Reduced Intensity T-Replete Allogeneic Stem Cell Transplantation Provides Long-Term Survival in Relapsed Angioimmunoblastic T-Cell Lymphoma Post-Autologous Transplant in patients over the age of 50

Reduced Intensity T-Replete Allogeneic Stem Cell Transplantation Provides Long-Term Survival in Relapsed Angioimmunoblastic T-Cell Lymphoma Post-Autologous Transplant in patients over the age of 50 | 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 Article Reduced Intensity T-Replete Allogeneic Stem Cell Transplantation Provides Long-Term Survival in Relapsed Angioimmunoblastic T-Cell Lymphoma Post-Autologous Transplant in patients over the age of 50 Emmanouil Nikolousis, Ioannis Arvantis, Cristina Maschio, Julieta Osorio Zuluaga, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8761905/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Relapsed angioimmunoblastic T-cell lymphoma (AITL) following autologous transplantation carries poor prognosis. Reduced-intensity T-replete allogeneic transplant may provide durable disease control via immune-mediated graft effects. Methods We retrospectively analyzed 21 patients over the age of 50 with relapsed AITL who underwent reduced-intensity T-replete allo-HCT across three transplant centers between 2013 and 2022. Following salvage treatment, all patients experienced chemo sensitive disease and proceeded to transplantation. Responses were PET-based, and survival outcomes were assessed. Results All patients achieved hematologic engraftment, with 13 in complete metabolic remission and 8 in partial remission at the time of transplant. At a median follow-up of 7.55 years, OS was 100%, 81%, and 71% at 1, 2, and 5 years, respectively, with PFS of 95%, 95%, and 84%. Seven deaths occurred, four due to disease progression and three related to transplantation. Acute and chronic GvHD were observed in 30% and 22% of patients respectively. Five patients received donor lymphocyte infusion, showing a trend toward improved survival. Conclusion Reduced-intensity T-replete allo-HCT is a feasible and potentially curative therapeutic option for patients over 50 with chemo sensitive relapsed AITL after autologous transplantation. Early disease control and long-term remission suggest a clinically meaningful graft-versus-lymphoma (GVL) effect in appropriately selected individuals. Health sciences/Diseases/Haematological diseases/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/T-cell lymphoma Health sciences/Diseases/Cancer/Cancer therapy Figures Figure 1 Figure 2 Figure 3 Introduction Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of primary nodal peripheral T-cell lymphoma (PTCL), accounting for approximately 1–2% of all non-Hodgkin lymphomas (NHLs) [ 1 ]. The majority of patients present with advanced disease, frequently manifesting as generalized lymphadenopathy, hepatosplenomegaly, and hypergammaglobulinemia [ 2 ]. Even when AITL is treated with intensive induction regimens, the prognosis can be poor. Standard first-line therapy typically consists of anthracycline-based chemotherapy, with or without etoposide, depending on the patient’s age, and, for those who are CD30 positive, brentuximab combined with chemotherapy [ 1 , 3 ]. Patients who achieve complete remission (CR) and have a favorable performance status often proceed with autologous hematopoietic cell transplantation (auto-HCT) consolidation to achieve long term remission. Despite this approach, outcomes remain unsatisfactory due to significant relapse rates[ 4 ]. Allogeneic hematopoietic cell transplantation (allo-HCT) has emerged as a potentially curative strategy for patients with relapsed AITL following auto-HCT [ 5 – 8 ], possibly owing to the graft-versus-lymphoma (GVL) effect mediated by donor immune cells [ 9 , 10 ]. AITL originates from follicular helper T-cells and is characterized by immune dysregulation and EBV-induced B-cell proliferation, factors that may influence the response to immune-mediated GVL effects [ 11 ]. Allogeneic grafts can be categorized as T-cell-replete or T-cell-depleted depending on whether donor T-cells remain in the graft or are eliminated. T-depleted techniques minimize the risk of graft-versus-host disease (GvHD), but they may compromise disease control. On the other side, T-replete transplantation preserves donor T-cells, which can mediate a positive GVL effect but at the expense of increased GvHD risk [ 9 , 12 ]. Donor lymphocyte infusion (DLI), which can employ donor immune cells to improve disease control in certain hematologic malignancies, including AITL, may also be beneficial for treating relapse following allogeneic stem cell transplantation [ 8 ]. Reduced-intensity conditioning (RIC) regimens, being less toxic and intense, allo-HCT to be offered to older or frail patients while preserving graft immunologic function [ 13 ]. Nevertheless, few studies have specifically evaluated reduced-intensity, T-replete allo-HCT in this setting, and the evidence for an early GVL effect remains limited. In an effort to channel a potential graft-versus-lymphoma effect following previous unsuccessful auto-HCT, we examined the therapeutic role of reduced-intensity, T-replete allogeneic transplantation in patients over 50 with relapsed AITL who achieved a chemo sensitive response to salvage therapy. Methodology Study Design and Patient Population This was a retrospective, multicenter cohort study designed to evaluate the efficacy of reduced-intensity, T-replete allogeneic hematopoietic cell transplantation in patients with relapsed angioimmunoblastic T-cell lymphoma. The study included three bone marrow transplant (BMT) centers and comprised 21 patients who underwent allo-HCT following prior autologous HCT between 2013 and 2019. All patients were aged 50 years and above at the time of diagnosis and had experienced relapse after auto-HCT. Patients received salvage chemotherapy with GDP (gemcitabine, dexamethasone, cisplatin), ICE (ifosfamide, carboplatin, etoposide), or mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Those achieving complete response (CR) or partial response (PR) to salvage therapy were considered chemosensitive and were eligible for transplantation [ 14 ]. Response Evaluation and Definitions Pre-transplant response to salvage chemotherapy was assessed using 18 F-FDG PET/CT. Patients who demonstrated a complete or partial metabolic response by PET criteria [ 15 ] proceeded to reduced-intensity T-replete allo-HCT. The following endpoints were established according to the Revised Response Criteria for Malignant Lymphoma [ 14 ]. Overall survival (OS) was defined as the time between stem cell transplantation and death from any cause. Progression-free survival (PFS) was defined as the time between stem cell transplantation and lymphoma relapse, progression, or death from any cause, whichever occurred first. Non-relapse mortality (NRM) was defined as death from any cause without prior disease progression. Acute (grades I-IV) and chronic (limited or extensive) graft-versus-host disease (GvHD) were graded according to international consensus standards [ 16 , 17 ]. Transplant Procedure Among the 21 patients included in this study, 15 were males, and 6 were females, with a median age of 58.3 years (50–73). Eight patients were in partial remission, and thirteen were in complete remission at the time of transplantation, based on PET/CT criteria. Five patients received an HLA-matched sibling allogeneic transplant, and sixteen received a fully matched volunteer unrelated donor transplant. Eligible donors were matched at the allele level for HLA-A, -B, -C, -DQ, and -DRB1. The conditioning regimen was classified as reduced-intensity according to the established EBMT criteria [ 18 ] and consisted of fludarabine, cyclophosphamide, and a single fraction 2Gy total body irradiation (TBI). In total, 5 patients received donor lymphocyte infusion (DLI) at a dose of 1 x 10^6 cells/kg for post-transplant relapse. All patients received peripheral blood stem cell transplants. The median infused stem cell dose was 4.7X 10 6 CD34/kg (4.0-6.2 x 10 6 CD34/kg). Neutrophil engraftment was defined as an absolute neutrophil count (ANC) greater than 0.5 X 10 9 /L for two consecutive days following allo-HCT, and platelet engraftment as a platelet count greater than 20 X 10 9 /L for two consecutive days, unsupported. Cyclosporine and methotrexate were used for graft-versus-host disease (GvHD) prophylaxis. Statistical Analysis A descriptive analysis was initially performed to summarize the demographic and clinical characteristics of the study population. Patients were censored at the date of last contact for survival analyses. Median age and ranges were reported, along with transplantation- and treatment-related characteristics. Survival outcomes were assessed using the Kaplan–Meier method. Overall survival (OS) was estimated from the date of transplantation until the date of death due to any cause or the last follow-up. Progression-free survival (PFS) was defined as the time between transplantation and disease progression, relapse, or death, whichever came first. Survival probabilities at 1, 2, and 5 years were estimated using 95% confidence intervals. Comparisons of survival between patient subgroups (e.g., patients receiving donor lymphocyte infusion versus those who did not) were conducted using the log-rank test. Mortality analysis was further performed to classify deaths into disease progression and HSCT-related mortality. Engraftment kinetics and graft-versus-host disease (GvHD) incidence were also reported descriptively. All statistical analyses were performed using R version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria) within the RStudio environment. A two-sided significance level of α = 0.05 was applied throughout. Ethical Issues The study was conducted in accordance with the Declaration of Helsinki and approved by the institutional review boards of all participating BMT centers. Informed consent for data use was obtained according to institutional policy. All patient data were anonymized prior to analysis to ensure confidentiality. Results The dataset included 21 patients with relapsed AITL who received allogeneic stem cell transplantation following a previous autologous transplant. Table 1 summarizes the demographic and clinical characteristics of patients. The median age at diagnosis was 61 years (40–73), with a male predominance (n = 15). The median follow-up after allogeneic transplantation was 7.55 years (0.3–10.7). Cytogenetic analysis was normal in most patients (n = 15), while isolated abnormalities were less common and included 5q gain (n = 3), 13q changes (n = 2), and gain of chromosome 21 (n = 1). The median infused stem cell dose was 5x10 6 (3.9-6.2x10 6 ). Patients mostly received grafts from unrelated donors (n = 16), while 5 had sibling donors. Donor–recipient CMV serostatus was concordantly positive in 10 cases and negative in 5, with 6 pairs showing discordance (either donor/recipient positive). In total, 14 out of 21 patients were CMV seropositive. Donor lymphocyte infusion (DLI) was administered in 5 patients. All patients achieved hematologic engraftment, both for neutrophils and platelets. Median neutrophil engraftment occurred on day + 17 (D + 14 - D + 25) and median platelet engraftment occurred on day + 20 (D + 18 - D + 26). Ten patients experienced acute GvHD (grades I–III), while 11 had no acute GvHD. Chronic GvHD occurred in 4 patients (all limited). In total, 13 patients (62%) had a complete metabolic response, and 8 patients (38%) had a partial metabolic response to salvage chemotherapy prior to allogeneic transplant. There were 7 deaths, 4 of which were due to disease progression, and 3 were HSCT-related. Table 1 Patients’ characteristics Variable N = 21 Age at diagnosis Follow-up (in years) 61 (40–73) 7.55 (0.3–10.7) Sex Male 15 Female 6 Cytogenetics Normal 15 5 gain 3 13q 2 Gain 21 1 Stem cell dose 5x10 6 (3.9–6.2 x 10 6 ) Donor type Sibling 5 Unrelated 16 Donor/Recipient CMV status Both negative 5 Both positive 10 Either donor/recipient + 6 CMV status (patient) Positive 14 Negative 7 CMV status (donor) Positive 10 Negative 11 Donor DLI Yes 5 No 16 Engraftment Neutrophil Engraftment Platelet Engraftment D + 17 (D + 14 - D + 25) D + 20 (D + 18 - D + 26) Acute GvHD Grade 0 11 Grade I 3 Grade II 4 Grade III 3 Chronic GvHD None 17 Limited 4 Metabolic Response Complete Partial Mortality 13 8 7 Cause of death Progression 4 HSCT related 3 Relapse and Non-Relapse Mortality At the latest follow-up, 7 patients (33%) had passed away and 14 patients (67%) were still alive. Analysis of the cohort's mortality causes showed that, of the 7 patients with a documented cause of death, 4 (57.1%) died due to disease progression, and 3 (42.9%) succumbed as a result of hematopoietic stem cell transplantation (HSCT), indicating non-relapsed mortality. The median time to relapse among relapsed cases was 22 months (8–92 months) following transplantation. These findings highlight the substantial impact that transplantation-related complications and disease progression have on patient survival. Overall Survival The Kaplan-Meier overall survival analysis (Fig. 1 ) showed OS rates of 100% at 1 year, 81% at 2 years, and 71% at 5 years. The survival probability remains high for the first year, followed by a gradual decline over the 5-year follow-up period. Progression-Free Survival Figure 2 depicts a Kaplan-Meier analysis of PFS, which revealed a probability of 95% at 1 year, 95% at 2 years, and 84% at 5 years. The survival curve remains steady for the first two years but declines after five years, indicating disease progression in a subset of patients. Acute and Chronic GvHD At three months post transplant, the cumulative incidence of grade II-IV acute GvHD was 38% (95% CI 32–45), and grade III-IV acute GvHD was 15% (95% CI 8–21). Acute GvHD predominantly affects the skin, gastrointestinal tract, and liver. The 1-year cumulative incidence of chronic GvHD was 46% (95% CI 39–54), while the 1-year cumulative incidence of extensive chronic GvHD was 35% (95% CI 29–44). DLI & Survival Kaplan-Meier survival analysis comparing patients who received DLI versus those who did not (Fig. 3 ) showed a trend toward improved survival in the DLI group. Although this difference was not statistically significant (log-rank test, p = 0.5544), DLI appeared to contribute to durable immune-mediated disease control. Among DLI recipients, 4 of them (80%) remained alive at the end of the follow-up, while one (20%) experienced HSCT-related mortality. Discussion In this retrospective multicenter cohort study, reduced intensity T-replete allogeneic stem cell transplantation showed promising long-term survival in patients with relapsed AITL following prior autologous transplantation, a population that has traditionally been linked to few therapeutic options and poor outcomes. Of the 21 individuals in this sample, 8 achieved a partial metabolic response while 13 achieved a complete response. All patients achieved hematologic engraftment, and both OS (100% at 1 year and 71% at 5 years) and PFS (95% at 1–2 years and 84% at 5 years) remained high during the early post-transplant period, suggesting that elderly patients with chemosensitive relapse may benefit from the potentially curative approach of T-replete grafts. At the end of the study, 7 patients had died; disease progression accounted for 57.1% of these deaths, while HSCT-related causes (non-relapsed mortality) accounted for the remaining instances. Several factors may have contributed to the favorable outcomes observed. Firstly, all patients proceeded to transplantation with chemosensitive disease, which has been consistently associated with an improved post-transplant outcome in T-cell lymphomas, including AITL. Achieving a complete or partial remission prior to allo-HCT may have decreased disease burden, allowing donor immune reconstitution in the context of minimal residual lymphoma. Moreover, the use of a T-replete graft may have preserved donor T-cell function, supporting a stronger immunologic GvL effect. The early disease control, together with sustained remission observed in a significant portion of patients, supports the hypothesis that donor immune activity plays a critical role in long term lymphoma eradication. The universal engraftment and prompt neutrophil and platelet recovery further suggest the viability of allo-HCT in older transplant candidates over the age of 50. When compared to previous research, the results of our study appear promising. Epperla et al. achieved in their research a 4-year OS of 56% and PFS of 47–49% in relapsed AITL following allo-HCT, while Kyriakou et al. demonstrated durable remission although with more heterogeneous conditioning regimens. The improved survival rates observed in our cohort could be related to the combination of chemosensitive disease at transplantation and a uniform reduced-intensity T-replete transplant strategy. This highlights again the need of preserving donor T-cells for the development of an early and clinically relevant GvL response. In general, our findings indicate that for those patients with relapsed AITL who respond to salvage therapy, reduced-intensity T-replete allo-HCT may provide a viable option to long-term remission even if autologous transplant fails. Despite the sample size being limited, the increased survival observed in patients receiving DLI supports the notion that immune-mediated disease control may play an important role in this context. Although these findings are promising, GvHD still remained a transplant-related risk, with both acute and chronic GvHD observed in the study. The occurrence of GvHD reflects the inherent balance between desirable GvL activity and unwanted immune toxicity. Nonetheless, non-relapse mortality in older allo-HCT recipients remained limited relative to historical expectations, indicating that reduced-intensity conditioning may decrease toxicity while preserving immunologic benefit. The limitations of this study should be taken into consideration. Our findings have limited generalizability due to the intrinsic retrospective study design and the small sample size used in this research. Furthermore, due to a lack of molecular or genomic patient data, biological predictors of allo-HCT response cannot be established. This study only included chemosensitive patients, which could introduce selection bias toward favorable biology or treatment response. Future prospective multicenter studies should be conducted to confirm these findings, investigate biomarkers of transplant response, and optimize approaches that improve GvL activity while minimizing GvHD-related morbidity. Conclusion AITL has an uncertain prognosis when treated with conventional therapies, hence novel approaches are needed. This research comprised patients over the age of 50 who have relapsed AITL after autologous transplantation and for whom reduced-intensity T-replete allogeneic stem cell transplantation yields promising OS and PFS outcomes. Hematologic engraftment was achieved in all patients, suggesting that this approach is feasible even in elderly populations. This study demonstrates that the T-replete approach may offer long-term survival and induce an early GVL effect to the patients. Moreover, reduced-intensity conditioning can balance toxicity while preserving the donor immune function. Therefore, donor-derived immune activity is crucial to maintaining remission as seen by the favorable results achieved in patients receiving DLI. Due to the disease's rarity and the limited data given, new and larger research studies, possibly with integrated biologic profiling, are required to confirm our findings and identify effective strategies that preserve GVL effect while diminishing GvHD. References d’Amore F, Gaulard P, Trümper L, Corradini P, Kim WS., Specht L, et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [Internet]. 2015;26:v108–15. Available from: https://www.annalsofoncology.org/article/S0923-7534( 19)47172-X/pdf Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, et al. Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project. Journal of Clinical Oncology. 2013;31(2):240–6. Mourad N, Mounier N, Brière J, Raffoux E, Delmer A, Feller AC, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. BLOOD. 2008;111(9):4463–70. Charalampia Kyriakou, Canals C, Goldstone A, Caballero D, Metzner B, Kobbe G, et al. High-Dose Therapy and Autologous Stem-Cell Transplantation in Angioimmunoblastic Lymphoma: Complete Remission at Transplantation Is the Major Determinant of Outcome—Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of Clinical Oncology. 2007;26(2):218–24. Epperla N, Ahn KW, Litovich C, Ahmed S, Battiwalla M, Cohen JB, et al. Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis. Journal of Hematology & Oncology. 2019;12(1). Charalampia Kyriakou, Canals C, Finke J, Kobbe G, Jean-Luc Harousseau, Kolb H, et al. Allogeneic Stem Cell Transplantation Is Able to Induce Long-Term Remissions in Angioimmunoblastic T-Cell Lymphoma: A Retrospective Study From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of Clinical Oncology. 2009;27(24):3951–8. Delioukina M, Zain J, Palmer JM, Tsai N, Thomas S, Forman S. Reduced-intensity allogeneic hematopoietic cell transplantation using fludarabine–melphalan conditioning for treatment of mature T-cell lymphomas. Bone Marrow Transplantation. 2011;47(1):65–72. Mamez AC, Dupont A, Blaise D, Chevallier P, Forcade E, Ceballos P, et al. Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Journal of Hematology & Oncology. 2020;13(1). Hamadani M, Awan FT, Elder P, Lin TS, Peirluigi Porcu, Blum KA, et al. Allogeneic Hematopoietic Stem Cell Transplantation for Peripheral T Cell Lymphomas; Evidence of Graft-Versus-T Cell Lymphoma Effect. Biology of Blood and Marrow Transplantation. 2008;14(4):480–3. Corradini P, Dodero A, Zallio F, Caracciolo D, Casini M, Bregni M, et al. Graft-Versus-Lymphoma Effect in Relapsed Peripheral T-Cell Non-Hodgkin’s Lymphomas After Reduced-Intensity Conditioning Followed by Allogeneic Transplantation of Hematopoietic Cells. Journal of Clinical Oncology. 2004;22(11):2172–6. Feng Y, Ma Y, Li T, Liu M, Hong Z, Yin Q, et al. Angioimmunoblastic T-cell lymphoma: a concise overview encompassing the pathogenetic, pathological, clinical, therapeutical characteristics, and recent advances. Clinical and Experimental Medicine. 2025;25(1). Ciurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, et al. Improved Early Outcomes Using a T Cell Replete Graft Compared with T Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation. 2012;18(12):1835–44. Rodriguez R, Auayporn Nademanee, Ruel N, Smith E, Krishnan A, Popplewell L, et al. Comparison of Reduced-Intensity and Conventional Myeloablative Regimens for Allogeneic Transplantation in Non-Hodgkin’s Lymphoma. Biology of Blood and Marrow Transplantation. 2006;12(12):1326–34. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised Response Criteria for Malignant Lymphoma. Journal of Clinical Oncology [Internet]. 2007;25(5):579–86. Available from: https://imaging.cancer.gov/clinical_trials/docs/Cheson%20(IWG)%20Criteria%20JCO%202007.pdf Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. Journal of Clinical Oncology. 2014;32(27):3059–67. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplantation [Internet]. 1995;15(6):825–8. Available from: https://pubmed.ncbi.nlm.nih.gov/7581076/ Lee SJ. Classification systems for chronic graft-versus-host disease. Blood [Internet]. 2017;129(1):30–7. Available from: https://ashpublications.org/blood/article/129/1/30/35839/Classification-systems-for-chronic-graft-versus Shimoni A, Radici V, Nagler A. Conditioning. In: Sureda A, Corbacioglu S, Greco R, Kröger N, Carreras E, editors. The EBMT Handbook:Hematopoietic Cell Transplantation and Cellular Therapies [Internet]. Cham: Springer International Publishing; 2024. p. 125–34. Available from: https://doi.org/10.1007/9783031440809_13 Additional Declarations The authors have declared there is NO conflict of interest to disclose. Cite Share Download PDF Status: Under Review Version 1 posted Review # 2 received at journal 24 Apr, 2026 Reviewer # 2 agreed at journal 23 Apr, 2026 Reviewer # 1 agreed at journal 23 Apr, 2026 Reviewers invited by journal 02 Apr, 2026 Submission checks completed at journal 02 Apr, 2026 First submitted to journal 02 Apr, 2026 Unknown event 02 Feb, 2026 Editor assigned by journal 02 Feb, 2026 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. 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Dubai","correspondingAuthor":false,"prefix":"","firstName":"Mariam","middleName":"","lastName":"Alamin","suffix":""},{"id":616687949,"identity":"95cbbc15-f04c-4e26-9f0c-6f1600e8152c","order_by":6,"name":"Charmain Campbell","email":"","orcid":"","institution":"American Hospital Dubai","correspondingAuthor":false,"prefix":"","firstName":"Charmain","middleName":"","lastName":"Campbell","suffix":""},{"id":616687950,"identity":"abc1f48d-bda2-4a1e-9a31-751605e65e21","order_by":7,"name":"Nabeel Bader","email":"","orcid":"","institution":"American Hospital Dubai","correspondingAuthor":false,"prefix":"","firstName":"Nabeel","middleName":"","lastName":"Bader","suffix":""},{"id":616687951,"identity":"c08823a8-2681-406d-9802-e119542dc9e0","order_by":8,"name":"Alexandros Kanellopoulos","email":"","orcid":"https://orcid.org/0000-0002-7400-5416","institution":"Sheffield Teaching Hospitals NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Alexandros","middleName":"","lastName":"Kanellopoulos","suffix":""}],"badges":[],"createdAt":"2026-02-02 07:46:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8761905/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8761905/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106534501,"identity":"44fe2d37-ec87-445b-8b18-ad6f91761375","added_by":"auto","created_at":"2026-04-09 15:03:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60126,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier overall survival (1-year OS, 2-year OS, 5-year OS)\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8761905/v1/fb88bc1062dec4f0d8de5335.jpg"},{"id":106534503,"identity":"df76d4c8-5172-4a6d-9bf0-bbc1257e1f1f","added_by":"auto","created_at":"2026-04-09 15:03:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56112,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier progression-free survival (1-year PFS, 2-yearPFS, 5-yearPFS)\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8761905/v1/57cf8a66596dd381011be35d.jpg"},{"id":106534504,"identity":"eb37da4d-2322-4556-b2d4-86eb8c1e0ab2","added_by":"auto","created_at":"2026-04-09 15:03:54","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57731,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve with and without DLI\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8761905/v1/3bacc8c0b5f68a6af418b807.jpg"},{"id":106724866,"identity":"eacf3e10-eb88-4912-9550-dbfed4dc1785","added_by":"auto","created_at":"2026-04-12 18:30:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":726036,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8761905/v1/b0abf10a-e2f6-4aca-b18f-1629a13572da.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Reduced Intensity T-Replete Allogeneic Stem Cell Transplantation Provides Long-Term Survival in Relapsed Angioimmunoblastic T-Cell Lymphoma Post-Autologous Transplant in patients over the age of 50","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAngioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of primary nodal peripheral T-cell lymphoma (PTCL), accounting for approximately 1\u0026ndash;2% of all non-Hodgkin lymphomas (NHLs) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The majority of patients present with advanced disease, frequently manifesting as generalized lymphadenopathy, hepatosplenomegaly, and hypergammaglobulinemia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Even when AITL is treated with intensive induction regimens, the prognosis can be poor. Standard first-line therapy typically consists of anthracycline-based chemotherapy, with or without etoposide, depending on the patient\u0026rsquo;s age, and, for those who are CD30 positive, brentuximab combined with chemotherapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients who achieve complete remission (CR) and have a favorable performance status often proceed with autologous hematopoietic cell transplantation (auto-HCT) consolidation to achieve long term remission.\u003c/p\u003e \u003cp\u003eDespite this approach, outcomes remain unsatisfactory due to significant relapse rates[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Allogeneic hematopoietic cell transplantation (allo-HCT) has emerged as a potentially curative strategy for patients with relapsed AITL following auto-HCT [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], possibly owing to the graft-versus-lymphoma (GVL) effect mediated by donor immune cells [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. AITL originates from follicular helper T-cells and is characterized by immune dysregulation and EBV-induced B-cell proliferation, factors that may influence the response to immune-mediated GVL effects [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Allogeneic grafts can be categorized as T-cell-replete or T-cell-depleted depending on whether donor T-cells remain in the graft or are eliminated. T-depleted techniques minimize the risk of graft-versus-host disease (GvHD), but they may compromise disease control. On the other side, T-replete transplantation preserves donor T-cells, which can mediate a positive GVL effect but at the expense of increased GvHD risk [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDonor lymphocyte infusion (DLI), which can employ donor immune cells to improve disease control in certain hematologic malignancies, including AITL, may also be beneficial for treating relapse following allogeneic stem cell transplantation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Reduced-intensity conditioning (RIC) regimens, being less toxic and intense, allo-HCT to be offered to older or frail patients while preserving graft immunologic function [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Nevertheless, few studies have specifically evaluated reduced-intensity, T-replete allo-HCT in this setting, and the evidence for an early GVL effect remains limited.\u003c/p\u003e \u003cp\u003eIn an effort to channel a potential graft-versus-lymphoma effect following previous unsuccessful auto-HCT, we examined the therapeutic role of reduced-intensity, T-replete allogeneic transplantation in patients over 50 with relapsed AITL who achieved a chemo sensitive response to salvage therapy.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Patient Population\u003c/h2\u003e \u003cp\u003eThis was a retrospective, multicenter cohort study designed to evaluate the efficacy of reduced-intensity, T-replete allogeneic hematopoietic cell transplantation in patients with relapsed angioimmunoblastic T-cell lymphoma. The study included three bone marrow transplant (BMT) centers and comprised 21 patients who underwent allo-HCT following prior autologous HCT between 2013 and 2019. All patients were aged 50 years and above at the time of diagnosis and had experienced relapse after auto-HCT. Patients received salvage chemotherapy with GDP (gemcitabine, dexamethasone, cisplatin), ICE (ifosfamide, carboplatin, etoposide), or mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Those achieving complete response (CR) or partial response (PR) to salvage therapy were considered chemosensitive and were eligible for transplantation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eResponse Evaluation and Definitions\u003c/h3\u003e\n\u003cp\u003ePre-transplant response to salvage chemotherapy was assessed using \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT. Patients who demonstrated a complete or partial metabolic response by PET criteria [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] proceeded to reduced-intensity T-replete allo-HCT. The following endpoints were established according to the Revised Response Criteria for Malignant Lymphoma [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Overall survival (OS) was defined as the time between stem cell transplantation and death from any cause. Progression-free survival (PFS) was defined as the time between stem cell transplantation and lymphoma relapse, progression, or death from any cause, whichever occurred first. Non-relapse mortality (NRM) was defined as death from any cause without prior disease progression. Acute (grades I-IV) and chronic (limited or extensive) graft-versus-host disease (GvHD) were graded according to international consensus standards [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eTransplant Procedure\u003c/h3\u003e\n\u003cp\u003eAmong the 21 patients included in this study, 15 were males, and 6 were females, with a median age of 58.3 years (50\u0026ndash;73). Eight patients were in partial remission, and thirteen were in complete remission at the time of transplantation, based on PET/CT criteria. Five patients received an HLA-matched sibling allogeneic transplant, and sixteen received a fully matched volunteer unrelated donor transplant. Eligible donors were matched at the allele level for HLA-A, -B, -C, -DQ, and -DRB1. The conditioning regimen was classified as reduced-intensity according to the established EBMT criteria [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and consisted of fludarabine, cyclophosphamide, and a single fraction 2Gy total body irradiation (TBI). In total, 5 patients received donor lymphocyte infusion (DLI) at a dose of 1 x 10^6 cells/kg for post-transplant relapse.\u003c/p\u003e \u003cp\u003eAll patients received peripheral blood stem cell transplants. The median infused stem cell dose was 4.7X 10\u003csup\u003e6\u003c/sup\u003e CD34/kg (4.0-6.2 x 10\u003csup\u003e6\u003c/sup\u003e CD34/kg). Neutrophil engraftment was defined as an absolute neutrophil count (ANC) greater than 0.5 X 10\u003csup\u003e9\u003c/sup\u003e/L for two consecutive days following allo-HCT, and platelet engraftment as a platelet count greater than 20 X 10\u003csup\u003e9\u003c/sup\u003e/L for two consecutive days, unsupported. Cyclosporine and methotrexate were used for graft-versus-host disease (GvHD) prophylaxis.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eA descriptive analysis was initially performed to summarize the demographic and clinical characteristics of the study population. Patients were censored at the date of last contact for survival analyses. Median age and ranges were reported, along with transplantation- and treatment-related characteristics. Survival outcomes were assessed using the Kaplan\u0026ndash;Meier method. Overall survival (OS) was estimated from the date of transplantation until the date of death due to any cause or the last follow-up. Progression-free survival (PFS) was defined as the time between transplantation and disease progression, relapse, or death, whichever came first. Survival probabilities at 1, 2, and 5 years were estimated using 95% confidence intervals. Comparisons of survival between patient subgroups (e.g., patients receiving donor lymphocyte infusion versus those who did not) were conducted using the log-rank test. Mortality analysis was further performed to classify deaths into disease progression and HSCT-related mortality. Engraftment kinetics and graft-versus-host disease (GvHD) incidence were also reported descriptively. All statistical analyses were performed using R version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria) within the RStudio environment. A two-sided significance level of α\u0026thinsp;=\u0026thinsp;0.05 was applied throughout.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthical Issues\u003c/h3\u003e\n\u003cp\u003e The study was conducted in accordance with the Declaration of Helsinki and approved by the institutional review boards of all participating BMT centers. Informed consent for data use was obtained according to institutional policy. All patient data were anonymized prior to analysis to ensure confidentiality.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe dataset included 21 patients with relapsed AITL who received allogeneic stem cell transplantation following a previous autologous transplant. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the demographic and clinical characteristics of patients. The median age at diagnosis was 61 years (40\u0026ndash;73), with a male predominance (n\u0026thinsp;=\u0026thinsp;15). The median follow-up after allogeneic transplantation was 7.55 years (0.3\u0026ndash;10.7). Cytogenetic analysis was normal in most patients (n\u0026thinsp;=\u0026thinsp;15), while isolated abnormalities were less common and included 5q gain (n\u0026thinsp;=\u0026thinsp;3), 13q changes (n\u0026thinsp;=\u0026thinsp;2), and gain of chromosome 21 (n\u0026thinsp;=\u0026thinsp;1). The median infused stem cell dose was 5x10\u003csup\u003e6\u003c/sup\u003e (3.9-6.2x10\u003csup\u003e6\u003c/sup\u003e). Patients mostly received grafts from unrelated donors (n\u0026thinsp;=\u0026thinsp;16), while 5 had sibling donors. Donor\u0026ndash;recipient CMV serostatus was concordantly positive in 10 cases and negative in 5, with 6 pairs showing discordance (either donor/recipient positive). In total, 14 out of 21 patients were CMV seropositive. Donor lymphocyte infusion (DLI) was administered in 5 patients. All patients achieved hematologic engraftment, both for neutrophils and platelets. Median neutrophil engraftment occurred on day\u0026thinsp;+\u0026thinsp;17 (D\u0026thinsp;+\u0026thinsp;14 - D\u0026thinsp;+\u0026thinsp;25) and median platelet engraftment occurred on day\u0026thinsp;+\u0026thinsp;20 (D\u0026thinsp;+\u0026thinsp;18 - D\u0026thinsp;+\u0026thinsp;26). Ten patients experienced acute GvHD (grades I\u0026ndash;III), while 11 had no acute GvHD. Chronic GvHD occurred in 4 patients (all limited). In total, 13 patients (62%) had a complete metabolic response, and 8 patients (38%) had a partial metabolic response to salvage chemotherapy prior to allogeneic transplant. There were 7 deaths, 4 of which were due to disease progression, and 3 were HSCT-related.\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\u003ePatients\u0026rsquo; characteristics\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\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at diagnosis\u003c/p\u003e \u003cp\u003eFollow-up (in years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (40\u0026ndash;73)\u003c/p\u003e \u003cp\u003e7.55 (0.3\u0026ndash;10.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytogenetics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 gain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13q\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGain 21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStem cell dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5x10\u003csup\u003e6\u003c/sup\u003e (3.9\u0026ndash;6.2 x 10\u003csup\u003e6\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDonor type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSibling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnrelated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDonor/Recipient CMV status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEither donor/recipient +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMV status (patient)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMV status (donor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDonor DLI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEngraftment\u003c/p\u003e \u003cp\u003eNeutrophil Engraftment\u003c/p\u003e \u003cp\u003ePlatelet Engraftment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u0026thinsp;+\u0026thinsp;17 (D\u0026thinsp;+\u0026thinsp;14 - D\u0026thinsp;+\u0026thinsp;25)\u003c/p\u003e \u003cp\u003eD\u0026thinsp;+\u0026thinsp;20 (D\u0026thinsp;+\u0026thinsp;18 - D\u0026thinsp;+\u0026thinsp;26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute GvHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic GvHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimited\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetabolic Response\u003c/p\u003e \u003cp\u003eComplete\u003c/p\u003e \u003cp\u003ePartial\u003c/p\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCause of death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSCT related\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eRelapse and Non-Relapse Mortality\u003c/h3\u003e\n\u003cp\u003eAt the latest follow-up, 7 patients (33%) had passed away and 14 patients (67%) were still alive. Analysis of the cohort's mortality causes showed that, of the 7 patients with a documented cause of death, 4 (57.1%) died due to disease progression, and 3 (42.9%) succumbed as a result of hematopoietic stem cell transplantation (HSCT), indicating non-relapsed mortality. The median time to relapse among relapsed cases was 22 months (8\u0026ndash;92 months) following transplantation. These findings highlight the substantial impact that transplantation-related complications and disease progression have on patient survival.\u003c/p\u003e\n\u003ch3\u003eOverall Survival\u003c/h3\u003e\n\u003cp\u003eThe Kaplan-Meier overall survival analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) showed OS rates of 100% at 1 year, 81% at 2 years, and 71% at 5 years. The survival probability remains high for the first year, followed by a gradual decline over the 5-year follow-up period.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eProgression-Free Survival\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e depicts a Kaplan-Meier analysis of PFS, which revealed a probability of 95% at 1 year, 95% at 2 years, and 84% at 5 years. The survival curve remains steady for the first two years but declines after five years, indicating disease progression in a subset of patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAcute and Chronic GvHD\u003c/h2\u003e \u003cp\u003eAt three months post transplant, the cumulative incidence of grade II-IV acute GvHD was 38% (95% CI 32\u0026ndash;45), and grade III-IV acute GvHD was 15% (95% CI 8\u0026ndash;21). Acute GvHD predominantly affects the skin, gastrointestinal tract, and liver. The 1-year cumulative incidence of chronic GvHD was 46% (95% CI 39\u0026ndash;54), while the 1-year cumulative incidence of extensive chronic GvHD was 35% (95% CI 29\u0026ndash;44).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eDLI \u0026amp; Survival\u003c/h2\u003e \u003cp\u003eKaplan-Meier survival analysis comparing patients who received DLI versus those who did not (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) showed a trend toward improved survival in the DLI group. Although this difference was not statistically significant (log-rank test, p\u0026thinsp;=\u0026thinsp;0.5544), DLI appeared to contribute to durable immune-mediated disease control. Among DLI recipients, 4 of them (80%) remained alive at the end of the follow-up, while one (20%) experienced HSCT-related mortality.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective multicenter cohort study, reduced intensity T-replete allogeneic stem cell transplantation showed promising long-term survival in patients with relapsed AITL following prior autologous transplantation, a population that has traditionally been linked to few therapeutic options and poor outcomes. Of the 21 individuals in this sample, 8 achieved a partial metabolic response while 13 achieved a complete response. All patients achieved hematologic engraftment, and both OS (100% at 1 year and 71% at 5 years) and PFS (95% at 1\u0026ndash;2 years and 84% at 5 years) remained high during the early post-transplant period, suggesting that elderly patients with chemosensitive relapse may benefit from the potentially curative approach of T-replete grafts. At the end of the study, 7 patients had died; disease progression accounted for 57.1% of these deaths, while HSCT-related causes (non-relapsed mortality) accounted for the remaining instances.\u003c/p\u003e \u003cp\u003eSeveral factors may have contributed to the favorable outcomes observed. Firstly, all patients proceeded to transplantation with chemosensitive disease, which has been consistently associated with an improved post-transplant outcome in T-cell lymphomas, including AITL. Achieving a complete or partial remission prior to allo-HCT may have decreased disease burden, allowing donor immune reconstitution in the context of minimal residual lymphoma. Moreover, the use of a T-replete graft may have preserved donor T-cell function, supporting a stronger immunologic GvL effect. The early disease control, together with sustained remission observed in a significant portion of patients, supports the hypothesis that donor immune activity plays a critical role in long term lymphoma eradication. The universal engraftment and prompt neutrophil and platelet recovery further suggest the viability of allo-HCT in older transplant candidates over the age of 50.\u003c/p\u003e \u003cp\u003eWhen compared to previous research, the results of our study appear promising. Epperla et al. achieved in their research a 4-year OS of 56% and PFS of 47\u0026ndash;49% in relapsed AITL following allo-HCT, while Kyriakou et al. demonstrated durable remission although with more heterogeneous conditioning regimens. The improved survival rates observed in our cohort could be related to the combination of chemosensitive disease at transplantation and a uniform reduced-intensity T-replete transplant strategy. This highlights again the need of preserving donor T-cells for the development of an early and clinically relevant GvL response. In general, our findings indicate that for those patients with relapsed AITL who respond to salvage therapy, reduced-intensity T-replete allo-HCT may provide a viable option to long-term remission even if autologous transplant fails. Despite the sample size being limited, the increased survival observed in patients receiving DLI supports the notion that immune-mediated disease control may play an important role in this context.\u003c/p\u003e \u003cp\u003eAlthough these findings are promising, GvHD still remained a transplant-related risk, with both acute and chronic GvHD observed in the study. The occurrence of GvHD reflects the inherent balance between desirable GvL activity and unwanted immune toxicity. Nonetheless, non-relapse mortality in older allo-HCT recipients remained limited relative to historical expectations, indicating that reduced-intensity conditioning may decrease toxicity while preserving immunologic benefit.\u003c/p\u003e \u003cp\u003eThe limitations of this study should be taken into consideration. Our findings have limited generalizability due to the intrinsic retrospective study design and the small sample size used in this research. Furthermore, due to a lack of molecular or genomic patient data, biological predictors of allo-HCT response cannot be established. This study only included chemosensitive patients, which could introduce selection bias toward favorable biology or treatment response. Future prospective multicenter studies should be conducted to confirm these findings, investigate biomarkers of transplant response, and optimize approaches that improve GvL activity while minimizing GvHD-related morbidity.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAITL has an uncertain prognosis when treated with conventional therapies, hence novel approaches are needed. This research comprised patients over the age of 50 who have relapsed AITL after autologous transplantation and for whom reduced-intensity T-replete allogeneic stem cell transplantation yields promising OS and PFS outcomes. Hematologic engraftment was achieved in all patients, suggesting that this approach is feasible even in elderly populations. This study demonstrates that the T-replete approach may offer long-term survival and induce an early GVL effect to the patients. Moreover, reduced-intensity conditioning can balance toxicity while preserving the donor immune function. Therefore, donor-derived immune activity is crucial to maintaining remission as seen by the favorable results achieved in patients receiving DLI. Due to the disease's rarity and the limited data given, new and larger research studies, possibly with integrated biologic profiling, are required to confirm our findings and identify effective strategies that preserve GVL effect while diminishing GvHD.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ed\u0026rsquo;Amore F, Gaulard P, Tr\u0026uuml;mper L, Corradini P, Kim WS., Specht L, et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [Internet]. 2015;26:v108\u0026ndash;15. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.annalsofoncology.org/article/S0923-7534(\u003c/span\u003e\u003cspan address=\"https://www.annalsofoncology.org/article/S0923-7534(\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e19)47172-X/pdf\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFederico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, et al. Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project. Journal of Clinical Oncology. 2013;31(2):240\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMourad N, Mounier N, Bri\u0026egrave;re J, Raffoux E, Delmer A, Feller AC, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d\u0026rsquo;Etude des Lymphomes de l\u0026rsquo;Adulte (GELA) trials. BLOOD. 2008;111(9):4463\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharalampia Kyriakou, Canals C, Goldstone A, Caballero D, Metzner B, Kobbe G, et al. High-Dose Therapy and Autologous Stem-Cell Transplantation in Angioimmunoblastic Lymphoma: Complete Remission at Transplantation Is the Major Determinant of Outcome\u0026mdash;Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of Clinical Oncology. 2007;26(2):218\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEpperla N, Ahn KW, Litovich C, Ahmed S, Battiwalla M, Cohen JB, et al. Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis. Journal of Hematology \u0026amp; Oncology. 2019;12(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharalampia Kyriakou, Canals C, Finke J, Kobbe G, Jean-Luc Harousseau, Kolb H, et al. Allogeneic Stem Cell Transplantation Is Able to Induce Long-Term Remissions in Angioimmunoblastic T-Cell Lymphoma: A Retrospective Study From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of Clinical Oncology. 2009;27(24):3951\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelioukina M, Zain J, Palmer JM, Tsai N, Thomas S, Forman S. Reduced-intensity allogeneic hematopoietic cell transplantation using fludarabine\u0026ndash;melphalan conditioning for treatment of mature T-cell lymphomas. Bone Marrow Transplantation. 2011;47(1):65\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMamez AC, Dupont A, Blaise D, Chevallier P, Forcade E, Ceballos P, et al. Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Soci\u0026eacute;t\u0026eacute; Francophone de Greffe de Moelle et de Th\u0026eacute;rapie Cellulaire (SFGM-TC). Journal of Hematology \u0026amp; Oncology. 2020;13(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamadani M, Awan FT, Elder P, Lin TS, Peirluigi Porcu, Blum KA, et al. Allogeneic Hematopoietic Stem Cell Transplantation for Peripheral T Cell Lymphomas; Evidence of Graft-Versus-T Cell Lymphoma Effect. Biology of Blood and Marrow Transplantation. 2008;14(4):480\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorradini P, Dodero A, Zallio F, Caracciolo D, Casini M, Bregni M, et al. Graft-Versus-Lymphoma Effect in Relapsed Peripheral T-Cell Non-Hodgkin\u0026rsquo;s Lymphomas After Reduced-Intensity Conditioning Followed by Allogeneic Transplantation of Hematopoietic Cells. Journal of Clinical Oncology. 2004;22(11):2172\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeng Y, Ma Y, Li T, Liu M, Hong Z, Yin Q, et al. Angioimmunoblastic T-cell lymphoma: a concise overview encompassing the pathogenetic, pathological, clinical, therapeutical characteristics, and recent advances. Clinical and Experimental Medicine. 2025;25(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, et al. Improved Early Outcomes Using a T Cell Replete Graft Compared with T Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation. 2012;18(12):1835\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodriguez R, Auayporn Nademanee, Ruel N, Smith E, Krishnan A, Popplewell L, et al. Comparison of Reduced-Intensity and Conventional Myeloablative Regimens for Allogeneic Transplantation in Non-Hodgkin\u0026rsquo;s Lymphoma. Biology of Blood and Marrow Transplantation. 2006;12(12):1326\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised Response Criteria for Malignant Lymphoma. Journal of Clinical Oncology [Internet]. 2007;25(5):579\u0026ndash;86. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://imaging.cancer.gov/clinical_trials/docs/Cheson%20(IWG)%20Criteria%20JCO%202007.pdf\u003c/span\u003e\u003cspan address=\"https://imaging.cancer.gov/clinical_trials/docs/Cheson%20(IWG)%20Criteria%20JCO%202007.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. Journal of Clinical Oncology. 2014;32(27):3059\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrzepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplantation [Internet]. 1995;15(6):825\u0026ndash;8. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/7581076/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/7581076/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee SJ. Classification systems for chronic graft-versus-host disease. Blood [Internet]. 2017;129(1):30\u0026ndash;7. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ashpublications.org/blood/article/129/1/30/35839/Classification-systems-for-chronic-graft-versus\u003c/span\u003e\u003cspan address=\"https://ashpublications.org/blood/article/129/1/30/35839/Classification-systems-for-chronic-graft-versus\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShimoni A, Radici V, Nagler A. Conditioning. In: Sureda A, Corbacioglu S, Greco R, Kr\u0026ouml;ger N, Carreras E, editors. The EBMT Handbook:Hematopoietic Cell Transplantation and Cellular Therapies [Internet]. Cham: Springer International Publishing; 2024. p. 125\u0026ndash;34. Available from: https://doi.org/10.1007/9783031440809_13\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8761905/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8761905/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRelapsed angioimmunoblastic T-cell lymphoma (AITL) following autologous transplantation carries poor prognosis. Reduced-intensity T-replete allogeneic transplant may provide durable disease control via immune-mediated graft effects.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 21 patients over the age of 50 with relapsed AITL who underwent reduced-intensity T-replete allo-HCT across three transplant centers between 2013 and 2022. Following salvage treatment, all patients experienced chemo sensitive disease and proceeded to transplantation. Responses were PET-based, and survival outcomes were assessed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAll patients achieved hematologic engraftment, with 13 in complete metabolic remission and 8 in partial remission at the time of transplant. At a median follow-up of 7.55 years, OS was 100%, 81%, and 71% at 1, 2, and 5 years, respectively, with PFS of 95%, 95%, and 84%. Seven deaths occurred, four due to disease progression and three related to transplantation. Acute and chronic GvHD were observed in 30% and 22% of patients respectively. Five patients received donor lymphocyte infusion, showing a trend toward improved survival.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eReduced-intensity T-replete allo-HCT is a feasible and potentially curative therapeutic option for patients over 50 with chemo sensitive relapsed AITL after autologous transplantation. Early disease control and long-term remission suggest a clinically meaningful graft-versus-lymphoma (GVL) effect in appropriately selected individuals.\u003c/p\u003e","manuscriptTitle":"Reduced Intensity T-Replete Allogeneic Stem Cell Transplantation Provides Long-Term Survival in Relapsed Angioimmunoblastic T-Cell Lymphoma Post-Autologous Transplant in patients over the age of 50","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 15:03:50","doi":"10.21203/rs.3.rs-8761905/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-04-24T15:40:17+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-23T16:43:31+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-23T14:39:34+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-04-02T14:35:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-02T12:59:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bone Marrow Transplantation","date":"2026-04-02T09:02:28+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-02-02T10:32:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-02T07:44:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d6425393-c7bb-4daa-b881-663573424e89","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65625005,"name":"Health sciences/Diseases/Haematological diseases/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/T-cell lymphoma"},{"id":65625006,"name":"Health sciences/Diseases/Cancer/Cancer therapy"}],"tags":[],"updatedAt":"2026-04-09T15:03:50+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 15:03:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8761905","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8761905","identity":"rs-8761905","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}