Allogeneic Cd56+ Cell Infusion As A Bridge To Hematopoietic Stem Cell Transplantation In Relapsed/Refractory Acute Myeloid Leukemia: A Phase I Clinical Trial

Allogeneic Cd56+ Cell Infusion As A Bridge To Hematopoietic Stem Cell Transplantation In Relapsed/Refractory Acute Myeloid Leukemia: A Phase I Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Allogeneic Cd56+ Cell Infusion As A Bridge To Hematopoietic Stem Cell Transplantation In Relapsed/Refractory Acute Myeloid Leukemia: A Phase I Clinical Trial Amin Shahbaz ghasabeh, Amirhossein Izadpanah, Mehdi Bakhtiyaridovvombaygi, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7593855/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Mar, 2026 Read the published version in Cancer Immunology, Immunotherapy → Version 1 posted 11 You are reading this latest preprint version Abstract Background and purpose. Acute myeloid leukemia (AML) is an aggressive disease with suboptimal overall survival, especially in relapsed/refractory patients. The primary goal of salvage therapy in this patient is to achieve optimal disease control, thereby allowing the transition to hematopoietic stem cell transplantation (HSCT), which remains the only curative option for a subset of these patients. Allogeneic KIR ligand–mismatched CD56 + NK/NKT-like cells have demonstrated anti-leukemic activity and represent a promising platform for the development of novel cellular therapies. Study design. Relapsed/refractory non-M3 AML patients who were not HSCT candidates were included in this phase I clinical trial. Patients received the FLAG conditioning regimen followed by three escalating doses (1×10⁶, 3×10⁶, 5×10⁶ cells/kg) of CD56 + NK/NKT-like cells at 5-day intervals. Results. A total of 11 patients with a median age of 41.5 years were enrolled in the study. On average, they received three lines of prior chemotherapy and showed 18% blasts in their bone marrow. The infusion of CD56⁺ NK/NKT-like cells was safe, with no serious toxicity or graft-versus-host disease (GVHD) observed in any patient. Following this treatment protocol, five patients (45.4%) achieved complete remission (CR), with or without hematologic count recovery. Four of these patients (36.3%) underwent successful HSCT and remained event-free to the end of the follow-up period. Conclusion. Overall, these trials indicated that the FLAG regimen chemotherapy combined with allogeneic KIR ligand–mismatched CD56 + NK/NKT-like cell infusion is safe and may serve as an effective bridge to HSCT in 36.3% of patients with refractory/relapsed non-M3 AML. Acute myeloid leukemia Relapsed/refractory Natural killer cells CD56+ cells Hematopoietic stem cell transplantation Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Acute myeloid leukemia (AML) is an aggressive malignancy caused by clonal expansion of hematopoietic stem cells resulting from several genetic and/or epigenetic aberrations ( 1 , 2 ). For decades, intensive chemotherapy using agents like daunorubicin and cytarabine, followed by allogeneic hematopoietic stem cell transplantation (HSCT), was the standard treatment for adult AML patients who are at high risk of relapse. Recent innovations in cellular genetics and molecular biology have revolutionized the understanding of the biological basis of AML, resulting not only in improvements to standard chemotherapy but also in the development of a new wave of targeted therapies ( 3 ). Despite all therapeutic advances, overall outcomes remain poor, with a 5-year overall survival rate of only 22% for 60–69-year-old patients and < 5% for those ≥ 70 years ( 4 ). New therapeutic approaches have focused on achieving complete remission with no sign of minimal residual disease (MRD) to reduce relapse rates and increase overall survival ( 5 , 6 ). Immunotherapy represents a novel therapeutic strategy to achieve this goal by harnessing the immune system's capacity to identify and attack cancer cells through mechanisms distinct from those of chemotherapy drugs, including adoptive natural killer (NK) cell therapy. NK cells are important components of the innate immune system, defined by the coexpression of CD16 and CD56, providing the first line of defense against tumors and pathogens ( 7 ). NK cells exhibit cytotoxic activity against leukemia cells through perforin/granzyme-dependent mechanisms and the secretion of antitumor cytokines (e.g., IFN-γ and TNF-α). The enhanced cytotoxicity of autologous NK cells has been demonstrated to be correlated with prolonged leukemia-free survival ( 8 – 10 ). However, in AML patients, autologous NK cells have functional and quantitative defects with direct effect on their antitumor response, resulting in disease recurrence ( 11 ). These include a decrease in the number of NK cells, impaired cytotoxic function (decreased secretion of perforin and granzyme B), alterations in surface receptors (downregulation in NKG2D, NKp30, NKp44, and upregulation in NKG2A), and suppression by tumor cells and microenvironment through secretion of TGF-β and IL-10 ( 12 , 13 ). The presence of dysfunctional NK cells in AML patients provides a strong rationale for the implementation of NK cell-based immunotherapeutic approaches aimed at restoring antitumor activity, thereby contributing to improved clinical outcomes. Initially, pioneers Miller et al. conducted a study of adoptively infused haploidentical NK cells in combination with a high-dose cyclophosphamide and fludarabine regimen along with IL-2 in 19 high-risk AML patients with active disease; their results demonstrated a favorable safety and efficacy, with five patients achieving complete remission (CR) ( 14 ). In a recent study, a less toxic lymphocyte-depleting regimen was employed to minimize the unwanted side effects associated with high-intensity chemotherapy. Additionally, subcutaneous IL-2 injection was omitted to prevent the stimulation of regulatory T cells; instead, it was used for the ex vivo activation of NK cells. Using this protocol, 6 of 16 patients achieved CR or partial response (PR) to therapy, with five becoming eligible for HSCT, and three patients remained disease-free at the 3-year follow-up. In responding patients, clones with high-risk mutations became undetectable after treatment with NK cells. Overall, this study shows that NK cell therapy can induce a response in high-risk AML/MDS patients and suggests the use of haploidentical NK-cell infusions as a bridge to HSCT in these patients ( 15 ). In this phase I clinical trial, 11 patients with adult relapsed/refractory non-M3 AML received a FLAG conditioning regimen followed by three escalating doses of allogeneic CD56 + cells (1 × 10⁶, 3 × 10⁶, 5 × 10⁶ cells/kg) with five-day intervals. This study evaluated the safety and efficacy of this approach, with follow-up continued until the subsequent transplantation or chemotherapy. Using this protocol, 5 out of the 11 patients studied achieved complete remission. Among these patients, one experienced relapse after 2 months, and one achieved a negative MRD status. Four patients underwent hematopoietic cell transplantation. The 1-year overall survival rate was 36.4% (4/11 patients), as assessed from the date of CD56 + cell therapy. 2. Methods 2.1. Trial design, ethics, and registration This phase I, nonrandomized, open-label, single-center clinical trial was conducted at the Hematopoietic Stem Cell Transplantation and Cell Therapy Research Center, Taleghani Hospital, affiliated with Shahid Beheshti University of Medical Sciences. The study was approved by the institutional ethics committee (IR.SBMU.RETECH.REC.1402.153) and registered at the Iranian Registry of Clinical Trials (IRCT20230801058996N3) before the patients' recruitment. Written informed consent was obtained from all donors and recipients or their legal guardians, as per the Declaration of Helsinki. 2.2. Patient eligibility, inclusion, and exclusion criteria Adult patients (aged over 18 years) with relapsed/refractory non-M3 AML who were not eligible for allo-HSCT were enrolled based on predefined inclusion and exclusion criteria (Table 1 ). Relapsed or refractory disease is defined as either (i) disease recurrence (marrow blasts more than 5%) following an initial CR, or (ii) failure to achieve CR after at least two courses of induction chemotherapy ( 16 ). All enrolled patients had a Karnofsky performance scale index ≥ 70% and demonstrated adequate organ function at the time of enrollment (Table 1 ). All patients included in this study failed two or more prior chemotherapies and provided written informed consent for both treatment and data collection. Table 1 Trial inclusion and exclusion criteria Inclusion criteria Exclusion criteria 1. Age 18–70 years 1. Low-risk AML in CR 2. Signed informed consent form 2. Acute promyelocytic leukemia (M3) 3. Non-M3 AML (According to FAB classification) 3. Kidney, lung, liver, or heart failure (defined as creatinine > 2 mg/dL, oxygen saturation ≤ 93%, left ventricular ejection fraction < 50%, or bilirubin ≥ 3 mg/dL) 4. Relapsed or refractory AML 5. Karnofsky performance status index ranging from 70–100% 3. Symptoms of fluid retention (e.g., pleural effusion) 6. Absence of any other confirmed malignancies 4. Active autoimmune diseases 7. Lack of at least one of the “missing ligand”, including HLA-C allele groups (C1 or C2) or the HLA-Bw4 group 5. Liver cirrhosis 6. Concurrent participation in other clinical trials 7. Infections caused by hepatitis B, hepatitis C, or HIV 8. Uncontrolled bacterial infections 9. Any other conditions deemed life-threatening or potentially interfering with the study by the patient's physician FAB French-American-British, AML acute myeloid leukemia, CR complete remission, HIV human immunodeficiency virus 2.3. Donor selection Donor eligibility. Immediate relatives (parents, siblings, and offspring) aged 18 to 50 years were systematically screened to identify an appropriate allogeneic donor with a killer-cell immunoglobulin-like receptor (KIR) ligand mismatch in the graft-versus-host direction. In the presence of multiple potential donors, younger individuals were preferred. Inclusion and exclusion criteria. Donor selection was based on the following requirements: ( 1 ) body weight greater than 40 kg, and a peripheral blood white blood cell (WBC) count exceeding 5,000/µL; ( 2 ) negative serologic screening for active infections, including hepatitis B surface antigen (HBsAg) and antibody (HBsAb), hepatitis C virus antibody (HCV Ab), HIV antigen/antibody, cytomegalovirus (CMV Ab), Epstein‒Barr virus (EBV Ab), syphilis (VDRL), varicella-zoster virus (VZV Ab), herpes simplex virus (HSV Ab), and Toxoplasma antibody; and ( 3 ) absence of clinical symptoms and confirmation of general health based on comprehensive biochemical testing, including fasting blood sugar (FBS), urea, creatinine, serum transaminases (SGOT, SGPT), total and direct bilirubin, and alkaline phosphatase levels. In the end, eligible donors were selected for CD56 + cell donation. HLA and KIR typing. Patient and donor HLA typing for the C1/C2 groups and Bw4 epitopes, along with donor KIR genotyping, was performed via PCR-based methods. Donors are considered to mediate NK cell alloreactivity when their recipients lack one or more of the donor's inhibitory KIR ligands (HLA-C1, -C2, or -Bw4) (Table 2 ). 2.4. Preparation of CD56 + cell-enriched products CD56 + cell enrichment. Approximately two days prior to the first cell infusion, donors underwent a 4-hour leukapheresis session using the Spectra Optia apheresis system (Therumo BCT, USA). No adverse events or complications were reported during the collection process. The collected products were promptly transferred to the cell processing facility, where CD56⁺ cells were enriched via a single-step magnetic selection protocol with a Miltenyi Biotec CliniMACS Plus device and anti-human CD56 microbeads and reagents (Miltenyi Biotec, Germany) under good manufacturing practice (GMP)-compliant conditions. Following enrichment, the CD56⁺ cells were either fresh or cryopreserved for future administration. Quality control assessments. All the final CD56 + cell products were tested for sterility, mycoplasma contamination, and endotoxin levels before cryopreservation. Briefly, microbial contamination, including aerobic and anaerobic bacteria, yeast, and fungi, was assessed via the BACTEC 9120 microbial detection system, Mycoplasma was detected via PCR using the Mycoplasma Detection Kit (PrimerDesign genesig Kit, United Kingdom), and endotoxin levels were measured via the gel-clot limulus amoebocyte lysate (LAL) assay (Endosafe LAL kit, Charles River Endosafe, USA). Total nucleated cell counts were calculated using the Sysmex KX-21 hematology analyzer (Sysmex Corporation, Japan). Mononuclear cells were labeled with fluorochrome-conjugated antibodies (all from Miltenyi Biotec, Germany) against CD16, CD56, and CD3 in apheresis and enrichment products, and against CD14 and CD19 exclusively in the enrichment products, according to the manufacturer’s protocols. The samples were run on a MACS Quant 10 flow cytometer (Miltenyi Biotec, Germany), and the data were analyzed with FlowJo software version 10. Cell viability was assessed using 7-AAD (Miltenyi Biotec, Germany) cytofluorometric staining methods for freshly isolated cells or the trypan blue dye exclusion assay for thawed cells. Release criteria. The release criteria for the CD56 + cell product were as follows: cell viability > 90% for freshly infused cells or > 70% post thaw infusions, CD56 + cell content ≥ 90%, contaminating CD19⁺ B cells and CD14⁺ monocytes each < 5%, CD3 + CD56 − T cells < 1%, endotoxin < 0.125 EU/ml, absence of mycoplasma and negative microbiological test results. The products were distributed in sterile syringes or infusion bags under GMP conditions. 2.5. Treatment protocol Conditioning regimen. Seven days prior to CD56⁺ cell infusion (day − 7 to day − 2), patients received a five-day FLAG regimen to promote the immunosuppression and lymphodepletion necessary for the homeostatic proliferation of the infused allogeneic CD56⁺ cells. The regimen consisted of intravenous fludarabine (25 mg/m²/day), high-dose cytarabine (3 g/m²/day), and subcutaneous granulocyte colony-stimulating factor (G-CSF, 5 µg/kg/day). Fludarabine and cytarabine were administered from day − 7 to day − 3, whereas G-CSF was given from day − 6 to day − 2 (Fig. 1 ). Throughout the chemotherapy period, all patients received prophylactic antimicrobial therapy in accordance with the institutional protocols of Taleghani Hospital. CD56 + cell infusion. Two days after the final chemotherapy dose, on day 0, the patient received alloreactive CD56 + cells (1× 10⁶ cells/kg), followed by two additional escalating doses of CD56 + cells at five-day intervals, ranging from 3 × 10⁶ cells/kg to 5 × 10⁶ cells/kg (Fig. 1 ). In the first infusion, freshly purified CD56 + cells were administered, while subsequent infusions used cryopreserved aliquots (− 195°C) that were thawed and washed before infusion. Ten minutes prior to each infusion, either 10 mg of chlorphenamine or 100 mg of hydrocortisone was given intravenously to prevent allergic reactions. The patients did not receive exogenous cytokines or hematopoietic growth factors. 2.6. End Points Safety. The primary objectives of the study were to evaluate the feasibility and safety of administering escalating doses of allogeneic CD56⁺ cells following a FLAG conditioning regimen in adult patients with relapsed/refractory AML. Adverse events (AEs) were monitored and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The AE assessment was conducted at the start of the conditioning regimen and continued for 30 days after the final infusion of CD56 + cells. Efficacy. The secondary endpoints focused on evaluating the therapeutic efficacy of the infused CD56⁺ cells. Clinical responses were defined according to the Revised International Working Group (IWG) criteria for AML ( 17 ), including CR, CR with incomplete hematologic recovery (CRi), PR, stable disease (SD), and progressive disease (PD). Bone marrow (BM) examinations were performed on day + 28 and again between days 60 and 90. MRD was assessed using flow cytometry via AML-specific antibody panels. Survival assessments. Overall survival (OS) was defined as the time from CD56⁺ cell infusion to death from any cause, and event-free survival (EFS) was defined as the time to relapse, progression, or death. 2.7. Statistical analyses Descriptive statistics were employed to summarize the demographic characteristics, clinical features, and laboratory findings. All the statistical analyses were conducted via SPSS software version 25. Survival analysis was performed using the Kaplan–Meier method, with estimates reported alongside 95% confidence intervals (CIs) calculated using the Clopper–Pearson method. Comparisons between groups (e.g., responders versus non-responders, HSCT versus no HSCT) were performed using Fisher’s exact test. A P-value < 0.05 was considered statistically significant. 3. Results 3.1. Patient characteristics Between September 2022 and November 2023, 15 patients consented and were screened for eligibility, and 12 patients were enrolled in the present phase I trial. Among these patients, one individual developed a pulmonary infection prior to the initiation of CD56 + cell infusion and was consequently withdrawn from the study (Fig. 2 ). The median age of the patients was 41.5 years (range 22–64 years), with six male participants (Table 2 ). Eleven patients, three with refractory AML and eight with relapsed disease, proceeded to receive investigational therapy (Table 2 ). Patients had undergone a median of three lines of chemotherapy (range 2–5) for AML before receiving CD56 + cell therapy (Table 3 ). No patients had received prior allogenic stem cell transplantation. At enrollment, all patients who were in the active phase of the disease with BM demonstrated 7 to 91% (median 18%) blasts and were deemed ineligible for allogeneic HSCT due to progressive disease (Table 3 ). Three patients displayed cytogenetic abnormalities, one of whom had a favorable karyotype but still experienced disease relapse, while the remaining two had high-risk cytogenetic profiles. From the perspective of molecular characteristics, most patients had wild-type NPM1 exon 12, FLT-3 , or CEBPA mutations. One patient was positive for the KIT (D816V) mutation, and another patient was confirmed to be CEBPA positive. 3.2. CD56 + cell products The characteristics of the CD56 + cell products of the 11 patients included in this study are summarized in Tables 4 and 5 . All the manufacturing procedures were successful, with no failures reported during CD56⁺ cell production. The median leukapheresis volume obtained was 242 mL (199–318 mL). Before enrichment, the median number of mononuclear cells recovered from the leukapheresis product was 23×10 9 (19.8–30.4×10⁹), of which 120.1×10⁸ (43.4-155.3×10⁸) were CD56 − CD3 + T cells, 5.5×10⁸ (6.3–44.8×10⁸) were CD56 + CD3 − NK cells, and 7.0×10⁸ (3.0-18.9×10⁸) were CD56 + CD3 + NKT-like cells. Following immunomagnetic enrichment of CD56 + cells, the median number of mononuclear cells in the target bag decreased to 1.57×10⁹ (1.09–2.93×10⁹), with a median of 9.2×10⁶ (5.0–15.8×10⁶) CD56 − CD3 + T cells, 8.5×10⁸ (5.2–24.5×10⁸) CD56 + CD3 − NK cells, and 6.5×10⁸ (1.1–10.7×10⁸) CD56 + CD3 + NKT-like cells (Fig. 3 ). The mean purity of the final CD56⁺ product was 96.9% (90.6%–99.1%), with a CD56⁺ cell recovery rate of 59.3% (51.3%–77.0%). T-cell depletion achieved a median log reduction of -4.3 (3.66–4.48). The median viability of the freshly infused CD56⁺ cell products was 96.5% (94.8%–99.2%). Post-thaw analysis of cryopreserved products revealed excellent viability and recovery rates (median viability: 86%, median recovery: 82%). Table 2: Demographics and baseline disease characteristics of the patients patient Sex Age Diagnosis (FAB) Karyotype Genotype Recipient HLA I typing Donor KIR(mismtach) HLA typing (mismatch) Disease status before CD56 + cell infusion 1 F 64 M2 N/A N/A C1/C2, Bw6/Bw6 3DL1 -BW4 relapsed 2 F 31 M4 46XX, t(6:7), t(7:21) FLT3-IDT (neg), NPM (neg) C2/C2, Bw4/Bw6 2DL2 -C group 1 refractory 3 F 41 M4 46XX N/A C1/C1, Bw4/Bw4 2DL1 -C group 2 relapsed 4 F 28 M4 45XX,-7, t(3:3) FLT3-IDT (neg), IDH(1&2) (neg), NPM1 (neg), KIT(D816V) (pos), CEBPA (neg) C1/C1, Bw6/Bw6 2DL1 -C group 2 refractory 5 M 55 M1 N/A JAK2 (neg), FLT3-IDT (neg), NPM1 (neg), CEBPA (pos) C1/C2, Bw6/Bw6 3DL1 -BW4 relapsed 6 M 44 M4 46XY, NPM (neg), FLT3-IDH (neg) C1/C1, Bw6/Bw6 2DL1 -C group 2 relapsed 7 F 57 M0/M1 N/A N/A C1/C2, Bw6/Bw6 3DL1 -BW4 relapsed 8 M 44 M4 46XY BCR/ABL (neg), CEBPA (neg), NPM1exon12 (neg), FLT3 (neg) C2/C2, Bw4/Bw6 2DL2/3 -C group 1 refractory 9 M 29 M1 46XY BCR/ABL (neg), CEBPA (neg), NPM1exon12 (neg), FLT3 (neg) C1/C2, Bw6/Bw6 3DL1 -BW4 relapsed 10 M 22 M2 46XY, t(8:21) CEBPA (neg), NPM1exon12 (neg), FLT3 (neg), RUNX1-RUNX1T1 (pos) C2/C2, Bw4/Bw4 2DL2/3 -C group 1 relapsed 11 M 22 M0/M1 46XY C-Kit (neg), ABL/BCR (neg) C1/C2, Bw6/Bw6 3DL1 -BW4 relapsed M: male, F: female, FAB: French-American-British, N/A: not available, FLT3-ITD: FMS-like tyrosine kinase 3-internal tandem duplication, NPM1: Nucleophosmin 1, IDH2: isocitrate dehydrogenase, CEBPA: CCAAT/enhancer-binding protein alpha, AK2: Janus kinase 2, HLA: human leukocyte antigen, KIR: killer-cell immunoglobulin-like receptor, neg: negative, pos: positive Table 3 Baseline characteristics, chemotherapy history, cell infusion details, and clinical outcomes of the 11 study subjects who received CD56 + T-cell infusion patients BM Blasts at Diagnosis(%) prior chemotherapy lines BM Blasts changes after chemotherapy lines (%) BM Blasts before CD56 + cells infusion(%) CD56 + cell infusion doses(×10 6 /kg) BM Blasts at 1st follow up (%) MRD at 1st follow up (%) disease status BM Blasts at 2nd follow up(%) MRD at 2nd follow up(%) disease status at 2nd follow-up HCT after CD56 + cell Infusion One year follow-up Outcome 1st 2nd 3rd 4th 5th 1 N/A 3 + 7, HIDAC, VEN + VID N/A 18 1 3 5 N/A NA 25 25 PD N/A N/A N/A N Dead 2 30 5 + 2, HIDAC 30→10→7 7 1 3 5 N/A N/A 3 3 CR 4 4 CR Y Alive in CR 3 80 3 + 7, HIDAC, MEC 80→7→3→10 10 1 3 5 N/A N/A 1 < 1 CRi 80 - Relapsed N Dead 4 80 3 + 7, 5 + 2, FLAG, MEC,VEN + VID 80→12→76→10→6→23 23 1 3 5 N/A N/A 49 49 PD N/A N/A N/A N Dead 5 70 3 + 7, 3 + 7, HIDAC 70→20→5→2 21 1 3 5 5 5 2 1.7 CR 1 0.5 CR Y Alive in CR 6 85 3 + 7, HiDAC, azacitidin 85→1→2 90 1 3 5 N/A N/A 80 80 SD N/A N/A N/A N Dead 7 80 3 + 7, HIDAC, VEN + VID 80→40→2 80 1 3 5 N/A N/A 60 60 SD N/A N/A N/A N Dead 8 21 3 + 7, HIDAC 21→6→9 9 1 3 5 N/A N/A 30 30 PD N/A N/A N/A N Dead 9 81 3 + 7, HIDAC 81→9→1 15 1 3 5 5 5 1 0 CR with MRD neg HCT - HCT Y Alive in CR 10 45 3 + 7, HIDAC 45→6→12 12 1 3 5 N/A N/A 2 0.1 CR HCT - HCT Y Alive in CR 11 90 3 + 7, HIDAC, FLAG, MEC 90→1→6→1→30→91 91 1 3 5 N/A N/A 60 60 SD N/A N/A N/A N Dead BM: Bone Marrow, MRD: Minimal Residual Disease, HCT: Hematopoietic Cell Transplantation, 3 + 7: 3 days of an anthracycline + 7 days of cytarabine, HIDAC: High-Dose Cytarabine, VEN + VID: Venetoclax + Vidaza, 5 + 2: 5 days of cytarabine + 2 days of an anthracycline, FLAG: Fludarabine + Cytarabine (Ara-C) + G-CSF, MEC: Mitoxantrone + Etoposide + Cytarabine, CR: Complete Remission, CRI: Complete Remission with Incomplete hematologic recovery, CR with MRD-: Complete Remission with undetectable Minimal Residual Disease, PD: Progressive Disease, SD: Stable Disease, NA: Not Available/Not Applicable, Y/N: Yes/No, Table 4 Leukapheresis product characteristics Don1 Don 2 Don 3 Don 4 Don 5 Don 6 Don 7 Don 8 Don 9 Don 10 Don 11 Apheresis volume (ml) 400 380 350 350 370 350 300 400 380 420 390 TNC (× 10 9 ) 20.0 19.8 23.3 25.6 30.4 26.2 23.7 25.2 21.1 21.7 23.1 CD3 + CD56 − T cells (%) 21.7 43.8 40.5 60.7 37.0 49.5 50.7 47.9 63.4 58.1 59.4 Total T cells (× 10 8 ) 43.4 86.7 94.3 155.3 112.4 129.6 120.1 120.7 133.7 126.0 137.2 CD3 − CD56 + NK cells (%) 7.3 4.47 4.66 5.68 14.7 17.1 5.33 7.68 7.39 2.9 6.45 Total NK cells (× 10 8 ) 14.6 8.8 10.8 14.5 44.6 44.8 12.6 19.3 15.5 6.3 14.8 CD3 + CD56 + NKT cells (%) 1.6 5.39 5.44 6.53 1.43 1.23 8.0 2.13 3.32 6.8 9.30 Total NKT cells (× 10 8 ) 3.2 10.6 12.6 16.7 4.3 3.2 18.9 5.3 7.0 14.7 21.4 TNC: total nucleated cells, NK cell: natural killer cell, NKT cell: natural killer T-cell Table 5 Cell composition and viability of the final products after one-step CD56 + cell enrichment Don1 Don 2 Don 3 Don 4 Don 5 Don 6 Don 7 Don 8 Don 9 Don 10 Don 11 Final product volume (ml) 203 215 273 255 318 292 216 199 209 260 242 TNC (× 10 9 ) 1.09 1.25 1.82 1.63 2.93 2.6 1.78 1.57 1.35 1.55 1.99 Viability (%) * 96.2 95.7 97.4 98.1 98.7 96.5 94.8 99.2 96.2 96.0 97.3 CD3 + CD56 − T cells (%) 0.84 0.86 0.51 0.32 0.54 0.21 0.78 0.38 0.37 0.83 0.37 Total T cells (× 10 6 ) 9.1 10.7 9.2 5.2 15.8 5.4 13.8 5.9 4.9 12.8 7.3 CD3 − CD56 + NK cells (%) 66.0 45.7 51.9 40.0 66.5 94.4 36.9 71.4 62.9 33.8 38.2 Total NK cells (× 10 8 ) 7.1 5.7 9.4 6.5 19.4 24.5 6.5 11.2 8.4 5.2 7.6 CD56 dim CD16 + NK Cells (%) 52.5 35.5 48.9 35.9 52.0 91.5 24.9 53.6 52.6 14.2 25.0 CD56 bright CD16 − NK Cells (%) 3.72 3.71 2.84 3.43 9.75 1.15 6.51 8.56 6.52 3.39 7.62 CD3 + CD56 + NKT cells (%) 30.9 52.2 47.2 58.5 24.1 4.5 60.4 23.2 35.5 64.9 59.9 Total NKT cells (× 10 8 ) 3.3 6.5 8.5 9.5 7.0 1.1 10.7 3.6 4.7 10.0 11.9 CD19 + B cells (%) 1.75 0.74 0.35 1.17 4.19 0.41 1.31 0.48 0.96 3.39 0.95 CD14 + monocyte (%) 0.91 0.54 0.69 2.15 1.00 0.16 0.47 1.5 1.81 0.20 1.85 CD56 + cells recovery (%) a 58.4 62.9 76.4 51.3 54.0 53.4 54.6 60.1 58.2 72.3 53.9 T-cell depletion log b -2.68 -2.91 -3.01 -3.48 -2.85 -3.38 -2.94 -3.31 -3.44 -2.99 -3.27 a CD56⁺ cell recovery was calculated as follows: (CD56⁺ cells in the final product) / (CD56⁺ cells in the apheresis product×100). b T-cell depletion log was calculated as log₁₀ (T cells count in the final product / T cells count in the apheresis product). TNC: total nucleated cells, NK cell: natural killer cell, NKT cell: natural killer T-cell. 3.3. Safety Toxicity profiles were assessed in all 11 treated patients and are summarized in Table 4 . No dose-limiting toxicity (DLT) was observed; therefore, the highest administered dose, 5 × 10⁶ CD56⁺ cells/kg, was considered safe and well tolerated. Further dose escalation was not planned, as 5 × 10 6 cells/kg represented the technical limit of production from a single-step CD56 + cell selection approach. The infusions were well tolerated, with no grade 3–5 toxicities observed during CD56 + cell infusion or during the 30-day postinfusion monitoring period. Six patients experienced transient, grade 1 or 2 symptoms, including nausea, chills, headache, vomiting, and bone pain, which were considered to have a possible or imaginable causal relationship with CD56 + cell infusion (Table 4 ). We did not observe any symptoms or signs of graft-versus-host disease (GVHD), CRS, or neurotoxicity in any of the subjects. All other severe adverse events (SAEs; grade > 2), including neutropenia and febrile neutropenia, are common following standard conditioning chemotherapy and were accordingly considered unrelated to CD56 + cells in all patients. Table 6 Overall summary of nonhematologic adverse events related to therapy in the first 30 days after CD56 + cell infusion * Adverse event Total number(%) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Nausea 3(25%) 2 1 0 0 0 Chills 1(8%) 1 0 0 0 0 Headache 2(17%) 2 0 0 0 0 Vomiting 2(17%) 1 1 0 0 0 Sinus tachycardia 0(00%) 0 0 0 0 0 Bone pain 1(8%) 1 0 0 0 0 Pain in the extremity 0(00%) 0 0 0 0 0 Rash 0(00%) 0 0 0 0 0 Petechiae 0(00%) 0 0 0 0 0 dyspnea 0(00%) 0 0 0 0 0 The number and grade of adverse events that were considered to have a possible or probable causal relationship with treatment using alloreactive CD56⁺ cells. Patients with adverse events associated with conditioning regimens were excluded. 3.4. Clinical outcomes Following the administration of the FLAG chemotherapy regimen and CD56 + cell infusion, hematopoietic recovery was similar to what is typically observed after a standard chemotherapy cycle. The median time to absolute neutrophil count recovery (neutrophil count > 0.5 × 10⁶/µL for three consecutive days) was 23 days (range 17–42), and the median time to platelet recovery (platelet count > 20 × 10⁶/µL for three consecutive days) was 21 days (range 18–39). All patients underwent three planned infusions of CD56 + cells. On day 28 following cell infusion, five patients responded to therapy, four patients achieved CR (4/11, 36.3%), and one patient achieved CR with incomplete hematologic recovery(1/11, 9%). Among them, one patient (P.3) relapsed after two months and succumbed to PD. Additionally, one patient (P.9) achieved negative MRD accompanied by a reduction in blasts from 15% before CD56 + cell infusion to 1% after CD56 + cell infusion. Among the other six patients, three (27.2%) reached SD with a slight reduction in blast percentage, and three (27.2%) experienced PD with an increase in blasts. All six non-remission patients underwent further chemotherapy (Fig. 4 ). Four patients who achieved CR were deemed eligible for HSCT and had suitable stem cell donors. Among them, two patients (P.5 and P.9) received two additional doses of CD56 + cells as maintenance therapy before undergoing HSCT. These four patients (4/11, 36.3%) proceeded to allogeneic HSCT in sustained remission at days 57, 63, 128, and 92 post-CD56 + cell therapy and remained alive with their disease in CR. With a median follow-up of 6.5 months (range: 2–19), the one-year OS and event-free survival (EFS) rates for the entire cohort were both 36.4% (95% CI: 10.9–69.2). Patients who achieved CR/CRi had a significantly greater EFS of 80.0% (95% CI: 28.4–99.5) compared with 0% (95% CI: 0–45.9) in non-responders (p = 0.015). Furthermore, all patients who responded and underwent HSCT remained event-free at one year (100%, 95% CI: 39.8–100), whereas non-responders had an EFS of 0% (p = 0.005). Based on these findings, our trial protocol, which involves CD56 + cell infusion combined with FLAG regimen chemotherapy, was proposed as a successful bridge to HSCT in approximately 36.4% of patients by delivering an effective dose of CD56 + cells. 4. Discussion Although chemotherapy remains the standard first-line treatment for AML, approximately 10–40% of newly diagnosed patients do not respond to induction therapy and fail to achieve CR, a condition referred to as primary refractory AML. Additionally, among those who initially respond to chemotherapy, nearly half experience disease relapse. Together, chemotherapy resistance and relapse represent the major causes of mortality in AML patients ( 18 ). A variety of salvage regimens, ranging from non-intensive to intensive, have been utilized in refractory/relapsed AML patients to bridge patients to the only potentially curative option, allogeneic HSCT. However, most of these approaches are not promising due to the lack of sufficient efficacy or high toxicity ( 19 , 20 ). Immunotherapy based on adoptive CD56 + cells (including NK and NKT-like cells) has recently gained attention as a therapeutic strategy. The alloreactivity of NK cells due to donor and recipient KIR and HLA class I mismatch leads to GVL reactions, facilitating engraftment, and protecting against GVHD. Moreover, rapid NK cell recovery after HSCT is associated with improved outcomes, whereas impaired NK cell function is linked to disease progression ( 21 ). In the present study, we report the results of a phase I trial involving the infusion of KIR ligand–mismatched CD56 + NK/NKT-like cells in 11 adult patients with R/R non-M3 AML. Our findings, in line with previous studies, showed that administering CD56 + cells was safe, with no infusion-related adverse events, including CRS, neurotoxicity, or GVHD ( 22 – 26 ). Dose escalation was well tolerated, with a high dose of 5 × 10⁶ cells/kg, which represents the maximum yield routinely achievable from single-donor leukapheresis. Our results indicated that five patients achieved CR/CRi and became eligible for allogenic HSCT, and four of them proceeded to subsequent allogenic HSCT. At the censoring date, four patients were alive and in CR following transplantation. These clinical results suggest that this type of cell therapy may convert refractory or relapsed AML patients into transplant candidates, ultimately leading to a possible cure. Numerous clinical trials have investigated the adoptive transfer of NK cells following HSCT, either as a strategy to treat disease relapse or as a prophylactic (preemptive) approach to inhibit disease progression ( 27 – 30 ). In addition, clinical trials using allogeneic NK cells outside the transplantation setting to induce remission or as a consolidation therapy to extend CR have been conducted, and various manufacturing strategies and clinical protocols have been developed. Fehniger et al. ( 23 ) reported a phase I dose-escalation study in which 12 high-risk AML patients received cyclophosphamide and fludarabine followed by haploidentical NK cell infusions (CD3-CD56 + cells) primed with CTV-1 leukemia cell lysate in their first CR, showing no dose-limiting toxicities; notably, three patients achieved remarkably durable CR lasting 33–48 months after therapy. Björklund et al. ( 15 ) explored the safety and efficacy of IL-2-activated haploidentical NK cells in combination with lymphodepleting chemotherapy consisting of fludarabine, cyclophosphamide, and total lymphoid irradiation in 16 patients with refractory or relapsed AML/MDS who were ineligible for HSCT. In this trial, 37.5% of patients ( n = 6) responded to NK-cell therapy, 31.25% achieved CR, and five patients subsequently underwent allogeneic HSCT. Ciurea et al. ( 22 ) performed a phase I study in which 12 relapsed/refractory AML patients received FLAG chemotherapy plus six infusions of haploidentical NK cells expanded with engineered K562 feeder cells, achieving a CR rate of 58.3%, with a favorable safety profile, and five patients bridged to transplantation via the same donor. Conversely, a phase I study evaluating allogeneic expanded NK cell infusion on days 0 and + 7 following a conditioning regimen of fludarabine-endoxan in nine relapsed/refractory AML patients reported no CR achievement ( 24 ). Based on the aforementioned studies, to the best of our knowledge, we are conducting the first clinical trial to evaluate the safety and efficacy of infusing CD56 + cells, comprising a mixture of NK and NKT-like cells, with the specific goal of inducing remission and serving as a bridge to transplantation in adult patients with relapsed or refractory AML. Peripheral blood-derived NK cells, which have been widely utilized in clinical trials, are typically obtained from leukapheresis products as the initial source. To enrich the NK cell fraction, T cells can be depleted via anti-CD3 microbeads; however, this approach still results in a mixed population of other cell subsets, including residual B cells and monocytes. To reduce B-cell contamination further, anti-CD19 beads are subsequently applied. By sequential depletion of T cells followed by CD56 + cell enrichment, a highly purified NK cell population can be obtained, but this approach remains time-consuming and costly ( 31 ). An alternative and more cost-effective approach is the single-step selection of CD56 + cells, which yields a final cellular product containing a mixed population of NK and NKT-like cells ( 32 , 33 ). Both NK (CD3⁻CD56⁺) and NKT-like (CD3⁺CD56⁺) cells belong to the innate lymphocyte population. NKT-like cells constitute only a small fraction (0.2–8%) of total peripheral lymphocytes and are believed to play essential roles in various immune-related diseases, particularly cancer ( 34 ). Previous studies have shown a statistically significant correlation between the number of peripheral blood CD3⁺CD56⁺ NKT-like cells and a favorable prognosis in various types of cancer, including leukemia ( 34 ). Key cytotoxic molecules, such as perforin and granzyme levels, are significantly lower in patients with acute leukemia than in healthy individuals, indicating a CD3 + CD56 + cells functional impairment that may compromise their ability to eliminate leukemic clones ( 35 ). In preclinical models, CD8-expressing CD3 + CD56 + NKT cells have been shown to maintain GVL activity without exacerbating GVHD ( 36 ). Recent trial studies have provided evidence supporting the beneficial immunological effects of NKT-like cells in the setting of allogeneic allo-HSCT. Jaiswal et al. ( 32 ) demonstrated that the adoptive transfer of CD56-enriched donor lymphocytes, following posttransplant cyclophosphamide-based haploidentical HSCT, promotes robust reconstitution of NK cells and reduces the incidence of aGVHD. Kulkarni et al. ( 33 ) evaluated the therapeutic potential of a single dose of haploidentical CD56⁺ cell infusions (median total dose: 41.6 × 10⁶/kg, comprising 26.47 × 10⁶ CD3⁻CD56⁺ cells/kg and 13.36 × 10⁶ CD3⁺CD56⁺ cells/kg) as an adjunct to sequential transplantation in 14 patients with relapsed/refractory AML, aiming to selectively target and eradicate pretransplant MRD and thereby improve post-HSCT outcomes. In terms of efficacy, although definitive efficacy could not be demonstrated due to the small sample size and high nonrelapse mortality, the mean blast percentage decreased from 15.87% to 11.92% following cell infusion, and patients with greater MRD reduction appeared to achieve better disease control post-HSCT. These findings suggest that the transfer of NKT-like cells along with NK cells may represent a promising therapeutic strategy to enhance antileukemic immunity and improve the outcomes in AML patients. Interleukin-15 (IL-15) plays a crucial role in the differentiation, expansion, and survival of NK cells ( 37 ). Although Miller et al. ( 14 ) demonstrated that high-dose lymphodepleting regimens markedly increase endogenous IL-15 production, resulting in promoting the in vivo proliferation of NK cells. More recent data from Dr. Rezvani's group indicated that serum IL-15 levels remain largely unchanged following lymphodepleting or NK cell infusion ( 22 ). Notably, even at the lowest doses of infused NK cells, in vivo persistence and expansion of donor-derived NK cells were observed during the first week after the final infusion ( 22 ). Moreover, expansion of regulatory T cells following lymphodepleting therapy in the absence of IL-2 administration has also been reported, which may limit the engraftment and in vivo efficacy of donor-derived NK cells ( 15 ). One limitation of the current study is the absence of longitudinal tracking of donor CD56 + cell engraftment kinetics, cytokine profiles, and regulatory T-cell changes following chemotherapy. Thus, future studies are recommended to identify better factors influencing in vivo CD56 + cell expansion and functional activity. Finally, this study was not designed to characterize the features of CD56 + cell products before infusion. This limitation will be addressed in a planned phase 2 clinical trial through a comprehensive analysis of activating and inhibitory receptor expression on CD56 + cells. Conclusion Our findings demonstrated that multiple infusions of KIR ligand–mismatched CD56 + cells, intended to reduce disease burden and prepare patients with relapsed or refractory AML for subsequent allogeneic HSCT, were feasible and safe. Although tumor response was not the primary objective of this study, 4 out of 11 patients achieved remission and subsequently underwent transplantation, and all of them were alive in remission at the time of the last follow-up. However, despite these encouraging preliminary results, the findings should be interpreted with caution due to the limited sample size, which restricts the ability to draw definitive conclusions regarding clinical efficacy. Declarations Acknowledgments We sincerely thank our clinical collaborators for their expert care and unwavering dedication throughout this study. We are especially grateful to the patient volunteers and donors, whose trust and generous participation made this clinical trial possible. Author contributors E.R.: Conceptualization, Methodology, Data Analysis and, validation. A.SG. and A.I.: Investigation. A.H. and A.G.: Supervision and Validation A.I., M.S-A., and M.BD.: CD56⁺ cell collection and processing, Flow Cytometry, Molecular assays. M.BD. and M.SA.: Data Analysis. S.P., A.S., and H.RS.: Project Administration. M.BD., S.Y., and A.SG.: Writing – Review & Editing. All authors reviewed and approved the final version of the manuscript. Conflicts of interest The authors declare that they have no competing interests. Funding The authors received no financial support for the research, authorship, and publication of this article Data availability All the data generated or analyzed during this study have been included in this published article. Consent to participate All patients and donors provided written informed consent in accordance with the Declaration of Helsinki. References Lai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019;12(1):100. Pandolfi A, Barreyro L, Steidl U. Concise review: preleukemic stem cells: molecular biology and clinical implications of the precursors to leukemia stem cells. Stem Cells Transl Med. 2013;2(2):143-50. Forsberg M, Konopleva M. AML treatment: conventional chemotherapy and emerging novel agents. Trends Pharmacol Sci. 2024;45(5):430-48. Sasaki K, Ravandi F, Kadia TM, DiNardo CD, Short NJ, Borthakur G, et al. De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer. 2021;127(12):2049-61. Ball B, Stein EM. Which are the most promising targets for minimal residual disease-directed therapy in acute myeloid leukemia prior to allogeneic stem cell transplant? Haematologica. 2019;104(8):1521-31. Lichtenegger FS, Krupka C, Haubner S, Köhnke T, Subklewe M. Recent developments in immunotherapy of acute myeloid leukemia. J Hematol Oncol. 2017;10(1):142. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13(2):145-9. Tsirogianni M, Grigoriou E, Kapsimalli V, Dagla K, Stamouli M, Gkirkas K, et al. Natural killer cell cytotoxicity is a predictor of outcome for patients with high risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia treated with azacytidine. Leuk Lymphoma. 2019;60(10):2457-63. Lowdell MW, Craston R, Samuel D, Wood ME, O'Neill E, Saha V, et al. Evidence that continued remission in patients treated for acute leukaemia is dependent upon autologous natural killer cells. Br J Haematol. 2002;117(4):821-7. Torelli GF, Guarini A, Palmieri G, Breccia M, Vitale A, Santoni A, et al. Expansion of cytotoxic effectors with lytic activity against autologous blasts from acute myeloid leukaemia patients in complete haematological remission. Br J Haematol. 2002;116(2):299-307. Bakhtiyaridovvombaygi M, Yazdanparast S, Mikanik F, Izadpanah A, Parkhideh S, Shahbaz Ghasabeh A, et al. Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. Biomed Pharmacother. 2023;168:115718. Rahmani S, Yazdanpanah N, Rezaei N. Natural killer cells and acute myeloid leukemia: promises and challenges. Cancer Immunol Immunother. 2022;71(12):2849-67. D'Silva SZ, Singh M, Pinto AS. NK cell defects: implication in acute myeloid leukemia. Front Immunol. 2023;14:1112059. Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051-7. Björklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M, et al. Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML. Clin Cancer Res. 2018;24(8):1834-44. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-77. Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642-9. Li K, Du Y, Cai Y, Liu W, Lv Y, Huang B, et al. Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed/refractory acute myeloid leukemia. Leukemia. 2023;37(2):308-25. Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood. 2015;126(3):319-27. Wattad M, Weber D, Döhner K, Krauter J, Gaidzik VI, Paschka P, et al. Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia. 2017;31(6):1306-13. Xu J, Niu T. Natural killer cell-based immunotherapy for acute myeloid leukemia. J Hematol Oncol. 2020;13(1):167. Ciurea SO, Kongtim P, Srour S, Chen J, Soebbing D, Shpall E, et al. Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML. Am J Hematol. 2024;99(5):890-9. Fehniger TA, Miller JS, Stuart RK, Cooley S, Salhotra A, Curtsinger J, et al. A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2018;24(8):1581-9. Ahmadvand M, Barough MS, Barkhordar M, Faridfar A, Ghaderi A, Jalaeikhoo H, et al. Phase I non-randomized clinical trial of allogeneic natural killer cells infusion in acute myeloid leukemia patients. BMC Cancer. 2023;23(1):1090. Kottaridis PD, North J, Tsirogianni M, Marden C, Samuel ER, Jide-Banwo S, et al. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial. PLoS One. 2015;10(6):e0123416. Otegbeye F, Cooper B, Caimi P, Zamborsky K, Reese-Koc J, Hillian A, et al. A Phase I Study to Determine the Maximum Tolerated Dose of ex Vivo Expanded Natural Killer Cells Derived from Unrelated, HLA-Disparate Adult Donors. Transplant Cell Ther. 2022;28(5):250.e1-.e8. Mushtaq MU, Shahzad M, Shah AY, Chaudhary SG, Zafar MU, Anwar I, et al. Impact of natural killer cells on outcomes after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis. Front Immunol. 2022;13:1005031. Bednarski JJ, Zimmerman C, Berrien-Elliott MM, Foltz JA, Becker-Hapak M, Neal CC, et al. Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. Blood. 2022;139(11):1670-83. Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, et al. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant. 2014;20(5):696-704. Ciurea SO, Kongtim P, Soebbing D, Trikha P, Behbehani G, Rondon G, et al. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022;36(1):155-64. Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020;19(3):200-18. Jaiswal SR, Zaman S, Nedunchezhian M, Chakrabarti A, Bhakuni P, Ahmed M, et al. CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: A pilot study. Cytotherapy. 2017;19(4):531-42. Kulkarni U, Arunachalam AK, Palani HK, Nair RR, Balasundaram N, Venkatraman A, et al. Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia. Cell Transplant. 2023;32:9636897231198178. Min XY, Liu CF, Cao B, Zhang T, Yang X, Ma N, et al. Human CD3(+)CD56(+)NKT-like cells express a range of complement receptors and C3 activation has negative effects on these cell activity and effector function. Hum Immunol. 2021;82(9):625-33. Guo W, Xing C, Dong A, Lin X, Lin Y, Zhu B, et al. Numbers and cytotoxicities of CD3+CD56+ T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia. Cancer Biol Ther. 2013;14(10):916-21. Baker J, Verneris MR, Ito M, Shizuru JA, Negrin RS. Expansion of cytolytic CD8(+) natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon gamma production. Blood. 2001;97(10):2923-31. Huntington ND, Puthalakath H, Gunn P, Naik E, Michalak EM, Smyth MJ, et al. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol. 2007;8(8):856-63. Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Graphical Abstract Cite Share Download PDF Status: Published Journal Publication published 31 Mar, 2026 Read the published version in Cancer Immunology, Immunotherapy → Version 1 posted Editorial decision: Revision requested 19 Oct, 2025 Reviews received at journal 19 Oct, 2025 Reviews received at journal 05 Oct, 2025 Reviewers agreed at journal 02 Oct, 2025 Reviews received at journal 02 Oct, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers agreed at journal 20 Sep, 2025 Reviewers invited by journal 16 Sep, 2025 Editor assigned by journal 15 Sep, 2025 Submission checks completed at journal 15 Sep, 2025 First submitted to journal 11 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7593855","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":518995450,"identity":"b696203a-24eb-4e26-8e88-6969e2fdfcc4","order_by":0,"name":"Amin Shahbaz ghasabeh","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Science","correspondingAuthor":false,"prefix":"","firstName":"Amin","middleName":"Shahbaz","lastName":"ghasabeh","suffix":""},{"id":518995451,"identity":"5ec7c49f-4269-4681-83f9-136f84d90c2c","order_by":1,"name":"Amirhossein Izadpanah","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Amirhossein","middleName":"","lastName":"Izadpanah","suffix":""},{"id":518995452,"identity":"936dc4e3-0d14-4afe-bbf4-37de8941f2db","order_by":2,"name":"Mehdi Bakhtiyaridovvombaygi","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mehdi","middleName":"","lastName":"Bakhtiyaridovvombaygi","suffix":""},{"id":518995453,"identity":"8167ff36-2e0d-43e0-8661-eb1e269e1347","order_by":3,"name":"Mehrshad Seresht-Ahmadi","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mehrshad","middleName":"","lastName":"Seresht-Ahmadi","suffix":""},{"id":518995454,"identity":"d3ea4ebf-2e1f-410a-8f7e-4af9dc37936d","order_by":4,"name":"Sahar Parkhideh","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sahar","middleName":"","lastName":"Parkhideh","suffix":""},{"id":518995455,"identity":"cf39bf5f-6a15-4284-8f0b-a2d0d023c194","order_by":5,"name":"Hamide Rahmani Seraji","email":"","orcid":"","institution":"Taleghani Hospital, Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hamide","middleName":"Rahmani","lastName":"Seraji","suffix":""},{"id":518995456,"identity":"a477aba2-e3b1-4b4f-ba47-05850c92b67d","order_by":6,"name":"Abdollah Sabri","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Abdollah","middleName":"","lastName":"Sabri","suffix":""},{"id":518995457,"identity":"597274a6-0316-4118-b8ff-0c74a2a07fff","order_by":7,"name":"Somayeh Yazdanparast","email":"","orcid":"","institution":"Tarbiat Modares University","correspondingAuthor":false,"prefix":"","firstName":"Somayeh","middleName":"","lastName":"Yazdanparast","suffix":""},{"id":518995458,"identity":"62dfc8b9-c7e1-421f-b242-fbdadb1c45f7","order_by":8,"name":"Abbas Hajifathali","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Abbas","middleName":"","lastName":"Hajifathali","suffix":""},{"id":518995459,"identity":"8eee71d6-72e3-4832-ad8c-74591cbdada8","order_by":9,"name":"Ahmad Gharehbaghian","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Science","correspondingAuthor":false,"prefix":"","firstName":"Ahmad","middleName":"","lastName":"Gharehbaghian","suffix":""},{"id":518995460,"identity":"f5a70ebc-7efa-488a-9953-a0646c9d75b0","order_by":10,"name":"Elham Roshandel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYDACdh4oQwKIeRgs5EDsAw/waWFG1SJhDNaSQIqWxAYQB58Wfmbeg59uMNyTk5/d/OzBmwqJ9Plhhx8CbbGT023ArkWymS9ZOoeh2NjgzjFzwzlnJHI33k4zAGpJNjY7gF2LwWEeA6CWhMQNEglm0rxtQC2zE0BaDiRuw6HF/jCP8W+Qlvkz0r9J8/6TSDecnf4BrxYDZh4zsC0NN3KAtjRIJMhL5+C3ReIwj5l1jkGCscGNnDLJOcckDDdI5xQcSDDA7Rf+9h7j2zkVCXLyM9K3SbypsZGXn52++cOHCjs5XFqgzkNmH0AXIQjkG0hRPQpGwSgYBSMBAAB/hVi2Yqw5YAAAAABJRU5ErkJggg==","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Elham","middleName":"","lastName":"Roshandel","suffix":""}],"badges":[],"createdAt":"2025-09-11 16:38:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7593855/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7593855/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00262-025-04285-9","type":"published","date":"2026-03-31T16:00:07+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":92126327,"identity":"0c53e504-a097-43ca-b7fd-c4adc32af358","added_by":"auto","created_at":"2025-09-25 01:33:02","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1117656,"visible":true,"origin":"","legend":"","description":"","filename":"Finalversion.docx","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/33688feaae7d3bed82247eea.docx"},{"id":92127122,"identity":"f5aa4e20-bb6c-4bde-80ce-089e805919e6","added_by":"auto","created_at":"2025-09-25 01:41:03","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":11800,"visible":true,"origin":"","legend":"","description":"","filename":"d6eb8ade6f714311b27f7620c5fd6bf9.json","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/ecad53aacae643296f95e01a.json"},{"id":92126333,"identity":"e0e44cd3-51dd-44ca-bcd4-d0fa1fbadd2f","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":179290,"visible":true,"origin":"","legend":"","description":"","filename":"d6eb8ade6f714311b27f7620c5fd6bf91enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/5f864fa8a66fc45a318715ec.xml"},{"id":92126330,"identity":"90ef81f7-85ef-49e9-a479-62b3a9dd80eb","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114465,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/cf9ed0ef9edb6d35825a8d98.jpeg"},{"id":92127123,"identity":"055b6675-4a1c-477f-aa1d-f2533f9810ba","added_by":"auto","created_at":"2025-09-25 01:41:03","extension":"emf","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":37972,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.emf","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/9496485447dc7d08e9fcebac.emf"},{"id":92127126,"identity":"62e290d1-171f-4827-b578-00c3fcf1696f","added_by":"auto","created_at":"2025-09-25 01:41:03","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2742,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/94c8d7eb142cca2371b08128.jpeg"},{"id":92127125,"identity":"7fc79665-1e85-4080-8dd7-e19cbeb80ad0","added_by":"auto","created_at":"2025-09-25 01:41:03","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":337016,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/79bea64f68e25efc98a0775f.jpeg"},{"id":92127204,"identity":"41bae4e9-cc75-4b95-bb55-2366c3c915be","added_by":"auto","created_at":"2025-09-25 01:49:03","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":198795,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/20ed122b441ef9b7968af311.jpeg"},{"id":92126337,"identity":"9acf81ad-3fdd-4226-b750-022af2ba3b51","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68709,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/31885e84564dfb2b72d12863.png"},{"id":92127124,"identity":"832262e5-c58f-447a-8de6-1d203c204f44","added_by":"auto","created_at":"2025-09-25 01:41:03","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":26135,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/4a43d9cd1d77237db7f0b812.png"},{"id":92126343,"identity":"8501618e-6e7d-4127-8c64-30ab51ac2ef8","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":109278,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/fbec32bf4e4e57fdfad3ae92.png"},{"id":92126340,"identity":"480bd077-e79b-4a56-bbb7-85c15a60f39a","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1046,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/f4b85f52408ced4f48b1f363.png"},{"id":92126338,"identity":"20f668e2-e8e3-4bce-8512-1f633f8e8ba5","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":119600,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/c42e423d710ed1b7e4c8a8a4.png"},{"id":92126342,"identity":"f6611901-5961-4072-87ca-88bce14f19ed","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":30946,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/41424985f24b15a01d533c57.png"},{"id":92126344,"identity":"284b099b-9571-4444-8655-6f42b3c07c5a","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":174548,"visible":true,"origin":"","legend":"","description":"","filename":"d6eb8ade6f714311b27f7620c5fd6bf91structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/caed7157dcbea7c3693b8eef.xml"},{"id":92126348,"identity":"4803fec4-ae11-4e91-ac68-e6f556c205e1","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":182890,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/a7966b86a573a3c03cbb513d.html"},{"id":92127120,"identity":"bc6830b0-d38c-4989-9bc9-c2f3afcd60cb","added_by":"auto","created_at":"2025-09-25 01:41:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":163348,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic presentation of the treatment protocol. Approximately 200–300 mL of leukapheresis production was collected from related donors, and NK and NKT cells were isolated using a single-step positive selection process for CD56+ cells. Patients underwent standard FLAG chemotherapy at least seven days before the first CD56+ cell infusion. The chemotherapy regimen consisted of daily intravenous administration of fludarabine (25 mg/m²) and cytarabine (3 g/m²) from day –7 to day –3. G-CSF was administered subcutaneously at a dose of 5 µg/kg/day starting on day –6 and continued through day –2. Following a rest period of approximately two days, CD56+ cell infusions were initiated on day 0 and administered in three doses over two weeks. The first dose was infused fresh, while subsequent doses were cryopreserved and thawed before administration. Treatment response was evaluated at two time points: day +28 and between days +60 and +90. In selected patients who were candidates for hematopoietic stem cell transplantation, additional CD56+ cell infusions were administered in two doses prior to transplantation to reduce relapse risk.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/fbd0f66eb1943233e549dd2d.png"},{"id":92126336,"identity":"0898b0d4-35ad-4180-a919-52f92932e9b1","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":231172,"visible":true,"origin":"","legend":"\u003cp\u003eStudy enrollment summary.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/2f3e9e8aeb61b54c89dbe72e.png"},{"id":92126332,"identity":"bfdcc859-a72c-44a1-b606-cd20d7cd6c05","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":811570,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative dot plot of flow cytometry expression of CD3, CD56, and CD16 (A) before and (B) after CD56\u003csup\u003e+\u003c/sup\u003e cells selection.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/8f21a20f6adc3eb709fd7140.png"},{"id":92127121,"identity":"8b09179f-7460-480f-bb71-5194d94527bb","added_by":"auto","created_at":"2025-09-25 01:41:02","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":230698,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment Outcomes. (A) Swimmer plot showing treatment responses. (B) Kaplan-Meier analysis of overall survival among all patients receiving CD56⁺ cell therapy. Comparison of event-free survival (EFS) between patients who achieved complete remission (CR/CRi) and those who did not respond. Comparison of EFS between patients who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) and those who did not. Both overall survival and EFS were calculated from the start date of the first CD56⁺ cell infusion.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/05ba6242447afb5c174c499c.png"},{"id":106343586,"identity":"3bab5802-bb5d-4f24-a7a7-1319163d7ef9","added_by":"auto","created_at":"2026-04-07 16:06:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2908404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/3df650ca-9df2-453f-930e-1b4b0a181d72.pdf"},{"id":92126334,"identity":"88c82dc3-8780-4d8d-ad05-184d1c877d75","added_by":"auto","created_at":"2025-09-25 01:33:03","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":287210,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical Abstract\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7593855/v1/db1df7d86c2abc0971d912cc.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Allogeneic Cd56+ Cell Infusion As A Bridge To Hematopoietic Stem Cell Transplantation In Relapsed/Refractory Acute Myeloid Leukemia: A Phase I Clinical Trial","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAcute myeloid leukemia (AML) is an aggressive malignancy caused by clonal expansion of hematopoietic stem cells resulting from several genetic and/or epigenetic aberrations (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). For decades, intensive chemotherapy using agents like daunorubicin and cytarabine, followed by allogeneic hematopoietic stem cell transplantation (HSCT), was the standard treatment for adult AML patients who are at high risk of relapse. Recent innovations in cellular genetics and molecular biology have revolutionized the understanding of the biological basis of AML, resulting not only in improvements to standard chemotherapy but also in the development of a new wave of targeted therapies (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite all therapeutic advances, overall outcomes remain poor, with a 5-year overall survival rate of only 22% for 60\u0026ndash;69-year-old patients and \u0026lt;\u0026thinsp;5% for those\u0026thinsp;\u0026ge;\u0026thinsp;70 years (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNew therapeutic approaches have focused on achieving complete remission with no sign of minimal residual disease (MRD) to reduce relapse rates and increase overall survival (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Immunotherapy represents a novel therapeutic strategy to achieve this goal by harnessing the immune system's capacity to identify and attack cancer cells through mechanisms distinct from those of chemotherapy drugs, including adoptive natural killer (NK) cell therapy.\u003c/p\u003e\u003cp\u003eNK cells are important components of the innate immune system, defined by the coexpression of CD16 and CD56, providing the first line of defense against tumors and pathogens (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). NK cells exhibit cytotoxic activity against leukemia cells through perforin/granzyme-dependent mechanisms and the secretion of antitumor cytokines (e.g., IFN-γ and TNF-α). The enhanced cytotoxicity of autologous NK cells has been demonstrated to be correlated with prolonged leukemia-free survival (\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, in AML patients, autologous NK cells have functional and quantitative defects with direct effect on their antitumor response, resulting in disease recurrence (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). These include a decrease in the number of NK cells, impaired cytotoxic function (decreased secretion of perforin and granzyme B), alterations in surface receptors (downregulation in NKG2D, NKp30, NKp44, and upregulation in NKG2A), and suppression by tumor cells and microenvironment through secretion of TGF-β and IL-10 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The presence of dysfunctional NK cells in AML patients provides a strong rationale for the implementation of NK cell-based immunotherapeutic approaches aimed at restoring antitumor activity, thereby contributing to improved clinical outcomes.\u003c/p\u003e\u003cp\u003eInitially, pioneers Miller et al. conducted a study of adoptively infused haploidentical NK cells in combination with a high-dose cyclophosphamide and fludarabine regimen along with IL-2 in 19 high-risk AML patients with active disease; their results demonstrated a favorable safety and efficacy, with five patients achieving complete remission (CR) (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In a recent study, a less toxic lymphocyte-depleting regimen was employed to minimize the unwanted side effects associated with high-intensity chemotherapy. Additionally, subcutaneous IL-2 injection was omitted to prevent the stimulation of regulatory T cells; instead, it was used for the ex vivo activation of NK cells. Using this protocol, 6 of 16 patients achieved CR or partial response (PR) to therapy, with five becoming eligible for HSCT, and three patients remained disease-free at the 3-year follow-up. In responding patients, clones with high-risk mutations became undetectable after treatment with NK cells. Overall, this study shows that NK cell therapy can induce a response in high-risk AML/MDS patients and suggests the use of haploidentical NK-cell infusions as a bridge to HSCT in these patients (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn this phase I clinical trial, 11 patients with adult relapsed/refractory non-M3 AML received a FLAG conditioning regimen followed by three escalating doses of allogeneic CD56\u0026thinsp;+\u0026thinsp;cells (1 \u0026times; 10⁶, 3 \u0026times; 10⁶, 5 \u0026times; 10⁶ cells/kg) with five-day intervals. This study evaluated the safety and efficacy of this approach, with follow-up continued until the subsequent transplantation or chemotherapy. Using this protocol, 5 out of the 11 patients studied achieved complete remission. Among these patients, one experienced relapse after 2 months, and one achieved a negative MRD status. Four patients underwent hematopoietic cell transplantation. The 1-year overall survival rate was 36.4% (4/11 patients), as assessed from the date of CD56\u0026thinsp;+\u0026thinsp;cell therapy.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Trial design, ethics, and registration\u003c/h2\u003e\u003cp\u003eThis phase I, nonrandomized, open-label, single-center clinical trial was conducted at the Hematopoietic Stem Cell Transplantation and Cell Therapy Research Center, Taleghani Hospital, affiliated with Shahid Beheshti University of Medical Sciences. The study was approved by the institutional ethics committee (IR.SBMU.RETECH.REC.1402.153) and registered at the Iranian Registry of Clinical Trials (IRCT20230801058996N3) before the patients' recruitment. Written informed consent was obtained from all donors and recipients or their legal guardians, as per the Declaration of Helsinki.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Patient eligibility, inclusion, and exclusion criteria\u003c/h2\u003e\u003cp\u003eAdult patients (aged over 18 years) with relapsed/refractory non-M3 AML who were not eligible for allo-HSCT were enrolled based on predefined inclusion and exclusion criteria (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Relapsed or refractory disease is defined as either (i) disease recurrence (marrow blasts more than 5%) following an initial CR, or (ii) failure to achieve CR after at least two courses of induction chemotherapy (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). All enrolled patients had a Karnofsky performance scale index\u0026thinsp;\u0026ge;\u0026thinsp;70% and demonstrated adequate organ function at the time of enrollment (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All patients included in this study failed two or more prior chemotherapies and provided written informed consent for both treatment and data collection.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTrial inclusion and exclusion criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInclusion criteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExclusion criteria\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1. Age 18\u0026ndash;70 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1. Low-risk AML in CR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2. Signed informed consent form\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2. Acute promyelocytic leukemia (M3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3. Non-M3 AML (According to FAB classification)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3. Kidney, lung, liver, or heart failure (defined as creatinine\u0026thinsp;\u0026gt;\u0026thinsp;2 mg/dL, oxygen saturation\u0026thinsp;\u0026le;\u0026thinsp;93%, left ventricular ejection fraction\u0026thinsp;\u0026lt;\u0026thinsp;50%, or bilirubin\u0026thinsp;\u0026ge;\u0026thinsp;3 mg/dL)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4. Relapsed or refractory AML\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5. Karnofsky performance status index ranging from 70\u0026ndash;100%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3. Symptoms of fluid retention (e.g., pleural effusion)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6. Absence of any other confirmed malignancies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4. Active autoimmune diseases\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7. Lack of at least one of the \u0026ldquo;missing ligand\u0026rdquo;, including HLA-C allele groups (C1 or C2) or the HLA-Bw4 group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5. Liver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6. Concurrent participation in other clinical trials\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7. Infections caused by hepatitis B, hepatitis C, or HIV\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8. Uncontrolled bacterial infections\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9. Any other conditions deemed life-threatening or potentially interfering with the study by the patient's physician\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFAB French-American-British, AML acute myeloid leukemia, CR complete remission, HIV human immunodeficiency virus\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Donor selection\u003c/h2\u003e\u003cp\u003e\u003cb\u003eDonor eligibility.\u003c/b\u003e Immediate relatives (parents, siblings, and offspring) aged 18 to 50 years were systematically screened to identify an appropriate allogeneic donor with a killer-cell immunoglobulin-like receptor (KIR) ligand mismatch in the graft-versus-host direction. In the presence of multiple potential donors, younger individuals were preferred.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInclusion and exclusion criteria.\u003c/b\u003e Donor selection was based on the following requirements: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) body weight greater than 40 kg, and a peripheral blood white blood cell (WBC) count exceeding 5,000/\u0026micro;L; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) negative serologic screening for active infections, including hepatitis B surface antigen (HBsAg) and antibody (HBsAb), hepatitis C virus antibody (HCV Ab), HIV antigen/antibody, cytomegalovirus (CMV Ab), Epstein‒Barr virus (EBV Ab), syphilis (VDRL), varicella-zoster virus (VZV Ab), herpes simplex virus (HSV Ab), and Toxoplasma antibody; and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) absence of clinical symptoms and confirmation of general health based on comprehensive biochemical testing, including fasting blood sugar (FBS), urea, creatinine, serum transaminases (SGOT, SGPT), total and direct bilirubin, and alkaline phosphatase levels. In the end, eligible donors were selected for CD56\u003csup\u003e+\u003c/sup\u003e cell donation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eHLA and KIR typing.\u003c/b\u003e Patient and donor HLA typing for the C1/C2 groups and Bw4 epitopes, along with donor KIR genotyping, was performed via PCR-based methods. Donors are considered to mediate NK cell alloreactivity when their recipients lack one or more of the donor's inhibitory KIR ligands (HLA-C1, -C2, or -Bw4) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Preparation of CD56\u003csup\u003e+\u003c/sup\u003e cell-enriched products\u003c/h2\u003e\u003cp\u003e\u003cb\u003eCD56\u003c/b\u003e\u003csup\u003e\u003cb\u003e+\u003c/b\u003e\u003c/sup\u003e \u003cb\u003ecell enrichment.\u003c/b\u003e Approximately two days prior to the first cell infusion, donors underwent a 4-hour leukapheresis session using the Spectra Optia apheresis system (Therumo BCT, USA). No adverse events or complications were reported during the collection process. The collected products were promptly transferred to the cell processing facility, where CD56⁺ cells were enriched via a single-step magnetic selection protocol with a Miltenyi Biotec CliniMACS \u003csup\u003ePlus\u003c/sup\u003e device and anti-human CD56 microbeads and reagents (Miltenyi Biotec, Germany) under good manufacturing practice (GMP)-compliant conditions. Following enrichment, the CD56⁺ cells were either fresh or cryopreserved for future administration.\u003c/p\u003e\u003cp\u003e\u003cb\u003eQuality control assessments.\u003c/b\u003e All the final CD56\u003csup\u003e+\u003c/sup\u003e cell products were tested for sterility, mycoplasma contamination, and endotoxin levels before cryopreservation. Briefly, microbial contamination, including aerobic and anaerobic bacteria, yeast, and fungi, was assessed via the BACTEC 9120 microbial detection system, Mycoplasma was detected via PCR using the Mycoplasma Detection Kit (PrimerDesign genesig Kit, United Kingdom), and endotoxin levels were measured via the gel-clot limulus amoebocyte lysate (LAL) assay (Endosafe LAL kit, Charles River Endosafe, USA). Total nucleated cell counts were calculated using the Sysmex KX-21 hematology analyzer (Sysmex Corporation, Japan).\u003c/p\u003e\u003cp\u003eMononuclear cells were labeled with fluorochrome-conjugated antibodies (all from Miltenyi Biotec, Germany) against CD16, CD56, and CD3 in apheresis and enrichment products, and against CD14 and CD19 exclusively in the enrichment products, according to the manufacturer\u0026rsquo;s protocols. The samples were run on a MACS Quant 10 flow cytometer (Miltenyi Biotec, Germany), and the data were analyzed with FlowJo software version 10.\u003c/p\u003e\u003cp\u003eCell viability was assessed using 7-AAD (Miltenyi Biotec, Germany) cytofluorometric staining methods for freshly isolated cells or the trypan blue dye exclusion assay for thawed cells.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRelease criteria.\u003c/b\u003e The release criteria for the CD56\u003csup\u003e+\u003c/sup\u003e cell product were as follows: cell viability\u0026thinsp;\u0026gt;\u0026thinsp;90% for freshly infused cells or \u0026gt;\u0026thinsp;70% post thaw infusions, CD56\u003csup\u003e+\u003c/sup\u003e cell content\u0026thinsp;\u0026ge;\u0026thinsp;90%, contaminating CD19⁺ B cells and CD14⁺ monocytes each \u0026lt;\u0026thinsp;5%, CD3\u003csup\u003e+\u003c/sup\u003eCD56\u003csup\u003e\u0026minus;\u003c/sup\u003e T cells\u0026thinsp;\u0026lt;\u0026thinsp;1%, endotoxin\u0026thinsp;\u0026lt;\u0026thinsp;0.125 EU/ml, absence of mycoplasma and negative microbiological test results. The products were distributed in sterile syringes or infusion bags under GMP conditions.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Treatment protocol\u003c/h2\u003e\u003cp\u003e\u003cb\u003eConditioning regimen.\u003c/b\u003e Seven days prior to CD56⁺ cell infusion (day \u0026minus;\u0026thinsp;7 to day \u0026minus;\u0026thinsp;2), patients received a five-day FLAG regimen to promote the immunosuppression and lymphodepletion necessary for the homeostatic proliferation of the infused allogeneic CD56⁺ cells. The regimen consisted of intravenous fludarabine (25 mg/m\u0026sup2;/day), high-dose cytarabine (3 g/m\u0026sup2;/day), and subcutaneous granulocyte colony-stimulating factor (G-CSF, 5 \u0026micro;g/kg/day). Fludarabine and cytarabine were administered from day \u0026minus;\u0026thinsp;7 to day \u0026minus;\u0026thinsp;3, whereas G-CSF was given from day \u0026minus;\u0026thinsp;6 to day \u0026minus;\u0026thinsp;2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Throughout the chemotherapy period, all patients received prophylactic antimicrobial therapy in accordance with the institutional protocols of Taleghani Hospital.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCD56\u0026thinsp;+\u0026thinsp;cell infusion. Two days after the final chemotherapy dose, on day 0, the patient received alloreactive CD56\u0026thinsp;+\u0026thinsp;cells (1\u0026times; 10⁶ cells/kg), followed by two additional escalating doses of CD56\u0026thinsp;+\u0026thinsp;cells at five-day intervals, ranging from 3 \u0026times; 10⁶ cells/kg to 5 \u0026times; 10⁶ cells/kg (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the first infusion, freshly purified CD56\u0026thinsp;+\u0026thinsp;cells were administered, while subsequent infusions used cryopreserved aliquots (\u0026minus;\u0026thinsp;195\u0026deg;C) that were thawed and washed before infusion. Ten minutes prior to each infusion, either 10 mg of chlorphenamine or 100 mg of hydrocortisone was given intravenously to prevent allergic reactions. The patients did not receive exogenous cytokines or hematopoietic growth factors.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6. End Points\u003c/h2\u003e\u003cp\u003e\u003cb\u003eSafety.\u003c/b\u003e The primary objectives of the study were to evaluate the feasibility and safety of administering escalating doses of allogeneic CD56⁺ cells following a FLAG conditioning regimen in adult patients with relapsed/refractory AML. Adverse events (AEs) were monitored and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The AE assessment was conducted at the start of the conditioning regimen and continued for 30 days after the final infusion of CD56\u003csup\u003e+\u003c/sup\u003e cells.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEfficacy.\u003c/b\u003e The secondary endpoints focused on evaluating the therapeutic efficacy of the infused CD56⁺ cells. Clinical responses were defined according to the Revised International Working Group (IWG) criteria for AML (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), including CR, CR with incomplete hematologic recovery (CRi), PR, stable disease (SD), and progressive disease (PD). Bone marrow (BM) examinations were performed on day\u0026thinsp;+\u0026thinsp;28 and again between days 60 and 90. MRD was assessed using flow cytometry via AML-specific antibody panels.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSurvival assessments.\u003c/b\u003e Overall survival (OS) was defined as the time from CD56⁺ cell infusion to death from any cause, and event-free survival (EFS) was defined as the time to relapse, progression, or death.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.7. Statistical analyses\u003c/h2\u003e\u003cp\u003eDescriptive statistics were employed to summarize the demographic characteristics, clinical features, and laboratory findings. All the statistical analyses were conducted via SPSS software version 25. Survival analysis was performed using the Kaplan\u0026ndash;Meier method, with estimates reported alongside 95% confidence intervals (CIs) calculated using the Clopper\u0026ndash;Pearson method. Comparisons between groups (e.g., responders versus non-responders, HSCT versus no HSCT) were performed using Fisher\u0026rsquo;s exact test. A P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Patient characteristics\u003c/h2\u003e\u003cp\u003eBetween September 2022 and November 2023, 15 patients consented and were screened for eligibility, and 12 patients were enrolled in the present phase I trial. Among these patients, one individual developed a pulmonary infection prior to the initiation of CD56\u0026thinsp;+\u0026thinsp;cell infusion and was consequently withdrawn from the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median age of the patients was 41.5 years (range 22\u0026ndash;64 years), with six male participants (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Eleven patients, three with refractory AML and eight with relapsed disease, proceeded to receive investigational therapy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Patients had undergone a median of three lines of chemotherapy (range 2\u0026ndash;5) for AML before receiving CD56\u003csup\u003e+\u003c/sup\u003e cell therapy (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No patients had received prior allogenic stem cell transplantation. At enrollment, all patients who were in the active phase of the disease with BM demonstrated 7 to 91% (median 18%) blasts and were deemed ineligible for allogeneic HSCT due to progressive disease (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThree patients displayed cytogenetic abnormalities, one of whom had a favorable karyotype but still experienced disease relapse, while the remaining two had high-risk cytogenetic profiles. From the perspective of molecular characteristics, most patients had wild-type \u003cem\u003eNPM1\u003c/em\u003e exon 12, \u003cem\u003eFLT-3\u003c/em\u003e, or \u003cem\u003eCEBPA\u003c/em\u003e mutations. One patient was positive for the \u003cem\u003eKIT (D816V)\u003c/em\u003e mutation, and another patient was confirmed to be \u003cem\u003eCEBPA\u003c/em\u003e positive.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.2. CD56\u003csup\u003e+\u003c/sup\u003e cell products\u003c/h2\u003e\u003cp\u003eThe characteristics of the CD56\u003csup\u003e+\u003c/sup\u003e cell products of the 11 patients included in this study are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. All the manufacturing procedures were successful, with no failures reported during CD56⁺ cell production. The median leukapheresis volume obtained was 242 mL (199\u0026ndash;318 mL). Before enrichment, the median number of mononuclear cells recovered from the leukapheresis product was 23\u0026times;10\u003csup\u003e9\u003c/sup\u003e (19.8\u0026ndash;30.4\u0026times;10⁹), of which 120.1\u0026times;10⁸ (43.4-155.3\u0026times;10⁸) were CD56\u003csup\u003e\u0026minus;\u003c/sup\u003eCD3\u003csup\u003e+\u003c/sup\u003e T cells, 5.5\u0026times;10⁸ (6.3\u0026ndash;44.8\u0026times;10⁸) were CD56\u003csup\u003e+\u003c/sup\u003eCD3\u003csup\u003e\u0026minus;\u003c/sup\u003e NK cells, and 7.0\u0026times;10⁸ (3.0-18.9\u0026times;10⁸) were CD56\u003csup\u003e+\u003c/sup\u003eCD3\u003csup\u003e+\u003c/sup\u003e NKT-like cells. Following immunomagnetic enrichment of CD56\u003csup\u003e+\u003c/sup\u003e cells, the median number of mononuclear cells in the target bag decreased to 1.57\u0026times;10⁹ (1.09\u0026ndash;2.93\u0026times;10⁹), with a median of 9.2\u0026times;10⁶ (5.0\u0026ndash;15.8\u0026times;10⁶) CD56\u003csup\u003e\u0026minus;\u003c/sup\u003eCD3\u003csup\u003e+\u003c/sup\u003e T cells, 8.5\u0026times;10⁸ (5.2\u0026ndash;24.5\u0026times;10⁸) CD56\u003csup\u003e+\u003c/sup\u003eCD3\u003csup\u003e\u0026minus;\u003c/sup\u003e NK cells, and 6.5\u0026times;10⁸ (1.1\u0026ndash;10.7\u0026times;10⁸) CD56\u003csup\u003e+\u003c/sup\u003eCD3\u003csup\u003e+\u003c/sup\u003e NKT-like cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The mean purity of the final CD56⁺ product was 96.9% (90.6%\u0026ndash;99.1%), with a CD56⁺ cell recovery rate of 59.3% (51.3%\u0026ndash;77.0%). T-cell depletion achieved a median log reduction of -4.3 (3.66\u0026ndash;4.48). The median viability of the freshly infused CD56⁺ cell products was 96.5% (94.8%\u0026ndash;99.2%). Post-thaw analysis of cryopreserved products revealed excellent viability and recovery rates (median viability: 86%, median recovery: 82%).\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e Demographics and baseline disease characteristics of the patients\u003c/p\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003epatient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDiagnosis (FAB)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eKaryotype\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGenotype\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRecipient HLA I typing\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eDonor KIR(mismtach)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHLA typing (mismatch)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDisease status before CD56\u003csup\u003e+\u003c/sup\u003e cell infusion\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C2, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-BW4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XX, t(6:7), t(7:21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eFLT3-IDT\u003c/em\u003e (neg), \u003cem\u003eNPM\u003c/em\u003e (neg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC2/C2, Bw4/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2DL2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-C group 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erefractory\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C1, Bw4/Bw4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-C group 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45XX,-7, t(3:3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eFLT3-IDT\u003c/em\u003e (neg), \u003cem\u003eIDH(1\u0026amp;2)\u003c/em\u003e (neg), \u003cem\u003eNPM1\u003c/em\u003e(neg), \u003cem\u003eKIT(D816V)\u003c/em\u003e (pos), \u003cem\u003eCEBPA\u003c/em\u003e(neg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C1, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-C group 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erefractory\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eJAK2\u003c/em\u003e (neg), \u003cem\u003eFLT3-IDT\u003c/em\u003e (neg), \u003cem\u003eNPM1\u003c/em\u003e(neg), \u003cem\u003eCEBPA\u003c/em\u003e (pos)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C2, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-BW4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XY,\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eNPM\u003c/em\u003e (neg), \u003cem\u003eFLT3-IDH\u003c/em\u003e (neg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C1, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-C group 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM0/M1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C2, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-BW4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eBCR/ABL\u003c/em\u003e (neg), \u003cem\u003eCEBPA\u003c/em\u003e (neg), \u003cem\u003eNPM1exon12\u003c/em\u003e (neg), \u003cem\u003eFLT3\u003c/em\u003e(neg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC2/C2, Bw4/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2DL2/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-C group 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erefractory\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eBCR/ABL\u003c/em\u003e (neg), \u003cem\u003eCEBPA\u003c/em\u003e (neg), \u003cem\u003eNPM1exon12\u003c/em\u003e (neg), \u003cem\u003eFLT3\u003c/em\u003e (neg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C2, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-BW4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XY, t(8:21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eCEBPA\u003c/em\u003e(neg), \u003cem\u003eNPM1exon12\u003c/em\u003e (neg), \u003cem\u003eFLT3\u003c/em\u003e (neg), \u003cem\u003eRUNX1-RUNX1T1\u003c/em\u003e(pos)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC2/C2, Bw4/Bw4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2DL2/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-C group 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM0/M1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46XY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eC-Kit\u003c/em\u003e (neg), \u003cem\u003eABL/BCR\u003c/em\u003e (neg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eC1/C2, Bw6/Bw6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3DL1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-BW4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003erelapsed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eM: male, F: female, FAB: French-American-British, N/A: not available, FLT3-ITD: FMS-like tyrosine kinase 3-internal tandem duplication, NPM1: Nucleophosmin 1, IDH2: isocitrate dehydrogenase, CEBPA: CCAAT/enhancer-binding protein alpha, AK2: Janus kinase 2, HLA: human leukocyte antigen, KIR: killer-cell immunoglobulin-like receptor, neg: negative, pos: positive\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics, chemotherapy history, cell infusion details, and clinical outcomes of the 11 study subjects who received CD56\u003csup\u003e+\u003c/sup\u003e T-cell infusion\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"18\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epatients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBM Blasts at\u003c/p\u003e\u003cp\u003eDiagnosis(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eprior chemotherapy lines\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBM Blasts changes after chemotherapy lines (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBM Blasts before CD56\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ecells infusion(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e\u003cp\u003eCD56\u003csup\u003e+\u003c/sup\u003e cell infusion doses(\u0026times;10\u003csup\u003e6\u003c/sup\u003e/kg)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBM Blasts at 1st\u003c/p\u003e\u003cp\u003efollow up (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMRD at 1st\u003c/p\u003e\u003cp\u003efollow up (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003edisease status\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBM Blasts at 2nd\u003c/p\u003e\u003cp\u003efollow up(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMRD at 2nd\u003c/p\u003e\u003cp\u003efollow up(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003edisease status\u003c/p\u003e\u003cp\u003eat 2nd follow-up\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c17\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHCT after CD56\u003csup\u003e+\u003c/sup\u003e cell\u003c/p\u003e\u003cp\u003eInfusion\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c18\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOne\u003c/p\u003e\u003cp\u003eyear follow-up\u003c/p\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1st\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2nd\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3rd\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4th\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e5th\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC, VEN\u0026thinsp;+\u0026thinsp;VID\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u0026thinsp;+\u0026thinsp;2, HIDAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30\u0026rarr;10\u0026rarr;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eAlive in CR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC, MEC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80\u0026rarr;7\u0026rarr;3\u0026rarr;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCRi\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eRelapsed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, 5\u0026thinsp;+\u0026thinsp;2, FLAG, MEC,VEN\u0026thinsp;+\u0026thinsp;VID\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80\u0026rarr;12\u0026rarr;76\u0026rarr;10\u0026rarr;6\u0026rarr;23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, 3\u0026thinsp;+\u0026thinsp;7, HIDAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70\u0026rarr;20\u0026rarr;5\u0026rarr;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eAlive in CR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HiDAC, azacitidin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85\u0026rarr;1\u0026rarr;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC, VEN\u0026thinsp;+\u0026thinsp;VID\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80\u0026rarr;40\u0026rarr;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21\u0026rarr;6\u0026rarr;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81\u0026rarr;9\u0026rarr;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCR with MRD\u003csup\u003eneg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eHCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eHCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eAlive in CR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45\u0026rarr;6\u0026rarr;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eHCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eHCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eAlive in CR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u0026thinsp;+\u0026thinsp;7, HIDAC, FLAG, MEC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e90\u0026rarr;1\u0026rarr;6\u0026rarr;1\u0026rarr;30\u0026rarr;91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"18\"\u003eBM: Bone Marrow, MRD: Minimal Residual Disease, HCT: Hematopoietic Cell Transplantation, 3\u0026thinsp;+\u0026thinsp;7: 3 days of an anthracycline\u0026thinsp;+\u0026thinsp;7 days of cytarabine, HIDAC: High-Dose Cytarabine, VEN\u0026thinsp;+\u0026thinsp;VID: Venetoclax\u0026thinsp;+\u0026thinsp;Vidaza, 5\u0026thinsp;+\u0026thinsp;2: 5 days of cytarabine\u0026thinsp;+\u0026thinsp;2 days of an anthracycline, FLAG: Fludarabine\u0026thinsp;+\u0026thinsp;Cytarabine (Ara-C)\u0026thinsp;+\u0026thinsp;G-CSF, MEC: Mitoxantrone\u0026thinsp;+\u0026thinsp;Etoposide\u0026thinsp;+\u0026thinsp;Cytarabine, CR: Complete Remission, CRI: Complete Remission with Incomplete hematologic recovery, CR with MRD-: Complete Remission with undetectable Minimal Residual Disease, PD: Progressive Disease, SD: Stable Disease, NA: Not Available/Not Applicable, Y/N: Yes/No,\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLeukapheresis product characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDon1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDon 2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDon 3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDon 4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDon 5\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDon 6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eDon 7\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDon 8\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDon 9\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDon 10\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDon 11\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eApheresis volume (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e380\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e350\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e350\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e370\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e350\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e300\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e380\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e420\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e390\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNC (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e25.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e26.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e23.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e25.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e21.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e21.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e23.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3\u003csup\u003e+\u003c/sup\u003eCD56\u003csup\u003e\u0026minus;\u003c/sup\u003e T cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e60.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e49.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e50.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e47.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e63.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e58.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e59.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal T cells (\u0026times; 10\u003csup\u003e8\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e94.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e155.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e112.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e129.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e120.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e120.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e133.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e126.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e137.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3\u003csup\u003e\u0026minus;\u003c/sup\u003eCD56\u003csup\u003e+\u003c/sup\u003eNK cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e17.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e7.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e7.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e6.45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal NK cells (\u0026times; 10\u003csup\u003e8\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e44.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e44.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e19.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e15.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3\u003csup\u003e+\u003c/sup\u003eCD56\u003csup\u003e+\u003c/sup\u003eNKT cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e3.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e9.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal NKT cells (\u0026times; 10\u003csup\u003e8\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e18.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e14.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e21.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"12\"\u003eTNC: total nucleated cells, NK cell: natural killer cell, NKT cell: natural killer T-cell\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCell composition and viability of the final products after one-step CD56\u003csup\u003e+\u003c/sup\u003e cell enrichment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDon1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDon 2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDon 3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDon 4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDon 5\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDon 6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eDon 7\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDon 8\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDon 9\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDon 10\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDon 11\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFinal product volume (ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e203\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e215\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e273\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e255\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e292\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e216\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e199\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e209\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e260\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e242\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNC (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViability (%)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e97.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e98.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e98.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e96.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e94.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e99.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e96.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e96.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e97.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3\u003csup\u003e+\u003c/sup\u003eCD56\u003csup\u003e\u0026minus;\u003c/sup\u003e T cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal T cells (\u0026times; 10\u003csup\u003e6\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e13.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e4.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e12.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3\u003csup\u003e\u0026minus;\u003c/sup\u003eCD56\u003csup\u003e+\u003c/sup\u003eNK cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e40.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e66.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e94.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e36.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e71.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e62.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e33.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e38.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal NK cells (\u0026times; 10\u003csup\u003e8\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e19.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e7.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD56\u003csup\u003edim\u003c/sup\u003eCD16\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNK Cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e52.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e91.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e24.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e53.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e52.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e14.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e25.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD56\u003csup\u003ebright\u003c/sup\u003eCD16\u003csup\u003e\u0026minus;\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNK Cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e6.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e7.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3\u003csup\u003e+\u003c/sup\u003eCD56\u003csup\u003e+\u003c/sup\u003eNKT cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e58.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e60.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e23.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e35.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e64.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e59.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal NKT cells (\u0026times; 10\u003csup\u003e8\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e4.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e11.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD19\u003csup\u003e+\u003c/sup\u003e B cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD14\u003csup\u003e+\u003c/sup\u003e monocyte (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD56\u0026thinsp;+\u0026thinsp;cells recovery (%)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e51.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e54.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e60.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e58.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e72.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e53.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT-cell depletion log\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-3.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-3.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-2.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-3.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-3.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-2.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-3.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e CD56⁺ cell recovery was calculated as follows: (CD56⁺ cells in the final product) / (CD56⁺ cells in the apheresis product\u0026times;100).\u003c/p\u003e\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e T-cell depletion log was calculated as log₁₀ (T cells count in the final product / T cells count in the apheresis product).\u003c/p\u003e\u003cp\u003eTNC: total nucleated cells, NK cell: natural killer cell, NKT cell: natural killer T-cell.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Safety\u003c/h2\u003e\u003cp\u003eToxicity profiles were assessed in all 11 treated patients and are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. No dose-limiting toxicity (DLT) was observed; therefore, the highest administered dose, 5 \u0026times; 10⁶ CD56⁺ cells/kg, was considered safe and well tolerated. Further dose escalation was not planned, as 5 \u0026times; 10\u003csup\u003e6\u003c/sup\u003e cells/kg represented the technical limit of production from a single-step CD56\u003csup\u003e+\u003c/sup\u003e cell selection approach. The infusions were well tolerated, with no grade 3\u0026ndash;5 toxicities observed during CD56\u003csup\u003e+\u003c/sup\u003e cell infusion or during the 30-day postinfusion monitoring period. Six patients experienced transient, grade 1 or 2 symptoms, including nausea, chills, headache, vomiting, and bone pain, which were considered to have a possible or imaginable causal relationship with CD56\u003csup\u003e+\u003c/sup\u003e cell infusion (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). We did not observe any symptoms or signs of graft-versus-host disease (GVHD), CRS, or neurotoxicity in any of the subjects. All other severe adverse events (SAEs; grade\u0026thinsp;\u0026gt;\u0026thinsp;2), including neutropenia and febrile neutropenia, are common following standard conditioning chemotherapy and were accordingly considered unrelated to CD56\u0026thinsp;+\u0026thinsp;cells in all patients.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOverall summary of nonhematologic adverse events related to therapy in the first 30 days after CD56\u0026thinsp;+\u0026thinsp;cell infusion\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse event\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal number(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGrade 4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eGrade 5\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNausea\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChills\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHeadache\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVomiting\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSinus tachycardia\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBone pain\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePain in the extremity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRash\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePetechiae\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003edyspnea\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe number and grade of adverse events that were considered to have a possible or probable causal relationship with treatment using alloreactive CD56⁺ cells. Patients with adverse events associated with conditioning regimens were excluded.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Clinical outcomes\u003c/h2\u003e\u003cp\u003eFollowing the administration of the FLAG chemotherapy regimen and CD56\u0026thinsp;+\u0026thinsp;cell infusion, hematopoietic recovery was similar to what is typically observed after a standard chemotherapy cycle. The median time to absolute neutrophil count recovery (neutrophil count\u0026thinsp;\u0026gt;\u0026thinsp;0.5 \u0026times; 10⁶/\u0026micro;L for three consecutive days) was 23 days (range 17\u0026ndash;42), and the median time to platelet recovery (platelet count\u0026thinsp;\u0026gt;\u0026thinsp;20 \u0026times; 10⁶/\u0026micro;L for three consecutive days) was 21 days (range 18\u0026ndash;39).\u003c/p\u003e\u003cp\u003eAll patients underwent three planned infusions of CD56\u0026thinsp;+\u0026thinsp;cells. On day 28 following cell infusion, five patients responded to therapy, four patients achieved CR (4/11, 36.3%), and one patient achieved CR with incomplete hematologic recovery(1/11, 9%). Among them, one patient (P.3) relapsed after two months and succumbed to PD. Additionally, one patient (P.9) achieved negative MRD accompanied by a reduction in blasts from 15% before CD56\u0026thinsp;+\u0026thinsp;cell infusion to 1% after CD56\u0026thinsp;+\u0026thinsp;cell infusion. Among the other six patients, three (27.2%) reached SD with a slight reduction in blast percentage, and three (27.2%) experienced PD with an increase in blasts. All six non-remission patients underwent further chemotherapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFour patients who achieved CR were deemed eligible for HSCT and had suitable stem cell donors. Among them, two patients (P.5 and P.9) received two additional doses of CD56\u0026thinsp;+\u0026thinsp;cells as maintenance therapy before undergoing HSCT. These four patients (4/11, 36.3%) proceeded to allogeneic HSCT in sustained remission at days 57, 63, 128, and 92 post-CD56\u0026thinsp;+\u0026thinsp;cell therapy and remained alive with their disease in CR.\u003c/p\u003e\u003cp\u003eWith a median follow-up of 6.5 months (range: 2\u0026ndash;19), the one-year OS and event-free survival (EFS) rates for the entire cohort were both 36.4% (95% CI: 10.9\u0026ndash;69.2). Patients who achieved CR/CRi had a significantly greater EFS of 80.0% (95% CI: 28.4\u0026ndash;99.5) compared with 0% (95% CI: 0\u0026ndash;45.9) in non-responders (p\u0026thinsp;=\u0026thinsp;0.015). Furthermore, all patients who responded and underwent HSCT remained event-free at one year (100%, 95% CI: 39.8\u0026ndash;100), whereas non-responders had an EFS of 0% (p\u0026thinsp;=\u0026thinsp;0.005).\u003c/p\u003e\u003cp\u003eBased on these findings, our trial protocol, which involves CD56\u0026thinsp;+\u0026thinsp;cell infusion combined with FLAG regimen chemotherapy, was proposed as a successful bridge to HSCT in approximately 36.4% of patients by delivering an effective dose of CD56\u0026thinsp;+\u0026thinsp;cells.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eAlthough chemotherapy remains the standard first-line treatment for AML, approximately 10\u0026ndash;40% of newly diagnosed patients do not respond to induction therapy and fail to achieve CR, a condition referred to as primary refractory AML. Additionally, among those who initially respond to chemotherapy, nearly half experience disease relapse. Together, chemotherapy resistance and relapse represent the major causes of mortality in AML patients (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). A variety of salvage regimens, ranging from non-intensive to intensive, have been utilized in refractory/relapsed AML patients to bridge patients to the only potentially curative option, allogeneic HSCT. However, most of these approaches are not promising due to the lack of sufficient efficacy or high toxicity (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eImmunotherapy based on adoptive CD56\u0026thinsp;+\u0026thinsp;cells (including NK and NKT-like cells) has recently gained attention as a therapeutic strategy. The alloreactivity of NK cells due to donor and recipient KIR and HLA class I mismatch leads to GVL reactions, facilitating engraftment, and protecting against GVHD. Moreover, rapid NK cell recovery after HSCT is associated with improved outcomes, whereas impaired NK cell function is linked to disease progression (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the present study, we report the results of a phase I trial involving the infusion of KIR ligand\u0026ndash;mismatched CD56\u003csup\u003e+\u003c/sup\u003e NK/NKT-like cells in 11 adult patients with R/R non-M3 AML. Our findings, in line with previous studies, showed that administering CD56\u0026thinsp;+\u0026thinsp;cells was safe, with no infusion-related adverse events, including CRS, neurotoxicity, or GVHD (\u003cspan additionalcitationids=\"CR23 CR24 CR25\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Dose escalation was well tolerated, with a high dose of 5 \u0026times; 10⁶ cells/kg, which represents the maximum yield routinely achievable from single-donor leukapheresis. Our results indicated that five patients achieved CR/CRi and became eligible for allogenic HSCT, and four of them proceeded to subsequent allogenic HSCT. At the censoring date, four patients were alive and in CR following transplantation. These clinical results suggest that this type of cell therapy may convert refractory or relapsed AML patients into transplant candidates, ultimately leading to a possible cure.\u003c/p\u003e\u003cp\u003eNumerous clinical trials have investigated the adoptive transfer of NK cells following HSCT, either as a strategy to treat disease relapse or as a prophylactic (preemptive) approach to inhibit disease progression (\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In addition, clinical trials using allogeneic NK cells outside the transplantation setting to induce remission or as a consolidation therapy to extend CR have been conducted, and various manufacturing strategies and clinical protocols have been developed. Fehniger \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) reported a phase I dose-escalation study in which 12 high-risk AML patients received cyclophosphamide and fludarabine followed by haploidentical NK cell infusions (CD3-CD56\u0026thinsp;+\u0026thinsp;cells) primed with CTV-1 leukemia cell lysate in their first CR, showing no dose-limiting toxicities; notably, three patients achieved remarkably durable CR lasting 33\u0026ndash;48 months after therapy. Bj\u0026ouml;rklund \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) explored the safety and efficacy of IL-2-activated haploidentical NK cells in combination with lymphodepleting chemotherapy consisting of fludarabine, cyclophosphamide, and total lymphoid irradiation in 16 patients with refractory or relapsed AML/MDS who were ineligible for HSCT. In this trial, 37.5% of patients (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6) responded to NK-cell therapy, 31.25% achieved CR, and five patients subsequently underwent allogeneic HSCT. Ciurea \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) performed a phase I study in which 12 relapsed/refractory AML patients received FLAG chemotherapy plus six infusions of haploidentical NK cells expanded with engineered K562 feeder cells, achieving a CR rate of 58.3%, with a favorable safety profile, and five patients bridged to transplantation via the same donor. Conversely, a phase I study evaluating allogeneic expanded NK cell infusion on days 0 and +\u0026thinsp;7 following a conditioning regimen of fludarabine-endoxan in nine relapsed/refractory AML patients reported no CR achievement (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Based on the aforementioned studies, to the best of our knowledge, we are conducting the first clinical trial to evaluate the safety and efficacy of infusing CD56\u0026thinsp;+\u0026thinsp;cells, comprising a mixture of NK and NKT-like cells, with the specific goal of inducing remission and serving as a bridge to transplantation in adult patients with relapsed or refractory AML.\u003c/p\u003e\u003cp\u003ePeripheral blood-derived NK cells, which have been widely utilized in clinical trials, are typically obtained from leukapheresis products as the initial source. To enrich the NK cell fraction, T cells can be depleted via anti-CD3 microbeads; however, this approach still results in a mixed population of other cell subsets, including residual B cells and monocytes. To reduce B-cell contamination further, anti-CD19 beads are subsequently applied. By sequential depletion of T cells followed by CD56\u0026thinsp;+\u0026thinsp;cell enrichment, a highly purified NK cell population can be obtained, but this approach remains time-consuming and costly (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). An alternative and more cost-effective approach is the single-step selection of CD56\u0026thinsp;+\u0026thinsp;cells, which yields a final cellular product containing a mixed population of NK and NKT-like cells (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBoth NK (CD3⁻CD56⁺) and NKT-like (CD3⁺CD56⁺) cells belong to the innate lymphocyte population. NKT-like cells constitute only a small fraction (0.2\u0026ndash;8%) of total peripheral lymphocytes and are believed to play essential roles in various immune-related diseases, particularly cancer (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Previous studies have shown a statistically significant correlation between the number of peripheral blood CD3⁺CD56⁺ NKT-like cells and a favorable prognosis in various types of cancer, including leukemia (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Key cytotoxic molecules, such as perforin and granzyme levels, are significantly lower in patients with acute leukemia than in healthy individuals, indicating a CD3\u0026thinsp;+\u0026thinsp;CD56\u0026thinsp;+\u0026thinsp;cells functional impairment that may compromise their ability to eliminate leukemic clones (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn preclinical models, CD8-expressing CD3\u0026thinsp;+\u0026thinsp;CD56\u0026thinsp;+\u0026thinsp;NKT cells have been shown to maintain GVL activity without exacerbating GVHD (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Recent trial studies have provided evidence supporting the beneficial immunological effects of NKT-like cells in the setting of allogeneic allo-HSCT. Jaiswal \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) demonstrated that the adoptive transfer of CD56-enriched donor lymphocytes, following posttransplant cyclophosphamide-based haploidentical HSCT, promotes robust reconstitution of NK cells and reduces the incidence of aGVHD. Kulkarni \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) evaluated the therapeutic potential of a single dose of haploidentical CD56⁺ cell infusions (median total dose: 41.6 \u0026times; 10⁶/kg, comprising 26.47 \u0026times; 10⁶ CD3⁻CD56⁺ cells/kg and 13.36 \u0026times; 10⁶ CD3⁺CD56⁺ cells/kg) as an adjunct to sequential transplantation in 14 patients with relapsed/refractory AML, aiming to selectively target and eradicate pretransplant MRD and thereby improve post-HSCT outcomes. In terms of efficacy, although definitive efficacy could not be demonstrated due to the small sample size and high nonrelapse mortality, the mean blast percentage decreased from 15.87% to 11.92% following cell infusion, and patients with greater MRD reduction appeared to achieve better disease control post-HSCT. These findings suggest that the transfer of NKT-like cells along with NK cells may represent a promising therapeutic strategy to enhance antileukemic immunity and improve the outcomes in AML patients.\u003c/p\u003e\u003cp\u003eInterleukin-15 (IL-15) plays a crucial role in the differentiation, expansion, and survival of NK cells (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Although Miller \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) demonstrated that high-dose lymphodepleting regimens markedly increase endogenous IL-15 production, resulting in promoting the \u003cem\u003ein vivo\u003c/em\u003e proliferation of NK cells. More recent data from Dr. Rezvani's group indicated that serum IL-15 levels remain largely unchanged following lymphodepleting or NK cell infusion (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Notably, even at the lowest doses of infused NK cells, in vivo persistence and expansion of donor-derived NK cells were observed during the first week after the final infusion (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Moreover, expansion of regulatory T cells following lymphodepleting therapy in the absence of IL-2 administration has also been reported, which may limit the engraftment and in vivo efficacy of donor-derived NK cells (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). One limitation of the current study is the absence of longitudinal tracking of donor CD56\u003csup\u003e+\u003c/sup\u003e cell engraftment kinetics, cytokine profiles, and regulatory T-cell changes following chemotherapy. Thus, future studies are recommended to identify better factors influencing in vivo CD56\u0026thinsp;+\u0026thinsp;cell expansion and functional activity.\u003c/p\u003e\u003cp\u003eFinally, this study was not designed to characterize the features of CD56\u0026thinsp;+\u0026thinsp;cell products before infusion. This limitation will be addressed in a planned phase 2 clinical trial through a comprehensive analysis of activating and inhibitory receptor expression on CD56\u0026thinsp;+\u0026thinsp;cells.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings demonstrated that multiple infusions of KIR ligand\u0026ndash;mismatched CD56\u0026thinsp;+\u0026thinsp;cells, intended to reduce disease burden and prepare patients with relapsed or refractory AML for subsequent allogeneic HSCT, were feasible and safe. Although tumor response was not the primary objective of this study, 4 out of 11 patients achieved remission and subsequently underwent transplantation, and all of them were alive in remission at the time of the last follow-up. However, despite these encouraging preliminary results, the findings should be interpreted with caution due to the limited sample size, which restricts the ability to draw definitive conclusions regarding clinical efficacy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank our clinical collaborators for their expert care and unwavering dedication throughout this study. We are especially grateful to the patient volunteers and donors, whose trust and generous participation made this clinical trial possible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eE.R.: Conceptualization, Methodology, Data Analysis and, validation. A.SG. and A.I.: Investigation. A.H. and A.G.: Supervision and Validation A.I., M.S-A., and M.BD.: CD56⁺ cell collection and processing, Flow Cytometry, Molecular assays. M.BD. and M.SA.: Data Analysis. S.P., A.S., and H.RS.: Project Administration. M.BD., S.Y., and A.SG.: Writing \u0026ndash; Review \u0026amp; Editing. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"RTL\" style=\"text-align: left;\"\u003eThe authors received no financial support for the research, authorship, and publication of this article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eavailability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data generated or analyzed during this study have been included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients and donors provided written informed consent in accordance with the Declaration of Helsinki.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019;12(1):100.\u003c/li\u003e\n\u003cli\u003ePandolfi A, Barreyro L, Steidl U. Concise review: preleukemic stem cells: molecular biology and clinical implications of the precursors to leukemia stem cells. Stem Cells Transl Med. 2013;2(2):143-50.\u003c/li\u003e\n\u003cli\u003eForsberg M, Konopleva M. AML treatment: conventional chemotherapy and emerging novel agents. Trends Pharmacol Sci. 2024;45(5):430-48.\u003c/li\u003e\n\u003cli\u003eSasaki K, Ravandi F, Kadia TM, DiNardo CD, Short NJ, Borthakur G, et al. De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer. 2021;127(12):2049-61.\u003c/li\u003e\n\u003cli\u003eBall B, Stein EM. Which are the most promising targets for minimal residual disease-directed therapy in acute myeloid leukemia prior to allogeneic stem cell transplant? Haematologica. 2019;104(8):1521-31.\u003c/li\u003e\n\u003cli\u003eLichtenegger FS, Krupka C, Haubner S, Köhnke T, Subklewe M. Recent developments in immunotherapy of acute myeloid leukemia. J Hematol Oncol. 2017;10(1):142.\u003c/li\u003e\n\u003cli\u003eSpits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13(2):145-9.\u003c/li\u003e\n\u003cli\u003eTsirogianni M, Grigoriou E, Kapsimalli V, Dagla K, Stamouli M, Gkirkas K, et al. Natural killer cell cytotoxicity is a predictor of outcome for patients with high risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia treated with azacytidine. Leuk Lymphoma. 2019;60(10):2457-63.\u003c/li\u003e\n\u003cli\u003eLowdell MW, Craston R, Samuel D, Wood ME, O'Neill E, Saha V, et al. Evidence that continued remission in patients treated for acute leukaemia is dependent upon autologous natural killer cells. Br J Haematol. 2002;117(4):821-7.\u003c/li\u003e\n\u003cli\u003eTorelli GF, Guarini A, Palmieri G, Breccia M, Vitale A, Santoni A, et al. Expansion of cytotoxic effectors with lytic activity against autologous blasts from acute myeloid leukaemia patients in complete haematological remission. Br J Haematol. 2002;116(2):299-307.\u003c/li\u003e\n\u003cli\u003eBakhtiyaridovvombaygi M, Yazdanparast S, Mikanik F, Izadpanah A, Parkhideh S, Shahbaz Ghasabeh A, et al. Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. Biomed Pharmacother. 2023;168:115718.\u003c/li\u003e\n\u003cli\u003eRahmani S, Yazdanpanah N, Rezaei N. Natural killer cells and acute myeloid leukemia: promises and challenges. Cancer Immunol Immunother. 2022;71(12):2849-67.\u003c/li\u003e\n\u003cli\u003eD'Silva SZ, Singh M, Pinto AS. NK cell defects: implication in acute myeloid leukemia. Front Immunol. 2023;14:1112059.\u003c/li\u003e\n\u003cli\u003eMiller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051-7.\u003c/li\u003e\n\u003cli\u003eBjörklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M, et al. Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML. Clin Cancer Res. 2018;24(8):1834-44.\u003c/li\u003e\n\u003cli\u003eDöhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-77.\u003c/li\u003e\n\u003cli\u003eCheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642-9.\u003c/li\u003e\n\u003cli\u003eLi K, Du Y, Cai Y, Liu W, Lv Y, Huang B, et al. Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed/refractory acute myeloid leukemia. Leukemia. 2023;37(2):308-25.\u003c/li\u003e\n\u003cli\u003eThol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood. 2015;126(3):319-27.\u003c/li\u003e\n\u003cli\u003eWattad M, Weber D, Döhner K, Krauter J, Gaidzik VI, Paschka P, et al. Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia. 2017;31(6):1306-13.\u003c/li\u003e\n\u003cli\u003eXu J, Niu T. Natural killer cell-based immunotherapy for acute myeloid leukemia. J Hematol Oncol. 2020;13(1):167.\u003c/li\u003e\n\u003cli\u003eCiurea SO, Kongtim P, Srour S, Chen J, Soebbing D, Shpall E, et al. Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML. Am J Hematol. 2024;99(5):890-9.\u003c/li\u003e\n\u003cli\u003eFehniger TA, Miller JS, Stuart RK, Cooley S, Salhotra A, Curtsinger J, et al. A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2018;24(8):1581-9.\u003c/li\u003e\n\u003cli\u003eAhmadvand M, Barough MS, Barkhordar M, Faridfar A, Ghaderi A, Jalaeikhoo H, et al. Phase I non-randomized clinical trial of allogeneic natural killer cells infusion in acute myeloid leukemia patients. BMC Cancer. 2023;23(1):1090.\u003c/li\u003e\n\u003cli\u003eKottaridis PD, North J, Tsirogianni M, Marden C, Samuel ER, Jide-Banwo S, et al. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial. PLoS One. 2015;10(6):e0123416.\u003c/li\u003e\n\u003cli\u003eOtegbeye F, Cooper B, Caimi P, Zamborsky K, Reese-Koc J, Hillian A, et al. A Phase I Study to Determine the Maximum Tolerated Dose of ex Vivo Expanded Natural Killer Cells Derived from Unrelated, HLA-Disparate Adult Donors. Transplant Cell Ther. 2022;28(5):250.e1-.e8.\u003c/li\u003e\n\u003cli\u003eMushtaq MU, Shahzad M, Shah AY, Chaudhary SG, Zafar MU, Anwar I, et al. Impact of natural killer cells on outcomes after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis. Front Immunol. 2022;13:1005031.\u003c/li\u003e\n\u003cli\u003eBednarski JJ, Zimmerman C, Berrien-Elliott MM, Foltz JA, Becker-Hapak M, Neal CC, et al. Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. Blood. 2022;139(11):1670-83.\u003c/li\u003e\n\u003cli\u003eChoi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, et al. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant. 2014;20(5):696-704.\u003c/li\u003e\n\u003cli\u003eCiurea SO, Kongtim P, Soebbing D, Trikha P, Behbehani G, Rondon G, et al. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022;36(1):155-64.\u003c/li\u003e\n\u003cli\u003eShimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020;19(3):200-18.\u003c/li\u003e\n\u003cli\u003eJaiswal SR, Zaman S, Nedunchezhian M, Chakrabarti A, Bhakuni P, Ahmed M, et al. CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: A pilot study. Cytotherapy. 2017;19(4):531-42.\u003c/li\u003e\n\u003cli\u003eKulkarni U, Arunachalam AK, Palani HK, Nair RR, Balasundaram N, Venkatraman A, et al. Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia. Cell Transplant. 2023;32:9636897231198178.\u003c/li\u003e\n\u003cli\u003eMin XY, Liu CF, Cao B, Zhang T, Yang X, Ma N, et al. Human CD3(+)CD56(+)NKT-like cells express a range of complement receptors and C3 activation has negative effects on these cell activity and effector function. Hum Immunol. 2021;82(9):625-33.\u003c/li\u003e\n\u003cli\u003eGuo W, Xing C, Dong A, Lin X, Lin Y, Zhu B, et al. Numbers and cytotoxicities of CD3+CD56+ T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia. Cancer Biol Ther. 2013;14(10):916-21.\u003c/li\u003e\n\u003cli\u003eBaker J, Verneris MR, Ito M, Shizuru JA, Negrin RS. Expansion of cytolytic CD8(+) natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon gamma production. Blood. 2001;97(10):2923-31.\u003c/li\u003e\n\u003cli\u003eHuntington ND, Puthalakath H, Gunn P, Naik E, Michalak EM, Smyth MJ, et al. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol. 2007;8(8):856-63.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cancer-immunology-immunotherapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ciim","sideBox":"Learn more about [Cancer Immunology, Immunotherapy](http://link.springer.com/journal/262)","snPcode":"262","submissionUrl":"https://submission.nature.com/new-submission/262/3","title":"Cancer Immunology, Immunotherapy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Acute myeloid leukemia, Relapsed/refractory, Natural killer cells, CD56+ cells, Hematopoietic stem cell transplantation","lastPublishedDoi":"10.21203/rs.3.rs-7593855/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7593855/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and purpose.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcute myeloid leukemia (AML) is an aggressive disease with suboptimal overall survival, especially in relapsed/refractory patients. The primary goal of salvage therapy in this patient is to achieve optimal disease control, thereby allowing the transition to hematopoietic stem cell transplantation (HSCT), which remains the only curative option for a subset of these patients. Allogeneic KIR ligand–mismatched CD56\u003csup\u003e+\u003c/sup\u003e NK/NKT-like cells have demonstrated anti-leukemic activity and represent a promising platform for the development of novel cellular therapies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRelapsed/refractory non-M3 AML patients who were not HSCT candidates were included in this phase I clinical trial. Patients received the FLAG conditioning regimen followed by three escalating doses (1×10⁶, 3×10⁶, 5×10⁶ cells/kg) of CD56\u003csup\u003e+\u003c/sup\u003e NK/NKT-like cells at 5-day intervals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 11 patients with a median age of 41.5 years were enrolled in the study. On average, they received three lines of prior chemotherapy and showed 18% blasts in their bone marrow. The infusion of CD56⁺ NK/NKT-like cells was safe, with no serious toxicity or graft-versus-host disease (GVHD) observed in any patient. Following this treatment protocol, five patients (45.4%) achieved complete remission (CR), with or without hematologic count recovery. Four of these patients (36.3%) underwent successful HSCT and remained event-free to the end of the follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, these trials indicated that the FLAG regimen chemotherapy combined with allogeneic KIR ligand–mismatched CD56\u003csup\u003e+\u003c/sup\u003e NK/NKT-like cell infusion is safe and may serve as an effective bridge to HSCT in 36.3% of patients with refractory/relapsed non-M3 AML.\u003c/p\u003e","manuscriptTitle":"Allogeneic Cd56+ Cell Infusion As A Bridge To Hematopoietic Stem Cell Transplantation In Relapsed/Refractory Acute Myeloid Leukemia: A Phase I Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-25 01:32:58","doi":"10.21203/rs.3.rs-7593855/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-20T00:58:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-19T17:57:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-05T20:37:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140075893297862190435325130665870917866","date":"2025-10-02T14:10:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-02T12:52:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"307288377677414648786705873768709843237","date":"2025-09-22T11:43:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286736706152944982731122127368190819792","date":"2025-09-20T08:21:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-16T09:17:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-15T09:20:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-15T09:20:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cancer Immunology, Immunotherapy","date":"2025-09-11T16:29:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cancer-immunology-immunotherapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ciim","sideBox":"Learn more about [Cancer Immunology, Immunotherapy](http://link.springer.com/journal/262)","snPcode":"262","submissionUrl":"https://submission.nature.com/new-submission/262/3","title":"Cancer Immunology, Immunotherapy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1b1602ff-6580-4006-900e-b6b44d28778e","owner":[],"postedDate":"September 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T16:03:20+00:00","versionOfRecord":{"articleIdentity":"rs-7593855","link":"https://doi.org/10.1007/s00262-025-04285-9","journal":{"identity":"cancer-immunology-immunotherapy","isVorOnly":false,"title":"Cancer Immunology, Immunotherapy"},"publishedOn":"2026-03-31 16:00:07","publishedOnDateReadable":"March 31st, 2026"},"versionCreatedAt":"2025-09-25 01:32:58","video":"","vorDoi":"10.1007/s00262-025-04285-9","vorDoiUrl":"https://doi.org/10.1007/s00262-025-04285-9","workflowStages":[]},"version":"v1","identity":"rs-7593855","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7593855","identity":"rs-7593855","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}