The notable outcomes of modified thiotepa-based conditioning followed by autologous stem cell transplantation in primary central nervous system lymphomas: A real-life pilot study

The notable outcomes of modified thiotepa-based conditioning followed by autologous stem cell transplantation in primary central nervous system lymphomas: A real-life pilot study | 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 The notable outcomes of modified thiotepa-based conditioning followed by autologous stem cell transplantation in primary central nervous system lymphomas: A real-life pilot study Yan Li, Sen Li, Fang Bao, Lan Ma, Wei Zhao, Ping Yang, Fei Dong, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4403718/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract High-dose chemotherapy followed by autologous stem cell transplantation (HDC–ASCT) is a promising approach for patients with primary central nervous system lymphoma (PCNSL). Encouraging results have been reported with thiotepa-based conditioning; however, there is currently no consensus on the optimal conditioning regimens. To improve the tolerance and efficacy of ASCT with thiotepa-based conditioning, this retrospective, single-arm, pilot study was conducted, including 12 PCNSL patients who received ASCT with modified thiotepa-based conditioning regimens. It was found that 6 patients received ASCT as a first-line consolidation in complete response (CR)/partial response (PR) state, and 6 cases underwent salvage treatment. Among the patients, 7 (58.3%) received the mTBC conditioning regimen, 4 (33.3%) received TT-Bu, and one patient was incorporated with chimeric antigen receptor T-cell (CAR-T) cell infusion with the TT-Cy regimen. All patients achieved sustained neutrophil recovery within a median of 9 (range, 7–12) days and platelet engraftment within a median of 10 (range, 6–12) days. Furthermore, all patients were in CR status at the initial efficacy evaluation following ASCT. The main complications during hospitalization were febrile neutropenia (83.3%) and diarrhea grade 3 (50.0%). No transplantation- related mortality occurred. Maintenance therapy post-ASCT was administered in 11 cases, demonstrating its effectiveness and favorable tolerability. The estimated 1- and 3-year progression-free survival (PFS) following ASCT were 80.0% and 53.3%, respectively, while the estimated 1-and 3-year overall survival (OS) were both 100%. This study presented the modified thiotepa-based conditioning regimens and confirmed their safety and efficacy with ASCT for PCNSL patients. primary central nervous system lymphoma thiotepa-based conditioning high dose chemotherapy autologous stem cell transplantation Figures Figure 1 Figure 2 Introduction Primary central nervous system lymphoma (PCNSL) is an aggressive, heterogeneous, and rare neoplasm of extra-nodal non-Hodgkin lymphoma (NHL), developing in the brain, spinal cord, cranial nerves, leptomeninges and vitreo-retina [ 1 – 4 ]. PCNSL is mainly diffuse large B-cell lymphomas (DLBCLs) of the activated B-cell (ABC) subtype, associating with a poor prognosis [ 1 , 5 , 6 ]. Several clinical trials have demonstrated the benefit of high-dose chemotherapy (HDC) for PCNSL patients, followed by HDC-autologous stem cell transplantation (HDC-ASCT) [ 7 , 8 ]. Several clinical consensus/guidelines recommend HDC-ASCT as consolidation therapy for younger patients (up to age 65–70) with newly-diagnosed PCNSL, or as salvage treatment for relapsed/refractory PCNSL [ 9 – 14 ]. According to the efficient penetration of the blood-brain barrier (BBB), high-dose thiotepa-based conditioning chemotherapy has been proposed for PCNSL [ 1 , 10 ], while the carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen widely used in systemic lymphomas was confirmed with suboptimal disease control for PCNSL [ 15 – 17 ]. However, there are still gaps in knowledge and unmet needs regarding the lack of consensus on the appropriate thiotepa-based regimens. The thiotepa, busulfan, and cyclophosphamide (TBC) conditioning regimen exhibited higher rates of progression-free survival (PFS) and transplantation- related mortality (TRM) compared with thiotepa and carmustine (TT-BCNU). This counteracted the potential benefit of PFS leading to no overall survival (OS) advantage [ 17 ]. Therefore, dose adjustment of the conditioning regimen is essential. The present study, aimed to optimize this strategy utilizing the reduced intensity, modified thiotepa-based conditioning regimen for PCNSL patients receiving ASCT to improve the tolerance and efficacy of ASCT. Methods Patients This retrospective, real-life pilot study involved a total of 12 patients with PCNSL who received ASCT based on modified thiotepa-based conditioning regimens in our center between March 2021 and December 2023. All patients survived and were followed up until January 31, 2024, with a median follow-up time of 135 days (range, 57–1014) following transplantation. Conditioning regimen and ASCT The commonly used TBC regimens consisted of intravenous thiotepa (250 mg/m 2 /d, D-9 through D-7), busulfan (3.2 mg/kg/d, D-6 through D-4), and cyclophosphamide (60 mg/kg/d, D-3, D-2), followed by ASCT on D0. The reduced intensity chemotherapy included TT-Bu (thiotepa, 300 mg/m 2 /d, D-6, D-5, busulfan, 3.2 mg/kg/d, D-4 through D-2, and TT-BCNU (thiotepa, 400 mg/m 2 /d, D-6, carmustine, 5 mg/kg/d, D-5, D-4), as described previously [ 18 – 22 ]. In this study, the modified thiotepa-based conditioning regimens, consisted of mTBC (thiotepa, 300 mg/m 2 /d, D-8 and D-7, busulfan, 3.2 mg/kg/d, D-6 through D-4, and cyclophosphamide, 1 g/m 2 /d, D-3 and D-2) with stem cell reinfusion on day 0, TT-Bu (thiotepa, 300 mg/m 2 /d, D-8 and D-7, busulfan, 3.2 mg/kg/d, D-6 through D-4) for ASCT in patients with fragile conditions, and TT-Cy (thiotepa, 300 mg/m 2 /d, D-5 and D-4, cyclophosphamide, 1 g/m 2 /d, D-3 and D-2) for ASCT incorporated with chimeric antigen receptor T-cell (CAR-T) therapy (Table 1 ). Planned CD19 CAR-T therapy involved ASCT incorporated with CAR-T cell infusion on d + 3, and individual CAR-T therapy was considered as consolidation in the early phase post-ASCT for progressive patients before ASCT. The selection of different strategies depended on the patient’s preferences and the discretion of the treating physician. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 were utilized to identify grade 3–5 toxicities associated with ASCT. Supportive therapy followed institutional guidelines, including granulocyte stimulating factor, seizure and infection prophylaxis, hydration, antiemesis, and irradiated blood products. Table 1 Thiotepa-based conditioning regimens for ASCT recipients with PCNSL Regimens carmustine thiotepa busulfan cyclophosphamide Reference TBC / 250 mg/m 2 /d, d-9, -8, -7 3.2 mg/kg/d, d-6, -5, -4 60 mg/kg/d, d-3, -2 18–20 TT-Bu / 300 mg/m 2 /d, d-6, -5 3.2 mg/kg/d, d-4, -3, -2 / 21 TT-BCNU 400mg/m 2 /d, d-6 5 mg/kg/d, d-5,-4 / / 22, 23 mTBC / 300 mg/m 2 /d, d-8, -7 3.2 mg/kg/d, d-6, -5, -4 1g /m 2 /d, d-3, -2 / TT-Cy a / 300 mg/m 2 /d, d-5, -4 / 1 g/m 2 /d, d-3, -2 / a for ASCT incorporated with chimeric antigen receptor T-cell therapy ASCT , autologous stem cell transplantation; PCNSL , primary central nervous system lymphoma; TBC , thiotepa, busulfan, cyclophosphamide; mTBC , modified TBC; TT-BCNU , thiotepa, carmustine; TT-Bu , thiotepa, busulfan; TT-Cy , thiotepa, cyclophosphamide Efficacy evaluation and maintenance therapy Brain magnetic resonance imaging (MRI) with contrast-enhanced and diffusion-weighted imaging (DWI) employed for the diagnosis and assessment of treatment efficacy in PCNSL patients. Whole-body fluorodeoxyglucose positron emission tomography (PET) was utilized to evaluate PCNSL patients at cspecific time points, such as the time of initial diagnosis or at relapse in accordance with recommendations from consensus guidelines reported by the Chinese Neurosurgical Society of the Chinese Medical Association (CNSCMA) and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association (SHM-CACA) [ 10 ]. Besides, response assessment was conducted before transplantation, one month after ASCT, and then every 3 months until 2 years post-transplantation. Subsequent evaluations were scheduled every 6 months until 5 years and annually thereafter. In cases where MRI indicated progression or relapse, PET imaging was recommended. Treatment response for complete response (CR), unconfirmed complete response (CRu), partial response (PR), stable disease (SD), progressive disease (PD), and relapsed disease was assessed according to the guideline of the International PCNSL Collaborative Group (IPCG) for PCNSL [ 24 ]. Initiation of maintenance therapy is strongly recommended within 3 months after ASCT, and the therapy should be maintained for two years in this study unless there is disease progression, or intolerable toxicity. The selection of drugs for maintenance therapy is based on the physician’s recommendations, considering the patients’ prior treatment and their preferences. Statistical analysis The PFS was calculated as the duration from ASCT to the first time of progression, recurrence, death, or the last follow-up. The OS was defined as the time between ASCT and death from any cause or the last follow-up. TRM was defined as non-relapse-related deaths caused by transplantation occurring during and after ASCT. The time points before and after transplantation were presented by ‘-’ or ‘+’ signs. The demographic and clinical characteristics were summarized using descriptive statistics. Survival analysis was performed by the Kaplan–Meier method. The statistical analysis was carried out by SPSS 20.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism 7.0 (GraphPad Software Inc., San Diego, CA, USA) software. Results Demographic and clinical characteristics Data of 12 PCNSL patients who underwent ASCT with modified thiotepa-based conditioning regimens, including 5 men and 7women are presented in Table 2 Patients’ median age at the time of ASCT was 57.5 (range, 37‒66) years, of whom 2 (16.7%) patients aged ≥ 60 years. Moreover, 9 (75%) patients had and an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of ≥ 2 points at the time of diagnosis due to PCNSL symptoms. Notably, 91.7% (11/12) of patients had brain involvement, with 8 (66.7%) patients displaying multiple lesions. Additionally, 7 patients (58.3%) showed lesions in the deep brain structures, such as the basal ganglia, corpus callosum, brain stem, and cerebellum). Biopsy results were achieved for all patients, with 11 (91.7%) identified as the ABC subtype. Among 4 patients whose tumor tissues underwent targeted-mutation testing utilizing next-generation sequencing (NGS), MYD88 was the most common mutation occurring in all cases (100%, 4/4), followed by PIM1 in 75% (3/4) of cases (Table 3 ). Two-thirds of the patients had an elevated lactate dehydrogenase (LDH) level (LDH ≥ 246 U/L ). However, due to the poor status of patients at diagnosis, only half of the patients underwent lumbar puncture and cerebrospinal fluid (CSF) examination. Among 6 patients with available CSF protein data, all had normal CSF protein level. Two of the remaining six patients without CSF protein data could not be evaluated using the PCNSL prognosis system established by the International Extranodal Lymphoma Study Group (IELSG). In 10 patients, 3 (30%) were categorized as low-risk, and 7 (70%) were categorized as intermediate-risk according to the IELSG score. Table 2 Clinical characteristics of HDC-ASCT recipients with PCNSL (n = 12) Characteristics N = 12, % Age at ASCT, years, median (range) 57.5 (37, 66) Age at ASCT < 60 years 10 (83.3) ≥ 60 years 2 (16.7) Gender Male 5 (41.7) Female 7 (58.3) ECOG-PS at diagnosis 0–1 3 (25.0) ≥ 2 9 (75.0) Sites involved at diagnosis Brian 11 (91.7) Isolated CSF 0 (0.0) Isolated intraocular 1 (8.3) Lesions at diagnosis Single 4 (33.3) Multiple 8 (66.7) Involvement of deep brain structure a Yes 7 (58.3) No 5 (41.7) LDH Elevated 4 (33.3) Normal 8 (66.7) CSF protein Elevated 0 (0.0) Normal 6 (50.0) Missing 6 (50.0) Histology DLBCL-ABC 11 (91.7) DLBCL-GCB 1 (8.3) IELSG scoring system b 10 (83.3) Low risk (0–1) 3 (30.0) Intermediate risk (2–3) 7 (70.0) High risk (4–5 ) 0 (0.0) Prior treatment line 4 (14.3) One prior line 6 (50.0) Two prior lines 2 (16.7) More than two prior lines 4 (33.3) Prior radiotherapy 1 (8.3) Remission status at ASCT CR1 5 (41.7) PR 1 (8.3) ≥CR2 4 (33.3) PD 2 (16.7) ASCT strategy In first-line consolidative treatment 6 (50.0) Salvage treatment at relapse/refractory 6 (50.0) Time from diagnosis to ASCT, month, median (range) 10.2 (5.2-102.1) 12 5 (41.7) Conditioning regimen mTBC 7 (58.3) TT-Bu 4 (33.3) TT-Cy 1 (8.3) Graft MNCs, ×10 8 /kg, median (range) 4.57 (3.06–7.75) CD34+, ×10 6 /kg, median (range) 3.83 (1.1–9.51) Engraftment, days post ASCT ANC, median (range) 9 (7–12) PLT, median (range) 10 (6–12) a Involvement of deep structures of the brain, ie, basal ganglia and/or corpus callosum and/or brain stem and/or cerebellum b Two patients without CSF protein data could not be evaluated HDC-ASCT , high dose chemotherapy (HDC) followed by autologous stem cell transplantation; PCNSL , primary central nervous system lymphoma; ECOG-PS , Eastern Cooperative Oncology Group Performance Status; CSF , cerebrospinal fluid; LDH , lactate dehydrogenase; DLBCL , diffuse large B-cell lymphoma; ABC , activated B cell; GCB , germinal center B; IELSG , International Extranodal Lymphoma Study Group; CR , complete response; PR , partial response; PD , progressive disease; mTBC , modified thiotepa, busulfan, cyclophosphamide; TT-Bu , thiotepa, busulfan; TT-Cy , thiotepa, cyclophosphamide; MNCs , mononuclear cells; ANC , absolute neutrophil count; PLT , platelet Chemotherapy and outcomes before ASCT It was found that 6 patients received two or more lines chemotherapy pre-ASCT, of whom one patient received whole-brain radiotherapy (WBRT) due to disease progression. The median time from diagnosis to initial treatment was 24.5 (range, 1‒50) days. Patients’ detailed clinical data are presented in Table 3 . For first-line therapy, only one patient with isolated intraocular disease received a regimen of local methotrexate (MTX) combined with rituximab and lenalidomide (RL) regimen. High-dose-MTX (HD-MTX) based chemotherapy, ranging from 3.0 to 3.5 g/m 2 was the mainstay for the majority of patients (91.7%). The Bruton’s tyrosine kinase inhibitor (BTKi) was incorporated into the first-line therapy for 45.4% (5/11) of patients, and into second-line therapy for 66.7% (4/6) of patients with relapsed or refractory PCNSL (R/R PCNSL). Prior to transplantation, five patients achieved sustained CR, and one patient achieved PR. Forthermore, five patients experienced relapse but achieved CR with multi-course re-induction chemotherapy, while two patients had progressive disease until undergoing ASCT. The median number of total courses before ASCT was 7.5 (range, 6‒23) (Table 3 ). Table 3 Individual patient characteristics, previous treatments and outcome after transplantation (n = 12, FU to Jan. 31st, 2024) Pt Gender/age at HSCT Initial disease site Tissue gene mutations by NGS Initial treatment Duration of first response, mo. No. of relapse pre-HSCT Re-induction regimen and treatment Total courses pre-HSCT Remission status at HSCT Time from diagnosis to HSCT, mo. Conditioning regimen Maintenance treatment post-HSCT, drug, duration PFS from HSCT mo. OS status and duration from HSCT mo. Remission status at last follow-up 1 50/F Right eye a ND Local MTX, RL, 10 4 RL-MTX, E, Z, MA, R-Z + TMZ + E + Docorubicin + P b , MA b 23 CR5 32 mTBC Zanubrutinib, 8 mo. 35 Alive, 35 CR 2 56/F Brain-deep c ND R-MA, R-MA + TMZ, L 27 1 MTX + L + TMZ, RL-TMZ, R-CHOPE b 17 CR2 41 TT-Bu d Tislelizumab, 12 mo. Orelabrutinib, 8 mo. 18 Alive, 32 CR 3 43/M Brain-deep c ND R-MTX + TMZ, R-COPADM1 b / 0 / 6 CR1 5 mTBC None 6 Alive, 31 SD 4 58/M Brain-deep c ND R-MA, R-MTX + Ibrutinib, R-COPADM + Ore b / 0 / 7 CR1 7 mTBC Orelabrutinib + lenalidomide, 24 mo., continuing 27 Alive, 27 CR 5 37/M Brain MYD88 , PIM1 R-MTX + TMZ, R-MA b , MATRix / 0 / 6 CR1 7 mTBC Orelabrutinib, 2 mo. continuing 10 Alive, 10 CR 6 50/F Brain ND R-MAD, EA , , 5 1 Ore-MTDEA, modified TEDDi-R b , Ore-MTX + TMZ 11 CR2 11 TT-Bu d Orelabrutinib + lenalidomide, 3 mo., continuing 5 Alive, 5 CR 7 60/M Brain ND R-MTX + TMZ + vincristine + teniposide, MA 95 1 motdfied TEDDi-R b , R-MA, RL-Ore + Pemetrexed 13 PD 102 mTBC CD19 CAR-T 4 Alive, 4 CR 8 57/F Brain-deep c MYD88 Ore, R + MTX + TMZ Refractory disease, MATRix, modified TEDDi-R b , WBRT 7 PD 11 TT-Cy Orelabrutinib, 1 mo. 3 Alive, 3 CR 9 59/F Brain-deep c ND R-Z + MTX, modified TEDDi-R b , MATRix / 0 / 6 PR 7 mTBC Zanubrutinib, 8 days, continuing 3 Alive, 3 CR 10 59/F Brain BCL2 , MYD88 、 IRF4 , PIM1 R-MTX + vincristine, R-MTX + Ore, R-TMZ + Ore / 0 / 6 CR1 8 mTBC Orelabrutinib, 5 days, continuing 2 Alive, 2 CR 11 58/F Brain-deep c ND R-MTX, R- thiotepa + Ore, R-MA 6 2 TEDDi-R + selinexor b , L + Ore + selinexor, TEDDi-R, L + Ore + selinexor, WBRT 10 CR3 18 TT-Bu d Orelabrutinib, 12 days, continuing 2 Alive, 2 CR 12 . 66/M Brain-deep c CD79B , MYD88 , NOTCH1 , TP53 , PIM1, DNMT3A R-MTX + Ore, R-MTX + TMZ, R-THOP, R-MTX, TEDDi-R b , R-EPOCH ‡ / 0 / 8 CR1 10 TT-Bu d Orelabrutinib, 3 days, continuing 2 Alive, 2 CR a Brain was involved in the first relapse after one year b for mobilization of stem cells c according to IELSG scoring system, including basal ganglia, corpuscallosum, brain stem, cerebellum d TT-Bu for pt 2, pt 6, pt 11, and pt 12 due to post multi-course chemotherapy with poor tolerance, latent tuberculosis infection, myelosuppresion after radiotherapy, and age > 65 years old, respectively FU , follow up; Pt , patients number; NGS , next generation sequence; mo. Months; ASCT , autologous stem cell transplantation; ND , no data; CR , complete remission; PR , partial remission; PD , progressive disease; PFS , progression free survival; OS , overall survival; MTX , methotrexate; R , rituximab; L , lenalidomide; E , etoposide; Z , zanubrutinib; TMZ , temozolomide; P , prednisone; MA , methotrexate, cytarabine; R-CHOPE , rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide; R-COPADM1 , rituximab, cyclophosphamide, vincristine, prednisone, adriamycin, methotrexate; MATRix , rituximab, methotrexate, cytarabine, thiotepa; R-MAD, r ituximab, methotrexate, cytarabine, dexamethasone; Ore , orelabrutinib; Ore-MTDEA , orelabrutinib, methotrexate, temozolomide, dexamethasone; motified TEDDi-R , temozolomide, teniposide, doxorubicin, orelabrutinib/ zanubrutinib, dexamethasone, rituximab; R-THOP , rituximab, temozolomide, doxorubicin, vincristine,prednisone; R-EPOCH, r ituximab, etoposide, prednisone, doxorubicin, cyclophosphamide, vincristine; CAR-T , chimeric antigen receptor T-cell; WBRT , whole-brain radiotherapy; mTBC , modified thiotepa, busulfan, cyclophosphamide; TT-Bu , thiotepa, busulfan; TT-Cy, t hiotepa, cyclophosphamide ASCT and the associated complications The median time from diagnosis to ASCT was 10.2 (range, 5.2‒102.1) months, and only 7 (51%) patients received ASCT within one year of diagnosis. Six patients received ASCT as first-line consolidation in CR/PR state. Moreover, 7 (58.3%) patients received mTBC conditioning regimen, 4 (33.3%) received TT-Bu, and one patient received TT-Cy, incorporating CAR-T cell infusion. Among 4 patients receiving TT-Bu, a reduced toxicity regimen due to reasons, such as poor tolerance post multi-course chemotherapy, latent tuberculosis infection, myelosuppression after radiotherapy, and age over 65 years old, respectively. The median dose of mononuclear cells (MNCs) and CD34 + cells in the graft for infusion was 4.57 × 10 8 /kg (range, 3.06‒7.75) and 3.83 × 10 6 /kg (range, 1.1‒9.51), respectively. All patients achieved sustained neutrophil recovery at a median of 9 (range, 7–12) days and platelet engraftment at a median of 10 (range, 6–12) days (Table 2 ). All patients were in CR at the first efficacy evaluation following ASCT. With the modified thiotepa-based ASCT procedure, no TRM occurred. There was no hemorrhagic cystitis, sinusoidal obstruction syndrome (SOS), and cutaneous toxicity. The main complications during hospitalization were febrile neutropenia (83.3%) and diarrhea grade III (50.0%) (Table 4 ). There were 3 (25%) patients with temporally acute delirium, including delirium, photis, time and/or location disorientation, which occurred during intravenous busulfan. Furthermore, 2 (16.7%) patients experienced oral mucositis grade III (16.7%), and 2 (16.7%) cases were found with septicemia, including one with Escherichia coli, the other one with carbapenem-resistant Enterobacteriaceae (CRE), klebsiella pneumoniae (KP). Besides, each patient experienced an epileptic seizure and implantation syndrome, respectively (Table 4 ). All patients with these complications had favorable outcomes. Although no formal neurologic assessment was performed, no case of significant long-term cognitive dysfunction or decline was identified during follow-up. Table 4 Main complications during hospitalization for HDC-ASCT (n = 12) Complications N = 12, % Febrile neutropenia 10 (83.3) Diarrhea grade 3 6 (50.0) Acute delirium 3 (25.0) Oral mucositis grade 3 2 (16.7) Septicemia 2 (16.7) Epileptic seizure 1 (8.3) Implantation syndrome 1 (8.3) HDC-ASCT , high dose chemotherapy followed by autologous stem cell transplantation Maintenance therapy All patients, except one case, enderwent maintenance therapy, beginning at a median time of 62 (range, 30–245) days after ASCT. The majority (10/11, 90.9%) opted for BTKi, predominantly orelabrutinib (8/11, 72.7%) and zanubrutinib (2/11, 18.2%). One patient received individualized CD19 CAR-T therapy as consolidation on day + 49 post-ASCT due to progressive disease before the trasplant. At the last follow-up, only one patient, who had been on zanubrutinib for eight months, discontinued due to a COVID-19 infection during the pandemic. The median duration of maintenance therapy was 42 (range, 3–739) days, with 11 (91.7%) patients remaining in complete remission. The sole patient who declined maintenance therapy for financial reasons experienced a relapse on day + 181 post-ASCT. However, the disease has since stabilized with the use of a BTKi, knetinib in a clinical trial (Registration No. CTR20200412) (Table 3 ). Response and survival outcomes Treatment response and survival outcomes are vividly illustrated in the swimmer plots (Fig. 1 ). The total response rate of initial induction chemotherapy was high (10/12, 83.3%), while up to half of the patients (5/10, 50%) relapsed and 3 patients relapsed within one year. The salvage therapy for R/R PCNSL included multidrug combination chemotherapy, WBRT, and CAR-T (Table 3 ; Fig. 1 ). Notably, 3 patients received CAR-T therapy in different clinical conditions. One of the two patients who had progressive disease before ASCT received CAR-T cell infusion on + 3d post-ASCT, while the other patient underwent an individual CAR-T therapy as consolidation in the early post-ASCT phase. Another one received CAR-T therapy for late relapse on + 554d post-ASCT. All of these 3 patients obtained sustained CR (Fig. 1 ). The median follow-up time from initial treatment and ASCT was 19 (range, 8.9–106) and 4.5 (range, 1.9–34.7) months, respectively. The median OS from diagnosis was 19.1 (range, 10.2-106.6) months. The median PFS pre-ASCT was 8.3 (range, 5.2–96.8) months. Moreover, the median PFS and OS from ASCT were both 4.5 (range, 1.9–34.7) months (Table 3 ; Fig. 1 ). The estimated 1- and 3-year PFS rates were 80.0% and 53.3%, while the estimated 1- and 3-year OS rates were both 100% (Fig. 2 ). Discussion PCNSL is an aggressive lymphoma characterized with poor prognosis. HDC-ASCT as the first-line consolidation or salvage therapy can be a critical approach for PCNSL patients. Given the context of the high PFS, but also high TRM associated with the TBC conditioning regimen, this real-life, pilot study aimed to investigate the feasibility and efficacy of modified thiotepa-based conditioning regimens. The results highlighted that the mTBC/TT-Bu/TT-Cy protocol was well-tolerated and effective in terms of engraftment, complications, and lymphoma control. The utilization of HDC-ASCT in the initial treatment of newly diagnosed PCNSL or as salvage therapy for R/R patients who achieve a CR or PR to re-induction has been extensively investigated in several studies [ 8 , 17 , 25 – 27 ]. Given the involvement of the central nervous system (CNS) in PCNSL, there are stringent requirements for the conditioning regimen. This regimen must not only overcome the intrinsic chemoresistance of lymphoma cells but also enhance disease control by achieving elevated CNS drug concentrations, thereby circumventing chemoresistance mediated by the BBB. Thiotepa, renowned for its 100% CNS penetrance, has emerged as a crucial agent in this context. Consequently, thiotepa-based conditioning regimens, such as TBC, have been developed, demonstrating significant improvements in patient outcomes [ 17 ]. Numerous retrospective and prospective studies have examined ASCT in PCNSL using thiotepa-based conditioning regimens [ 17 , 19 , 21 , 23 , 26 – 34 ] (Table 5 ). Although the majority of these series are relatively small and encompass diverse patient populations, reported survival rates ranges from 51.4–100% at 1 to 5 years. The most extensive observational cohort study to date, drawing from registry data from the Center for International Blood and Marrow Transplant Research and including 538 adult with PCNSL patients who underwent thiotepa-based ASCT (TBC, n = 263; TT-BCNU, n = 275), indicated that those who received TBC experienced significantly lower rates of relapse (11% vs. 15%) and disease-related death (7.6% vs. 12%), higher rates of TRM (14% vs. 9%), and similar 3-year OS rates (81% vs. 78%) compared to the TT-BCNU cohort [ 27 ]. Another substantial study involving 230 PCNSL patients, evaluating therapeutic outcomes within the French Network, demonstrated superior outcomes with TBC and TT-Bu compared to TT-BCNU in terms of relapse risk and PFS with no difference in OS, but a higher TRM for TBC. The risk of TRM and deaths related to progressive disease were 46% and 39% for TBC, 33% and 33% for TT-Bu, and 8% and 79% for TT-BCNU [ 17 ]. The 5-year relapse rates were 9%, 19%, and 34% in TT-Bu, TBC, and TT-BCNU groups, respectively (P = 0.0002), and the PFS in the TBC + TT-Bu group was significantly longer than that in the TT-BCNU group. However, there was not significantly different in OS and PFS among the three groups compared with each other [ 17 ]. On the other hand, the TBC regimen demonstrated numerically superior OS and PFS rates in a systematic review of 43 studies [ 25 ]. The rates of OS after 1, 2, 3, and 5 years were 95%, 90%, 87%, and 81% in the TBC setting; 91%, 75%, 77%, and 70% in the TT-BCNU setting; and 83%, 82%, 83%, and 72% in the TT-Bu setting, respectively. Meanwhile, the PFS rates were 88%, 86%, 82%, and 81% in the TBC group; 73%, 64%, 60%, and 46% in the TT-BCNU group; and 78%, 67%, 56%, and 56% in the TT-Bu group [ 25 ]. Another systematic review analyzed 13 prospective studies including 348 patients with PCNSL who underwent first-line ASCT [ 35 ]. The pooled relapse rate of four studies [ 20 , 34 , 36 , 37 ] on 111 patients with the TBC regimen was 4%, and that was 28% for six studies [ 22 , 23 , 29 , 30 , 38 , 39 ] on 195 patients with thiotepa combined with other drugs. Results from a prospective multicenter trial by the German Cooperative PCNSL study group of 32 R/R PCNSL patients with TT-BCNU-ASCT revealed that 2-year PFS and 5-year OS rates were 56.1% and 55.6%, respectively. Notably, 3 (12.5%) patients experienced transplantation-related deaths after ASCT, including 2 patients with fatal sepsis and one case of treatment-associated CNS toxicity. Additionally, 14 (43.8%) cases resulted in death due to disease progression [ 26 ]. In a large multicenter retrospective analysis of ASCT with TBC in 79 R/R PCNSL patients, the 2- and 5-year event free survival (EFS) and DFS were 37.8% and 49.5%, respectively. Besides, there were 6 patients who died due to treatment-related toxicity after ASCT, 2 of whom were septic [ 32 ]. A prospective, single-center phase-2 study on 26 patients with TBC-ASCT revealed that 2-, 3, and 5-year PFS and OS rates were all 81%, and 3 patients died of transplant-related complications, including acute Stevens-Johnson syndrome, septic shock, and fatal chronic colitis of undetermined etiology, potentially representing graft-versus-host disease [ 20 ]. A retrospective analysis of 46 patients with PCNSL in CR1 who underwent transplantation using a TBC-based conditioning regimen indicated that the estimated of 2-year OS and PFS rates were 95% and 92%, respectively, while the 2-year TRM rate was 2.9% [ 19 ]. Results from the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS study of 44 patients with PCNSL who underwent TBC-ASCT as a first-line treatment indicated that the 2-year EFS was 87%, and the 2- and 4-year OS were both 66% [ 34 ], and the long-term results of this study revealed that the 8-year EFS and OS were 67% and 69%, respectively [ 40 ]. Moreover, 5 patients died as a result of TRM at 15, 16, 45, 169, and 220 days after ASCT, of whom 4 deaths (80%) caused by infectious complications [ 34 , 40 ]. Cote G. et al demanstrated that 37.5% (6/16) of patients with PCNSL had a documented infection during their ASCT course with TBC [ 18 ]. Montemurro M. et al. reported 5 (5/16, 31.3%) cases of infectious complications and during TT-Bu-ASCT, with 2 patients dying of septic causes at 6 and 36 days after ASCT. Table 5 Comparison with other thiotepa-based conditioning regimens for ASCT recipients with PCNSL Reference No. ASCT ASCT setting line Regimen Neutrophils recovery Platelets recovery ≥Grade III non-haematological toxicity (top, %) TRM DRM OS PFS/EFS/DFS Illerhaus et al. (2006) 23 23 First TT-BCNU a / / FN, 52.2% 0% 5y: 8.7% 5y: 87% / Kasenda B. et al. (2012) 28 34 First TT-BCNU / / / 0% / 2y: 80% / Ferreri AJM, et al. (2017) 22 58 First TT-BCNU / / FN or infection, 29.3% 3.4% / 2y: 77% 2y: 75% Kasenda B. et al. (2017) 26 32 Salvage Rituximab + TT-BCNU / / Infection, 65.6% 12.5% 43.8% 5y: 55.6% 2y: 56.1% c Schorb E, et al. (2017) 41 52 First, 15 Salvage, 37 TT-BCNU 10 / / 3.8% 25% 2y: 70.8% 2y: 62% c Montemurro M. et al. (2007) 29 16 First TT-Bu 8 11 Infection, 31.3% 31.3% 6.3% 2y: 61% 2y: 48% d Sanders S. et al. (2019) 21 30 First TT-Bu 0% / 3y: 92.7% 3y: 88.9% c Schorb E, et al. (2020) 30 13 First TT-Bu / / Infection, 7.7% 0% 7.7% 2y: 92.3% 2y: 92.9% c Soussain C. et al. (2008) 31 27 First, 15 Salvage, 12 TBC 11 18 neurologic toxicity, 18.5% 0% / / / Cote G. et al. (2012) 18 16 First TBC 9 b 13 b Mucositis, 81% 3% b / 1y: 93% b 1y: 90% c,b Soussain C. et al. (2012) 32 79 Salvage TBC / / Infection, 2.5% 7.6% 29.1% 5y: 51.4% 5y: 37.8% d , 49.5% e Welch MR. et al. (2015) 33 7 Salvage TBC 9 b 14 b FN, 33.3% 0% 0% 3y: 100% 3y: 100% c Omuro A. et al. (2015) 20 26 First TBC 9 15 FN, 42% 7.8% 3.8% 2y: 81% 2y: 81% c DeFilipp Z. et al. (2017) 19 46 First TBC 9 12 Mucositis, 35% 2.9% / 2y: 95% 2y: 92% c Houillier C. et al. (2019) 34 38 First TBC 10 18 FN, 100% 11.3% 13.2% 2y: 66% 2y: 87% d Scordo, M. et al. (2021) 27 538 First TBC, 263 TT-BCNU, 275 9 10 17 16 / 14% 9% 7.6% 12% 3y: 81% 3y: 78% 3y: 75% c 3y: 76% c Schenone L, et al. (2022) 17 230 First,119 Salvage, 111 TBC, 142 TT-Bu, 24 TT-BCNU, 64 9 # 5 # FN, 98% f 46% 33% 8% 39% 33% 79% 5y: ~ 70% 5y: ~ 88% 5y: ~ 54% 5y: ~ 64% c 5y: ~ 82% c 5y: ~ 57% c a WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation b includes total of PCNSL and SCNSL c PFS d EFS e DFS f includes total of thiotepa-based patients ASCT , autologous stem cell transplantation; PCNSL , primary central nervous system lymphoma; TRM , transplantation-related mortality; DRM , disease-related mortality; OS , overall survival; PFS , progression free survival; EFS , event free survival; DFS , disease free survival; TT-BCNU , thiotepa, carmustine; FN , febrile neutropenia; TT-Bu , thiotepa, busulfan; TBC , thiotepa, busulfan, cyclophosphamide Although preliminary studies on thiotepa-based ASCT have been conducted on small and heterogeneous patients cohorts, making interpretation challenging, these findings stronglysuggest a potential benefit for TBC-ASCT in PCNSL. However, the TRM, particularly caused by serious infections, warrants attention, and the optimal conditioning regimen remains elusive. Collectively, these studies indicated that the benefit to risk ratio of TBC-ASCT could be improved through dose adjustments to the conditioning regimen. In the present study, patients received a mTBC regimen, where the cyclophosphamide dosage was reduced to 1 g/m 2 /d for two days compared with the traditional TBC regimen of 60 mg/kg/d for two days. For fragile patients, the decision to use TT-Bu was made by the physician, while TT-Cy was utilized for ASCT incorporated with CAR-T therapy (Tables 1 and 3 ). With a median follow-up time of 4.5 (range, 1.9–34.7) months, all patients achieved CR at the first assessment after ASCT, with only one patient experiencing disease progression at 6 months post-ASCT. All patients were alive at the last follow-up. The estimated 1- and 3-year PFS rates were 80.0% and 53.3%, respectively, while both the 1- and 3-year OS rates were 100% (Table 3 and Fig. 2 ). Although 2 (16.7%) cases developed septicemia, one due to Escherichia coli and the other due to CRE, specifically KP, both patients recovered with favorable outcomes. It is noteworthy that no TRM occurred in this series. Hematopoietic reconstitution is the primary efficient and safe indicator for conditioning regimen, and early implementation of transplantation significantly reduces the risk of transplantation-related complications and deaths, particularly severe infections. Previous studies on TBC or TT-Bu-ASCT have reported median time to neutrophil and platelet recovery of 8–11 days and 11–18 days, respectively [ 18 – 20 , 29 , 31 , 33 , 34 ]. In the present study, all patients achieved sustained hematological recovery earlier than previous reports, with neutrophil recovery at a median time of 9 (7–12) days and platelet engraftment at a median time of 10 (6–12) days. The reported main grade 3/4 complications during thiotepa-based conditioning with ASCT were febrile neutropenia (29.3–100%), infection (7.7–65.6%), oral mucositis (4–81%), diarrhea (4–42%), acute delirium/neurologic toxicity (6.25–22%), cutaneous toxicity (0–24%), engraftment syndrome (0–17%), bronchial obstruction (0–13%), epileptic seizure (0–9%), cardiac arrhythmias or cardiac failure (0–8%), hemorrhagic cystitis (0–6%), SOS (0–5%), etc. [ 17 – 20 , 29 – 32 , 34 ]. A large retrospective study reported as high as 98% for febrile neutropenia (FN) and 81% for oral mucositis [ 17 ]. A randomized Phase II study indicated that FN occurred in all 44 patients, and nonhematologic and noninfectious grade 3 or higher toxicities included alopecia (100%) and oral or gastrointestinal mucositis (77%) [ 34 ]. Cote G. et al reported that 31.3% (6/16) of patients had a documented infection during their ASCT course with TBC, and 81% (13/16) had grade 3 and 4 mucositis [ 18 ]. In another prospective study, the most common grade 3 or higher toxicities were FN (11/26, 42%), infection (7/26, 26.9%), and skin rash (3/26, 11.5%) [ 20 ]. DeFilipp Z et al.’s research indicated that the most common toxicities were infections (18/46, 39.1%) and severe mucositis (16/46, 35%), with a higher rate of engraftment syndrome (8/46, 17%) [ 19 ]. In the present study, the types of common complications were consistent with previous reports but with much lower incidences, especially in infection (16.7%), diarrhea (50%), and oral mucositis (16.7%). Notably, the incidence of transient acute delirium (25%) with a favorable outcome appeared to be relatively high. It is noteworthy that none of these toxicities led no TRM. In the present study, the outcomes confirmed the encouraging tolerance and safety of the mTBC/TT-Bu/TT-Cy-ASCT protocol. However, longer-term follow-up is essential to definitively assess survival benefits. Two long-term randomized trial results of PCNSL patients treated with TBC/TT-BCNU followed by ASCT have indicated that ASCT appears to be highly effective in preventing relapses and improving functions and quality of life. The estimated 8-year EFS and OS rates were reported as 67% and 69% [ 40 ], and the 7-year OS was 70% [ 41 ], confirming that present study will likely yield promising long-term survival results. In addition to continued patient follow-up, prospective clinical trials will be conducted to accurately assess patients who would benefit from either the mTBC or TT-Bu regimens. The optimal timing for ASCT is clear, in which undergoing ASCT in the first-line setting is superior to the salvage setting [ 17 , 31 , 42 ] (Table 5 ). The report of French Network revealed that the 5-year OS of ASCT in the first-line treatment and at first-relapse PCNSL was 80% and 50%, respectively [ 17 ]. Another retrospective international study suggested that the 2-year PFS and OS rates were both 80% for patients undergoing ASCT as first-line treatment, and those were 54.0% and 65.6% for patients undergoing ASCT as second or subsequent line of treatment, respectively [ 42 ]. A prospective phase II multicenter study showed that the 2-year OS and 2-year PFS rates was 69% and 58% after TBC-HSCT as the first-line and salvage treatment for PCNSL patients, respectively [ 31 ]. A systematic review of 43 studies on ASCT indicated that the OS rates were 94%, 86%, 82%, and 70% at 1, 2, 3, and 5 years in the consolidation setting, and 75%, 63%, 56%, and 54% at the same intervals in the salvage/relapse settings. Additionally, the overall risk of relapse at 5 years was 24% in the consolidation setting and 29% in the salvage/relapse settings. Besides, the pooled TRM rates were 1% and 4% in patients who underwent ASCT in the consolidation and salvage/ relapse settings [ 25 ]. These results indicated that patients who had chemosensitive disease and received early HDC-ASCT as first-line consolidation treatment exhibited a better prognosis, as well as superior survival. The main changes in the latest European Association of Neuro-Oncology (EANO) guidelines for treatment of PCNSL versus previous guideline include strengthened evidence for the consolidation with ASCT in the first-line treatment [ 43 ]. In the present study, half of the patients received ASCT as the fist-line consolidation and salvage treatment, respectively. All patients except one, who declined maintenance therapy due to financial reasons, experienced relapse at + 181d post-ASCT, while they returned to sustained CR. Due to the limited number of cases, relatively short-term follow-up, and all patients being alive, no survival comparison was conducted. Because PCNSL is a special subtype of DLBCL, the prognosis of PCNSL is significantly worse than that of systemic DLBCL with a high rate of recurrence, particularly in the first 2 years after treatment [ 44 ]. Furthermore, when recurrence occurs, it mainly results in a devastating and irreversible impact on neurologic function. Therefore, maintenance therapy, immune cell therapy, and the utilization of targeted agents based on the molecular and biological properties of the disease may promote precision medicine, potentially leading to long-term disease-free survival and even cure [ 44 – 47 ]. However, the questions of whether, when, and which maintenance therapies provide benefit for PCNSL patients remain to be addressed [ 10 ]. Tsang M. et al. performed a narrative review on the rationale for maintenance strategies in PCNSL patients, and indicated that the overall role of maintenance therapy may potentially improve survival and preserve quality of life and function in a vulnerable, older patient population [ 48 ]. Baireya S. et al. evaluated the possible role of maintenance treatment for PCNSL patients, and they pointed out that high-risk and elderly patients, who often experience a high relapse rate, short PFS, and OS, should be considered for maintenance treatment [ 46 ]. In the present study, upon physician recommendation, all patients except one received maintenance therapy, with 9 patients starting within 3 months after ASCT. All patients who underwent maintenance therapy were in CR, and the longest duration of maintenance exceeded 2 years, indicating the effectiveness and reasonable tolerability of post-ASCT maintenance. The drugs used for maintenance included MTX, rituximab, lenalidomide, procarbazine, temozolomide, programmed cell death-1 (PD-1) inhibitors, thiotepa, and BTKi [ 49 – 58 ]. In the present study, the majority of patients received BTKi for maintenance therapy because of its excellent performance in PCNSL as reported previously [ 59 – 63 ]. A small scale study suggested that anti-CD19 CAR-T cell therapy appeared feasible for patients with R/R PCNSL [ 64 ]. A phase I/II clinical trial and some case reports demonstrated the safety and efficacy of CAR-T cells with some durable responses [ 56 , 65 – 67 ]. Moreover, several trials indicated that combining CAR-T cell administration with ASCT was safe and efficacious, and its long-term efficacy was further improved in patients with B-cell NHL, including PCNSL [ 68 – 72 ]. In the present study, there were 3 R/R PCNSL patients who received CAR-T cell therapy, including one who received infusion of CAR-T cells on + 3d post-ASCT, and one who underwent individual CAR-T therapy as consolidation on + 49d post-ASCT, and one who received CAR-T therapy for late relapse on + 554d post-HSCT. All of these three patients achieved sustained CR. This small-scale, real-life study indicated the safety and feasibility of different clinical application scenarios of CAR-T and HDC-ASCT for PCNSL, while the optimal combined application needs to further investigation. The present study has notable limitations, including the small sample size and relatively short follow-up. However, it is noteworthy that patients in this study were enrolled consecutively and underwent a consistent protocol for HDC-ASCT, ensuring the reliability of the conclusions drawn. This study presented real-life outcomes of PCNSL patients treated with a modified thiotepa-based conditioning regimen followed by ASCT. The findings provided valuable insights. Firstly, the modified thiotepa-based conditioning regimen and ASCT should be considered as intensified first-line consolidation therapy for PCNSL. Secondly, optimal patient selection criteria for mTBC or TT-Bu regimens need to be carefully stratified. Lastly, the utilization of TT-Cy for ASCT combined with CAR-T therapy should be further investigation in a larger patient cohort. Long-term survival outcomes will require validation in the future larger-scale follow-up research. In conclusion, this study assessed the modified thiotepa-based conditioning regimens and confirmed their safety and efficacy in ASCT for PCNSL patients. It made a significant contribution to the utilization of HDC-ASCT for PCNSL, supporting the ongoing interest in thiotepa-based conditioning regimens. Additionally, this study highlighted the trend towards integrated, multi-measure management of PCNSL. Declarations Author contribution Hongmei J was responsible for the conception and design of the study; Yan L and Hongmei J designed the study. Yan L, Sen L, and Fang B collected and interpreted the data. Yan L analyzed the data and drafted the manuscript. Lan M, Wei Z, and Ping Y provided study patients and valuable advice; Fei D and JiJun W supervised the clinical protocol and provided the expert consultations. Yan L and Hongmei J revised the manuscript. All authors have read and approved the final manuscript. Funding This work was supported by the special fund of the National Clinical Key Specialty Construction Program, P.R. China (2023), Beijing Municipal Natural Science Foundation (7232202), Beijing Bethune Charitable Foundation (J202201E023), Key Clinical Projects of Peking University Third Hospital (No.BYSYDL2021006). Acknowledgments The authors thank the patients and their families who contributed to this study. The authors would also like to acknowledge the doctors and nurses in our department for taking care of these patients. Data accessibility The data that support the findings of this study are available from the corresponding author upon reasonable request. Conflict of Interest The authors declare they have no potential conflict of interests. Ethics Statement This study was approved by The Ethics Committee of Peking University Third Hospital，and signed informed consents were obtained from all patients in accordance with principles of Declaration of Helsinki. 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The journal of medical investigation 68(3.4):286-91. https://doi.org/10.2152/jmi.68.286 Hoang-Xuan K, Taillandier L, Chinot O et al (2003) Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Journal of clinical oncology 21(14):2726-31. https://doi.org/10.1200/JCO.2003.11.036 Ambady P, Fu R, Szidonya L, Peereboom DM, Doolittle ND, Neuwelt EA (2020) Impact of maintenance rituximab on duration of response in primary central nervous system lymphoma. Journal of neuro-oncology 147(1):171-6. https://doi.org/10.1007/s11060-020-03411-0 Fritsch K, Kasenda B, Schorb E et al (2017) High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia 31(4):846-52. https://doi.org/10.1038/leu.2016.334 Pulczynski EJ, Kuittinen O, Erlanson M et al (2015) Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica 100(4):534-40. https://doi.org/10.3324/haematol.2014.108472 Vu K, Mannis G, Hwang J, Geng H, Rubenstein JL (2019) Low-dose lenalidomide maintenance after induction therapy in older patients with primary central nervous system lymphoma. British journal of haematology 186(1):180-3. https://doi.org/10.1111/bjh.15787 Faivre G, Butler MJ, Le I, Brenner A (2019) Temozolomide as a Single Agent Maintenance Therapy in Elderly Patients With Primary CNS Lymphoma. Clinical lymphoma, myeloma & leukemia 19(10):665-9. https://doi.org/10.1016/j.clml.2019.05.012 Zou R, Zhou X, Liu H, Wang P, Xia F, Kang L, Yu L, Wu D, Jin Z, Qu C (2023) Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient. Cancer research and treatment 55(4):1363-8. https://doi.org/10.4143/crt.2023.371 Wang L, Fan Y, Chen et al (2023) Case report: Successful treatment of a patient with relapsed/refractory primary central nervous system lymphoma with thiotepa-based induction, autologous stem cell transplantation and maintenance. Frontiers in oncology 13:1333761. https://doi.org/10.3389/fonc.2023.1333761 Grommes C, Pastore A, Palaskas N et al (2017) Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer discovery 7(9):1018-29. https://doi.org/10.1158/2159-8290.CD-17-0613 Shen J, Liu J (2022) Bruton's tyrosine kinase inhibitors in the treatment of primary central nervous system lymphoma: A mini-review. Frontiers in oncology 12:1034668. https://doi.org/10.3389/fonc.2022.1034668 Yang C, Cui Y, Ren X et al (2022) Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series. Frontiers in oncology 12:901797. https://doi.org/10.3389/fonc.2022.901797 Song J, Liu H, Shen HL et al (2021) Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma. Zhonghua xue ye xue za zhi 42(11):917-22. https://doi.org/10.3760/cma.j.issn.0253-2727.2021.11.006. Liu Y, Sun J, Tuo K (2023) Zanubrutinib in the Maintenance Treatment of Elderly People with Primary Central Nervous System Lymphoma: A Report of 2 Cases. Case reports in oncology 16(1):227-33. https://doi.org/10.1159/000529315 Bairey O, Taliansky A, Glik A et al (2023) A phase 2 study of ibrutinib maintenance following first-line high-dose methotrexate-based chemotherapy for elderly patients with primary central nervous system lymphoma. Cancer 129(24):3905-14. https://doi.org/10.1002/cncr.34985 Miyao K, Yokota H, Sakemura RL (2022) Is CD19-directed chimeric antigen receptor T cell therapy a smart strategy to combat central nervous system lymphoma? Frontiers in oncology 12:1082235. https://doi.org/10.3389/fonc.2022.1082235 Frigault MJ, Dietrich J, Gallagher K et al (2022) Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial. Blood 139(15):2306-15. https://doi.org/10.1182/blood.2021014738 Alcantara M, Houillier C, Blonski M et al (2022) CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network. Blood 139(5):792-6. https://doi.org/10.1182/blood.2021012932 Tu S, Zhou X, Guo Z et al (2019) CD19 and CD70 Dual-Target Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Relapsed and Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma. Frontiers in oncology 9:1350. https://doi.org/10.3389/fonc.2019.01350 Sauter CS, Senechal B, Riviere I et al (2019) CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Blood 134(7):626-35. https://doi.org/10.1182/blood.2018883421 Wang X, Popplewell LL, Wagner JR et al (2016) Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood 127(24):2980-90. https://doi.org/10.1182/blood-2015-12-686725 Wei J, Xiao M, Mao Z et al (2022) Outcome of aggressive B-cell lymphoma with TP53 alterations administered with CAR T-cell cocktail alone or in combination with ASCT. Signal transduction and targeted therapy 7(1):101. https://doi.org/10.1038/s41392-022-00924-0 Cao Y, Xiao Y, Wang N, Wang G et al (2021) CD19/CD22 Chimeric Antigen Receptor T Cell Cocktail Therapy following Autologous Transplantation in Patients with Relapsed/Refractory Aggressive B Cell Lymphomas. Transplantation and cellular therapy 27(11):e910-1. https://doi.org/10.1016/j.jtct.2021.08.012 Wu J, Meng F, Cao Y, Zhang Y, Zhu X, Wang N, Wang J, Huang L, Zhou J, Xiao Y (2021) Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma. Blood cancer journal 11(7):131. https://doi.org/10.1038/s41408-021-00523-2 Additional Declarations No competing interests reported. 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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-4403718","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":305287362,"identity":"ae54b720-cbd7-41b7-b180-212747cd10f0","order_by":0,"name":"Yan Li","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Li","suffix":""},{"id":305287363,"identity":"f063e560-cd2e-4e54-be1d-7b79149f25ae","order_by":1,"name":"Sen Li","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sen","middleName":"","lastName":"Li","suffix":""},{"id":305287364,"identity":"052ede6a-eab8-4a6c-8c7c-c68f54b8e66c","order_by":2,"name":"Fang Bao","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Bao","suffix":""},{"id":305287365,"identity":"f49db907-7450-4d1e-aae7-a269c5ec713b","order_by":3,"name":"Lan Ma","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lan","middleName":"","lastName":"Ma","suffix":""},{"id":305287366,"identity":"af9d2502-634b-4cfa-a98a-03658ed2d18b","order_by":4,"name":"Wei Zhao","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Zhao","suffix":""},{"id":305287367,"identity":"da66768c-2537-4f56-b14a-aaa18e867924","order_by":5,"name":"Ping Yang","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Yang","suffix":""},{"id":305287369,"identity":"db1e9738-2e05-49d7-8d9d-13842d639342","order_by":6,"name":"Fei Dong","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Dong","suffix":""},{"id":305287371,"identity":"bf7c8e2f-4cd4-4f6f-9bee-6ca1dff54a61","order_by":7,"name":"Jijun Wang","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jijun","middleName":"","lastName":"Wang","suffix":""},{"id":305287372,"identity":"07d17633-95e3-4606-95aa-c154f293c14e","order_by":8,"name":"Hongmei Jing","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBACAwglwczGwMD4mIEHWZAILczGpGgBAzZpLIKYwJy99/CrGxUW7HzS7deqC2S2JTawN2+TYKi5g1OLZc+5NOucM0CHyZwpuz2D53ZiA8+xMgmGY89wO+xGjplxbhtQi0RO2m0ekBaJHDMJxobDBLT8g2gpBmuRf0NQi/Hj3AaQlvRjzBBbeAhoOXPGjDnnGNgWZmmgX4zbeNKKLRKO4dFyvMf4c05NXbL8jPSHnwt7bsv2sx/eeONDDW4tQMAmASSSGRh4DBgYe4BckFgCPg3ASP8AJOwYGNgfMDD8wK90FIyCUTAKRiYAAAV4T2LkocuqAAAAAElFTkSuQmCC","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hongmei","middleName":"","lastName":"Jing","suffix":""}],"badges":[],"createdAt":"2024-05-11 06:08:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4403718/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4403718/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57509234,"identity":"c4b10094-94d8-4f2a-8e3f-cac772220c94","added_by":"auto","created_at":"2024-05-31 16:14:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":17852,"visible":true,"origin":"","legend":"\u003cp\u003eSwimming plots of response and survival of PCNSL patients with HDC-ASCT. PCNSL, primary central nervous system lymphoma; HDC-ASCT, high dose chemotherapy followed by autologous stem cell transplantation; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; WBRT, whole-brain radiotherapy; CAR-T, chimeric antigen receptor T-cell.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4403718/v1/354f5b38e1c93c18f3a2f56d.png"},{"id":57509235,"identity":"5052ebc1-d29a-4648-8806-404df62c32ce","added_by":"auto","created_at":"2024-05-31 16:14:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":8518,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival of PCNSL patients after HDC-ASCT (A \u0026amp; B). PCNSL, primary central nervous system lymphoma; HDC-ASCT, high dose chemotherapy followed by autologous stem cell transplantation\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4403718/v1/7d419372ca8f822aa3dbc06b.png"},{"id":57898741,"identity":"7945ced3-1487-4f42-8ff4-31f925bf801c","added_by":"auto","created_at":"2024-06-07 08:20:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1150605,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4403718/v1/39bce777-201c-4e74-bf50-7cf6e2ffdc7a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The notable outcomes of modified thiotepa-based conditioning followed by autologous stem cell transplantation in primary central nervous system lymphomas: A real-life pilot study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary central nervous system lymphoma (PCNSL) is an aggressive, heterogeneous, and rare neoplasm of extra-nodal non-Hodgkin lymphoma (NHL), developing in the brain, spinal cord, cranial nerves, leptomeninges and vitreo-retina [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. PCNSL is mainly diffuse large B-cell lymphomas (DLBCLs) of the activated B-cell (ABC) subtype, associating with a poor prognosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Several clinical trials have demonstrated the benefit of high-dose chemotherapy (HDC) for PCNSL patients, followed by HDC-autologous stem cell transplantation (HDC-ASCT) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Several clinical consensus/guidelines recommend HDC-ASCT as consolidation therapy for younger patients (up to age 65\u0026ndash;70) with newly-diagnosed PCNSL, or as salvage treatment for relapsed/refractory PCNSL [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. According to the efficient penetration of the blood-brain barrier (BBB), high-dose thiotepa-based conditioning chemotherapy has been proposed for PCNSL [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], while the carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen widely used in systemic lymphomas was confirmed with suboptimal disease control for PCNSL [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, there are still gaps in knowledge and unmet needs regarding the lack of consensus on the appropriate thiotepa-based regimens. The thiotepa, busulfan, and cyclophosphamide (TBC) conditioning regimen exhibited higher rates of progression-free survival (PFS) and transplantation- related mortality (TRM) compared with thiotepa and carmustine (TT-BCNU). This counteracted the potential benefit of PFS leading to no overall survival (OS) advantage [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, dose adjustment of the conditioning regimen is essential. The present study, aimed to optimize this strategy utilizing the reduced intensity, modified thiotepa-based conditioning regimen for PCNSL patients receiving ASCT to improve the tolerance and efficacy of ASCT.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThis retrospective, real-life pilot study involved a total of 12 patients with PCNSL who received ASCT based on modified thiotepa-based conditioning regimens in our center between March 2021 and December 2023. All patients survived and were followed up until January 31, 2024, with a median follow-up time of 135 days (range, 57\u0026ndash;1014) following transplantation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eConditioning regimen and ASCT\u003c/h2\u003e \u003cp\u003eThe commonly used TBC regimens consisted of intravenous thiotepa (250 mg/m\u003csup\u003e2\u003c/sup\u003e/d, D-9 through D-7), busulfan (3.2 mg/kg/d, D-6 through D-4), and cyclophosphamide (60 mg/kg/d, D-3, D-2), followed by ASCT on D0. The reduced intensity chemotherapy included TT-Bu (thiotepa, 300 mg/m\u003csup\u003e2\u003c/sup\u003e/d, D-6, D-5, busulfan, 3.2 mg/kg/d, D-4 through D-2, and TT-BCNU (thiotepa, 400 mg/m\u003csup\u003e2\u003c/sup\u003e/d, D-6, carmustine, 5 mg/kg/d, D-5, D-4), as described previously [\u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In this study, the modified thiotepa-based conditioning regimens, consisted of mTBC (thiotepa, 300 mg/m\u003csup\u003e2\u003c/sup\u003e/d, D-8 and D-7, busulfan, 3.2 mg/kg/d, D-6 through D-4, and cyclophosphamide, 1 g/m\u003csup\u003e2\u003c/sup\u003e/d, D-3 and D-2) with stem cell reinfusion on day 0, TT-Bu (thiotepa, 300 mg/m\u003csup\u003e2\u003c/sup\u003e/d, D-8 and D-7, busulfan, 3.2 mg/kg/d, D-6 through D-4) for ASCT in patients with fragile conditions, and TT-Cy (thiotepa, 300 mg/m\u003csup\u003e2\u003c/sup\u003e/d, D-5 and D-4, cyclophosphamide, 1 g/m\u003csup\u003e2\u003c/sup\u003e/d, D-3 and D-2) for ASCT incorporated with chimeric antigen receptor T-cell (CAR-T) therapy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Planned CD19 CAR-T therapy involved ASCT incorporated with CAR-T cell infusion on d\u0026thinsp;+\u0026thinsp;3, and individual CAR-T therapy was considered as consolidation in the early phase post-ASCT for progressive patients before ASCT. The selection of different strategies depended on the patient\u0026rsquo;s preferences and the discretion of the treating physician. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 were utilized to identify grade 3\u0026ndash;5 toxicities associated with ASCT. Supportive therapy followed institutional guidelines, including granulocyte stimulating factor, seizure and infection prophylaxis, hydration, antiemesis, and irradiated blood products.\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\u003eThiotepa-based conditioning regimens for ASCT recipients with PCNSL\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegimens\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecarmustine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ethiotepa\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ebusulfan\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecyclophosphamide\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250 mg/m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-9, -8, -7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2 mg/kg/d,\u003c/p\u003e \u003cp\u003ed-6, -5, -4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60 mg/kg/d,\u003c/p\u003e \u003cp\u003ed-3, -2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300 mg/m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-6, -5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2 mg/kg/d,\u003c/p\u003e \u003cp\u003ed-4, -3, -2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT-BCNU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e400mg/m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 mg/kg/d,\u003c/p\u003e \u003cp\u003ed-5,-4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22, 23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300 mg/m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-8, -7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2 mg/kg/d,\u003c/p\u003e \u003cp\u003ed-6, -5, -4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1g /m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-3, -2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT-Cy\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300 mg/m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-5, -4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 g/m\u003csup\u003e2\u003c/sup\u003e/d,\u003c/p\u003e \u003cp\u003ed-3, -2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003efor ASCT incorporated with chimeric antigen receptor T-cell therapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eASCT\u003c/em\u003e, autologous stem cell transplantation; \u003cem\u003ePCNSL\u003c/em\u003e, primary central nervous system lymphoma; \u003cem\u003eTBC\u003c/em\u003e, thiotepa, busulfan, cyclophosphamide; \u003cem\u003emTBC\u003c/em\u003e, modified TBC; \u003cem\u003eTT-BCNU\u003c/em\u003e, thiotepa, carmustine; \u003cem\u003eTT-Bu\u003c/em\u003e, thiotepa, busulfan; \u003cem\u003eTT-Cy\u003c/em\u003e, thiotepa, cyclophosphamide\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy evaluation and maintenance therapy\u003c/h2\u003e \u003cp\u003eBrain magnetic resonance imaging (MRI) with contrast-enhanced and diffusion-weighted imaging (DWI) employed for the diagnosis and assessment of treatment efficacy in PCNSL patients. Whole-body fluorodeoxyglucose positron emission tomography (PET) was utilized to evaluate PCNSL patients at cspecific time points, such as the time of initial diagnosis or at relapse in accordance with recommendations from consensus guidelines reported by the Chinese Neurosurgical Society of the Chinese Medical Association (CNSCMA) and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association (SHM-CACA) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Besides, response assessment was conducted before transplantation, one month after ASCT, and then every 3 months until 2 years post-transplantation. Subsequent evaluations were scheduled every 6 months until 5 years and annually thereafter. In cases where MRI indicated progression or relapse, PET imaging was recommended. Treatment response for complete response (CR), unconfirmed complete response (CRu), partial response (PR), stable disease (SD), progressive disease (PD), and relapsed disease was assessed according to the guideline of the International PCNSL Collaborative Group (IPCG) for PCNSL [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInitiation of maintenance therapy is strongly recommended within 3 months after ASCT, and the therapy should be maintained for two years in this study unless there is disease progression, or intolerable toxicity. The selection of drugs for maintenance therapy is based on the physician\u0026rsquo;s recommendations, considering the patients\u0026rsquo; prior treatment and their preferences.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe PFS was calculated as the duration from ASCT to the first time of progression, recurrence, death, or the last follow-up. The OS was defined as the time between ASCT and death from any cause or the last follow-up. TRM was defined as non-relapse-related deaths caused by transplantation occurring during and after ASCT. The time points before and after transplantation were presented by \u0026lsquo;-\u0026rsquo; or \u0026lsquo;+\u0026rsquo; signs. The demographic and clinical characteristics were summarized using descriptive statistics. Survival analysis was performed by the Kaplan\u0026ndash;Meier method. The statistical analysis was carried out by SPSS 20.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism 7.0 (GraphPad Software Inc., San Diego, CA, USA) software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and clinical characteristics\u003c/h2\u003e \u003cp\u003eData of 12 PCNSL patients who underwent ASCT with modified thiotepa-based conditioning regimens, including 5 men and 7women are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e Patients\u0026rsquo; median age at the time of ASCT was 57.5 (range, 37‒66) years, of whom 2 (16.7%) patients aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years. Moreover, 9 (75%) patients had and an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of \u0026ge;\u0026thinsp;2 points at the time of diagnosis due to PCNSL symptoms. Notably, 91.7% (11/12) of patients had brain involvement, with 8 (66.7%) patients displaying multiple lesions. Additionally, 7 patients (58.3%) showed lesions in the deep brain structures, such as the basal ganglia, corpus callosum, brain stem, and cerebellum). Biopsy results were achieved for all patients, with 11 (91.7%) identified as the ABC subtype. Among 4 patients whose tumor tissues underwent targeted-mutation testing utilizing next-generation sequencing (NGS), MYD88 was the most common mutation occurring in all cases (100%, 4/4), followed by PIM1 in 75% (3/4) of cases (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Two-thirds of the patients had an elevated lactate dehydrogenase (LDH) level (LDH\u0026thinsp;\u0026ge;\u0026thinsp;246 U/L ). However, due to the poor status of patients at diagnosis, only half of the patients underwent lumbar puncture and cerebrospinal fluid (CSF) examination. Among 6 patients with available CSF protein data, all had normal CSF protein level. Two of the remaining six patients without CSF protein data could not be evaluated using the PCNSL prognosis system established by the International Extranodal Lymphoma Study Group (IELSG). In 10 patients, 3 (30%) were categorized as low-risk, and 7 (70%) were categorized as intermediate-risk according to the IELSG score.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of HDC-ASCT recipients with PCNSL (n\u0026thinsp;=\u0026thinsp;12)\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\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;12, %\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 ASCT, years, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.5 (37, 66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at ASCT\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\u003e\u0026lt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\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\u003e5 (41.7)\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\u003e7 (58.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG-PS at diagnosis\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\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (75.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSites involved at diagnosis\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\u003eBrian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (91.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsolated CSF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsolated intraocular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLesions at diagnosis\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\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvolvement of deep brain structure\u003csup\u003ea\u003c/sup\u003e\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\u003e7 (58.3)\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\u003e5 (41.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH\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\u003eElevated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \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\u003e8 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF protein\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\u003eElevated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \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\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology\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\u003eDLBCL-ABC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (91.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLBCL-GCB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIELSG scoring system\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow risk (0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (30.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntermediate risk (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (70.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh risk (4\u0026ndash;5 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior treatment line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOne prior line\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwo prior lines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than two prior lines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemission status at ASCT\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\u003eCR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (41.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;CR2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASCT strategy\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\u003eIn first-line consolidative treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalvage treatment at relapse/refractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from diagnosis to ASCT, month, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.2 (5.2-102.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (41.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConditioning regimen\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\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (58.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT-Cy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGraft\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\u003eMNCs, \u0026times;10\u003csup\u003e8\u003c/sup\u003e/kg, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.57 (3.06\u0026ndash;7.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD34+, \u0026times;10\u003csup\u003e6\u003c/sup\u003e/kg, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.83 (1.1\u0026ndash;9.51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEngraftment, days post ASCT\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\u003eANC, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (6\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003ea\u003c/sup\u003eInvolvement of deep structures of the brain, ie, basal ganglia and/or corpus callosum and/or brain stem and/or cerebellum\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003eb\u003c/sup\u003eTwo patients without CSF protein data could not be evaluated\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eHDC-ASCT\u003c/em\u003e, high dose chemotherapy (HDC) followed by autologous stem cell transplantation; \u003cem\u003ePCNSL\u003c/em\u003e, primary central nervous system lymphoma; \u003cem\u003eECOG-PS\u003c/em\u003e, Eastern Cooperative Oncology Group Performance Status; \u003cem\u003eCSF\u003c/em\u003e, cerebrospinal fluid; \u003cem\u003eLDH\u003c/em\u003e, lactate dehydrogenase; \u003cem\u003eDLBCL\u003c/em\u003e, diffuse large B-cell lymphoma; \u003cem\u003eABC\u003c/em\u003e, activated B cell; \u003cem\u003eGCB\u003c/em\u003e, germinal center B; \u003cem\u003eIELSG\u003c/em\u003e, International Extranodal Lymphoma Study Group; \u003cem\u003eCR\u003c/em\u003e, complete response; \u003cem\u003ePR\u003c/em\u003e, partial response; \u003cem\u003ePD\u003c/em\u003e, progressive disease; \u003cem\u003emTBC\u003c/em\u003e, modified thiotepa, busulfan, cyclophosphamide; \u003cem\u003eTT-Bu\u003c/em\u003e, thiotepa, busulfan; \u003cem\u003eTT-Cy\u003c/em\u003e, thiotepa, cyclophosphamide; \u003cem\u003eMNCs\u003c/em\u003e, mononuclear cells; \u003cem\u003eANC\u003c/em\u003e, absolute neutrophil count; \u003cem\u003ePLT\u003c/em\u003e, platelet\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eChemotherapy and outcomes before ASCT\u003c/h2\u003e \u003cp\u003eIt was found that 6 patients received two or more lines chemotherapy pre-ASCT, of whom one patient received whole-brain radiotherapy (WBRT) due to disease progression. The median time from diagnosis to initial treatment was 24.5 (range, 1‒50) days. Patients\u0026rsquo; detailed clinical data are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. For first-line therapy, only one patient with isolated intraocular disease received a regimen of local methotrexate (MTX) combined with rituximab and lenalidomide (RL) regimen. High-dose-MTX (HD-MTX) based chemotherapy, ranging from 3.0 to 3.5 g/m\u003csup\u003e2\u003c/sup\u003e was the mainstay for the majority of patients (91.7%). The Bruton\u0026rsquo;s tyrosine kinase inhibitor (BTKi) was incorporated into the first-line therapy for 45.4% (5/11) of patients, and into second-line therapy for 66.7% (4/6) of patients with relapsed or refractory PCNSL (R/R PCNSL). Prior to transplantation, five patients achieved sustained CR, and one patient achieved PR. Forthermore, five patients experienced relapse but achieved CR with multi-course re-induction chemotherapy, while two patients had progressive disease until undergoing ASCT. The median number of total courses before ASCT was 7.5 (range, 6‒23) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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\u003eIndividual patient characteristics, previous treatments and outcome after transplantation (n\u0026thinsp;=\u0026thinsp;12, FU to Jan. 31st, 2024)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"16\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender/age at HSCT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInitial disease site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTissue gene mutations by NGS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInitial treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDuration of first response, mo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo. of relapse\u003c/p\u003e \u003cp\u003epre-HSCT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRe-induction regimen and treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTotal courses pre-HSCT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eRemission status at HSCT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eTime from diagnosis to HSCT, mo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eConditioning\u003c/p\u003e \u003cp\u003eregimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eMaintenance treatment post-HSCT, drug, duration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePFS from HSCT\u003c/p\u003e \u003cp\u003emo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eOS status and duration from HSCT\u003c/p\u003e \u003cp\u003emo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003eRemission status at last follow-up\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\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRight eye\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLocal MTX, RL,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRL-MTX, E, Z, MA, R-Z\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;E\u0026thinsp;+\u0026thinsp;Docorubicin\u0026thinsp;+\u0026thinsp;P\u003csup\u003eb\u003c/sup\u003e, MA\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eZanubrutinib,\u003c/p\u003e \u003cp\u003e8 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MA, R-MA\u0026thinsp;+\u0026thinsp;TMZ, L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMTX\u0026thinsp;+\u0026thinsp;L\u0026thinsp;+\u0026thinsp;TMZ, RL-TMZ, R-CHOPE\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eTT-Bu\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eTislelizumab, 12 mo.\u003c/p\u003e \u003cp\u003eOrelabrutinib,\u003c/p\u003e \u003cp\u003e8 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MTX\u0026thinsp;+\u0026thinsp;TMZ, R-COPADM1\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MA, R-MTX\u0026thinsp;+\u0026thinsp;Ibrutinib, R-COPADM\u0026thinsp;+\u0026thinsp;Ore\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib\u0026thinsp;+\u0026thinsp;lenalidomide, 24 mo., continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eMYD88\u003c/em\u003e,\u003cem\u003ePIM1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MTX\u0026thinsp;+\u0026thinsp;TMZ, R-MA\u003csup\u003eb\u003c/sup\u003e, MATRix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib, 2 mo. continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MAD, EA\u003csup\u003e,\u003c/sup\u003e,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOre-MTDEA, modified TEDDi-R\u003csup\u003eb\u003c/sup\u003e, Ore-MTX\u0026thinsp;+\u0026thinsp;TMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eTT-Bu\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib\u0026thinsp;+\u0026thinsp;lenalidomide, 3 mo., continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MTX\u0026thinsp;+\u0026thinsp;TMZ\u0026thinsp;+\u0026thinsp;vincristine\u0026thinsp;+\u0026thinsp;teniposide, MA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003emotdfied TEDDi-R\u003csup\u003eb\u003c/sup\u003e, R-MA, RL-Ore\u0026thinsp;+\u0026thinsp;Pemetrexed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19 CAR-T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eMYD88\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOre, R\u0026thinsp;+\u0026thinsp;MTX\u0026thinsp;+\u0026thinsp;TMZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eRefractory disease,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMATRix, modified TEDDi-R\u003csup\u003eb\u003c/sup\u003e, WBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eTT-Cy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib, 1 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-Z\u0026thinsp;+\u0026thinsp;MTX, modified TEDDi-R\u003csup\u003eb\u003c/sup\u003e, MATRix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eZanubrutinib, 8 days, continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eBCL2\u003c/em\u003e, \u003cem\u003eMYD88\u003c/em\u003e、\u003cem\u003eIRF4\u003c/em\u003e, \u003cem\u003ePIM1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MTX\u0026thinsp;+\u0026thinsp;vincristine, R-MTX\u0026thinsp;+\u0026thinsp;Ore, R-TMZ\u0026thinsp;+\u0026thinsp;Ore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003emTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib, 5 days, continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MTX, R- thiotepa\u0026thinsp;+\u0026thinsp;Ore, R-MA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTEDDi-R\u0026thinsp;+\u0026thinsp;selinexor\u003csup\u003eb\u003c/sup\u003e, L\u0026thinsp;+\u0026thinsp;Ore\u0026thinsp;+\u0026thinsp;selinexor, TEDDi-R, L\u0026thinsp;+\u0026thinsp;Ore\u0026thinsp;+\u0026thinsp;selinexor, WBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eTT-Bu\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib, 12 days, continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBrain-deep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eCD79B\u003c/em\u003e, \u003cem\u003eMYD88\u003c/em\u003e, \u003cem\u003eNOTCH1\u003c/em\u003e, \u003cem\u003eTP53\u003c/em\u003e, \u003cem\u003ePIM1, DNMT3A\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eR-MTX\u0026thinsp;+\u0026thinsp;Ore, R-MTX\u0026thinsp;+\u0026thinsp;TMZ, R-THOP, R-MTX, TEDDi-R\u003csup\u003eb\u003c/sup\u003e, R-EPOCH\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eTT-Bu\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOrelabrutinib, 3 days, continuing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive, 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e\u003csup\u003ea\u003c/sup\u003eBrain was involved in the first relapse after one year\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e\u003csup\u003eb\u003c/sup\u003efor mobilization of stem cells\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e\u003csup\u003ec\u003c/sup\u003eaccording to IELSG scoring system, including basal ganglia, corpuscallosum, brain stem, cerebellum\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e\u003csup\u003ed\u003c/sup\u003eTT-Bu for pt 2, pt 6, pt 11, and pt 12 due to post multi-course chemotherapy with poor tolerance, latent tuberculosis infection, myelosuppresion after radiotherapy, and age\u0026thinsp;\u0026gt;\u0026thinsp;65 years old, respectively\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eFU\u003c/em\u003e, follow up; \u003cem\u003ePt\u003c/em\u003e, patients number; \u003cem\u003eNGS\u003c/em\u003e, next generation sequence; mo. Months; \u003cem\u003eASCT\u003c/em\u003e, autologous stem cell transplantation; \u003cem\u003eND\u003c/em\u003e, no data; \u003cem\u003eCR\u003c/em\u003e, complete remission; \u003cem\u003ePR\u003c/em\u003e, partial remission; \u003cem\u003ePD\u003c/em\u003e, progressive disease; \u003cem\u003ePFS\u003c/em\u003e, progression free survival; \u003cem\u003eOS\u003c/em\u003e, overall survival; \u003cem\u003eMTX\u003c/em\u003e, methotrexate; \u003cem\u003eR\u003c/em\u003e, rituximab; \u003cem\u003eL\u003c/em\u003e, lenalidomide; \u003cem\u003eE\u003c/em\u003e, etoposide; \u003cem\u003eZ\u003c/em\u003e, zanubrutinib; \u003cem\u003eTMZ\u003c/em\u003e, temozolomide; \u003cem\u003eP\u003c/em\u003e, prednisone; \u003cem\u003eMA\u003c/em\u003e, methotrexate, cytarabine; \u003cem\u003eR-CHOPE\u003c/em\u003e, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide; \u003cem\u003eR-COPADM1\u003c/em\u003e, rituximab, cyclophosphamide, vincristine, prednisone, adriamycin, methotrexate; \u003cem\u003eMATRix\u003c/em\u003e, rituximab, methotrexate, cytarabine, thiotepa; \u003cem\u003eR-MAD, r\u003c/em\u003eituximab, methotrexate, cytarabine, dexamethasone; \u003cem\u003eOre\u003c/em\u003e, orelabrutinib; \u003cem\u003eOre-MTDEA\u003c/em\u003e, orelabrutinib, methotrexate, temozolomide, dexamethasone; \u003cem\u003emotified TEDDi-R\u003c/em\u003e, temozolomide, teniposide, doxorubicin, orelabrutinib/ zanubrutinib, dexamethasone, rituximab; \u003cem\u003eR-THOP\u003c/em\u003e, rituximab, temozolomide, doxorubicin, vincristine,prednisone; \u003cem\u003eR-EPOCH, r\u003c/em\u003eituximab, etoposide, prednisone, doxorubicin, cyclophosphamide, vincristine; \u003cem\u003eCAR-T\u003c/em\u003e, chimeric antigen receptor T-cell; \u003cem\u003eWBRT\u003c/em\u003e, whole-brain radiotherapy; \u003cem\u003emTBC\u003c/em\u003e, modified thiotepa, busulfan, cyclophosphamide; \u003cem\u003eTT-Bu\u003c/em\u003e, thiotepa, busulfan; \u003cem\u003eTT-Cy, t\u003c/em\u003ehiotepa, cyclophosphamide\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eASCT and the associated complications\u003c/h2\u003e \u003cp\u003eThe median time from diagnosis to ASCT was 10.2 (range, 5.2‒102.1) months, and only 7 (51%) patients received ASCT within one year of diagnosis. Six patients received ASCT as first-line consolidation in CR/PR state. Moreover, 7 (58.3%) patients received mTBC conditioning regimen, 4 (33.3%) received TT-Bu, and one patient received TT-Cy, incorporating CAR-T cell infusion. Among 4 patients receiving TT-Bu, a reduced toxicity regimen due to reasons, such as poor tolerance post multi-course chemotherapy, latent tuberculosis infection, myelosuppression after radiotherapy, and age over 65 years old, respectively. The median dose of mononuclear cells (MNCs) and CD34\u0026thinsp;+\u0026thinsp;cells in the graft for infusion was 4.57 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e/kg (range, 3.06‒7.75) and 3.83 \u0026times; 10\u003csup\u003e6\u003c/sup\u003e/kg (range, 1.1‒9.51), respectively. All patients achieved sustained neutrophil recovery at a median of 9 (range, 7\u0026ndash;12) days and platelet engraftment at a median of 10 (range, 6\u0026ndash;12) days (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). All patients were in CR at the first efficacy evaluation following ASCT.\u003c/p\u003e \u003cp\u003eWith the modified thiotepa-based ASCT procedure, no TRM occurred. There was no hemorrhagic cystitis, sinusoidal obstruction syndrome (SOS), and cutaneous toxicity. The main complications during hospitalization were febrile neutropenia (83.3%) and diarrhea grade III (50.0%) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There were 3 (25%) patients with temporally acute delirium, including delirium, photis, time and/or location disorientation, which occurred during intravenous busulfan. Furthermore, 2 (16.7%) patients experienced oral mucositis grade III (16.7%), and 2 (16.7%) cases were found with septicemia, including one with Escherichia coli, the other one with carbapenem-resistant Enterobacteriaceae (CRE), klebsiella pneumoniae (KP). Besides, each patient experienced an epileptic seizure and implantation syndrome, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). All patients with these complications had favorable outcomes. Although no formal neurologic assessment was performed, no case of significant long-term cognitive dysfunction or decline was identified during follow-up.\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\u003eMain complications during hospitalization for HDC-ASCT (n\u0026thinsp;=\u0026thinsp;12)\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;12, %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFebrile neutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhea grade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute delirium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral mucositis grade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepticemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpileptic seizure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImplantation syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\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 \u003cem\u003eHDC-ASCT\u003c/em\u003e, high dose chemotherapy followed by autologous stem cell transplantation\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMaintenance therapy\u003c/h2\u003e \u003cp\u003eAll patients, except one case, enderwent maintenance therapy, beginning at a median time of 62 (range, 30\u0026ndash;245) days after ASCT. The majority (10/11, 90.9%) opted for BTKi, predominantly orelabrutinib (8/11, 72.7%) and zanubrutinib (2/11, 18.2%). One patient received individualized CD19 CAR-T therapy as consolidation on day\u0026thinsp;+\u0026thinsp;49 post-ASCT due to progressive disease before the trasplant. At the last follow-up, only one patient, who had been on zanubrutinib for eight months, discontinued due to a COVID-19 infection during the pandemic. The median duration of maintenance therapy was 42 (range, 3\u0026ndash;739) days, with 11 (91.7%) patients remaining in complete remission. The sole patient who declined maintenance therapy for financial reasons experienced a relapse on day\u0026thinsp;+\u0026thinsp;181 post-ASCT. However, the disease has since stabilized with the use of a BTKi, knetinib in a clinical trial (Registration No. CTR20200412) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eResponse and survival outcomes\u003c/h2\u003e \u003cp\u003eTreatment response and survival outcomes are vividly illustrated in the swimmer plots (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The total response rate of initial induction chemotherapy was high (10/12, 83.3%), while up to half of the patients (5/10, 50%) relapsed and 3 patients relapsed within one year. The salvage therapy for R/R PCNSL included multidrug combination chemotherapy, WBRT, and CAR-T (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Notably, 3 patients received CAR-T therapy in different clinical conditions. One of the two patients who had progressive disease before ASCT received CAR-T cell infusion on +\u0026thinsp;3d post-ASCT, while the other patient underwent an individual CAR-T therapy as consolidation in the early post-ASCT phase. Another one received CAR-T therapy for late relapse on +\u0026thinsp;554d post-ASCT. All of these 3 patients obtained sustained CR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe median follow-up time from initial treatment and ASCT was 19 (range, 8.9\u0026ndash;106) and 4.5 (range, 1.9\u0026ndash;34.7) months, respectively. The median OS from diagnosis was 19.1 (range, 10.2-106.6) months. The median PFS pre-ASCT was 8.3 (range, 5.2\u0026ndash;96.8) months. Moreover, the median PFS and OS from ASCT were both 4.5 (range, 1.9\u0026ndash;34.7) months (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The estimated 1- and 3-year PFS rates were 80.0% and 53.3%, while the estimated 1- and 3-year OS rates were both 100% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePCNSL is an aggressive lymphoma characterized with poor prognosis. HDC-ASCT as the first-line consolidation or salvage therapy can be a critical approach for PCNSL patients. Given the context of the high PFS, but also high TRM associated with the TBC conditioning regimen, this real-life, pilot study aimed to investigate the feasibility and efficacy of modified thiotepa-based conditioning regimens. The results highlighted that the mTBC/TT-Bu/TT-Cy protocol was well-tolerated and effective in terms of engraftment, complications, and lymphoma control.\u003c/p\u003e \u003cp\u003eThe utilization of HDC-ASCT in the initial treatment of newly diagnosed PCNSL or as salvage therapy for R/R patients who achieve a CR or PR to re-induction has been extensively investigated in several studies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Given the involvement of the central nervous system (CNS) in PCNSL, there are stringent requirements for the conditioning regimen. This regimen must not only overcome the intrinsic chemoresistance of lymphoma cells but also enhance disease control by achieving elevated CNS drug concentrations, thereby circumventing chemoresistance mediated by the BBB. Thiotepa, renowned for its 100% CNS penetrance, has emerged as a crucial agent in this context. Consequently, thiotepa-based conditioning regimens, such as TBC, have been developed, demonstrating significant improvements in patient outcomes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNumerous retrospective and prospective studies have examined ASCT in PCNSL using thiotepa-based conditioning regimens [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28 CR29 CR30 CR31 CR32 CR33\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Although the majority of these series are relatively small and encompass diverse patient populations, reported survival rates ranges from 51.4\u0026ndash;100% at 1 to 5 years. The most extensive observational cohort study to date, drawing from registry data from the Center for International Blood and Marrow Transplant Research and including 538 adult with PCNSL patients who underwent thiotepa-based ASCT (TBC, n\u0026thinsp;=\u0026thinsp;263; TT-BCNU, n\u0026thinsp;=\u0026thinsp;275), indicated that those who received TBC experienced significantly lower rates of relapse (11% vs. 15%) and disease-related death (7.6% vs. 12%), higher rates of TRM (14% vs. 9%), and similar 3-year OS rates (81% vs. 78%) compared to the TT-BCNU cohort [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Another substantial study involving 230 PCNSL patients, evaluating therapeutic outcomes within the French Network, demonstrated superior outcomes with TBC and TT-Bu compared to TT-BCNU in terms of relapse risk and PFS with no difference in OS, but a higher TRM for TBC. The risk of TRM and deaths related to progressive disease were 46% and 39% for TBC, 33% and 33% for TT-Bu, and 8% and 79% for TT-BCNU [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The 5-year relapse rates were 9%, 19%, and 34% in TT-Bu, TBC, and TT-BCNU groups, respectively (P\u0026thinsp;=\u0026thinsp;0.0002), and the PFS in the TBC\u0026thinsp;+\u0026thinsp;TT-Bu group was significantly longer than that in the TT-BCNU group. However, there was not significantly different in OS and PFS among the three groups compared with each other [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. On the other hand, the TBC regimen demonstrated numerically superior OS and PFS rates in a systematic review of 43 studies [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The rates of OS after 1, 2, 3, and 5 years were 95%, 90%, 87%, and 81% in the TBC setting; 91%, 75%, 77%, and 70% in the TT-BCNU setting; and 83%, 82%, 83%, and 72% in the TT-Bu setting, respectively. Meanwhile, the PFS rates were 88%, 86%, 82%, and 81% in the TBC group; 73%, 64%, 60%, and 46% in the TT-BCNU group; and 78%, 67%, 56%, and 56% in the TT-Bu group [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Another systematic review analyzed 13 prospective studies including 348 patients with PCNSL who underwent first-line ASCT [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The pooled relapse rate of four studies [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] on 111 patients with the TBC regimen was 4%, and that was 28% for six studies [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] on 195 patients with thiotepa combined with other drugs. Results from a prospective multicenter trial by the German Cooperative PCNSL study group of 32 R/R PCNSL patients with TT-BCNU-ASCT revealed that 2-year PFS and 5-year OS rates were 56.1% and 55.6%, respectively. Notably, 3 (12.5%) patients experienced transplantation-related deaths after ASCT, including 2 patients with fatal sepsis and one case of treatment-associated CNS toxicity. Additionally, 14 (43.8%) cases resulted in death due to disease progression [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In a large multicenter retrospective analysis of ASCT with TBC in 79 R/R PCNSL patients, the 2- and 5-year event free survival (EFS) and DFS were 37.8% and 49.5%, respectively. Besides, there were 6 patients who died due to treatment-related toxicity after ASCT, 2 of whom were septic [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. A prospective, single-center phase-2 study on 26 patients with TBC-ASCT revealed that 2-, 3, and 5-year PFS and OS rates were all 81%, and 3 patients died of transplant-related complications, including acute Stevens-Johnson syndrome, septic shock, and fatal chronic colitis of undetermined etiology, potentially representing graft-versus-host disease [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A retrospective analysis of 46 patients with PCNSL in CR1 who underwent transplantation using a TBC-based conditioning regimen indicated that the estimated of 2-year OS and PFS rates were 95% and 92%, respectively, while the 2-year TRM rate was 2.9% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Results from the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS study of 44 patients with PCNSL who underwent TBC-ASCT as a first-line treatment indicated that the 2-year EFS was 87%, and the 2- and 4-year OS were both 66% [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], and the long-term results of this study revealed that the 8-year EFS and OS were 67% and 69%, respectively [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Moreover, 5 patients died as a result of TRM at 15, 16, 45, 169, and 220 days after ASCT, of whom 4 deaths (80%) caused by infectious complications [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Cote G. et al demanstrated that 37.5% (6/16) of patients with PCNSL had a documented infection during their ASCT course with TBC [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Montemurro M. et al. reported 5 (5/16, 31.3%) cases of infectious complications and during TT-Bu-ASCT, with 2 patients dying of septic causes at 6 and 36 days after ASCT.\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\u003eComparison with other thiotepa-based conditioning regimens for ASCT recipients with PCNSL\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. ASCT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eASCT setting\u003c/p\u003e \u003cp\u003eline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRegimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNeutrophils\u003c/p\u003e \u003cp\u003erecovery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePlatelets\u003c/p\u003e \u003cp\u003erecovery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ge;Grade III non-haematological toxicity (top, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTRM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDRM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePFS/EFS/DFS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIllerhaus et al. (2006)\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-BCNU\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFN, 52.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5y: 8.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5y: 87%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKasenda B. et al. (2012)\u003csup\u003e28\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-BCNU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerreri AJM, et al. (2017) \u003csup\u003e22\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-BCNU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFN or infection, 29.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 77%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKasenda B. et al. (2017) \u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSalvage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRituximab\u0026thinsp;+\u0026thinsp;TT-BCNU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eInfection, 65.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e43.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5y: 55.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 56.1%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchorb E, et al. (2017) \u003csup\u003e41\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst, 15\u003c/p\u003e \u003cp\u003eSalvage, 37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-BCNU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 70.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 62%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMontemurro M. et al. (2007) \u003csup\u003e29\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eInfection, 31.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e31.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 48%\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSanders S. et al. (2019) \u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3y: 92.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3y: 88.9%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchorb E, et al. (2020) \u003csup\u003e30\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eInfection, 7.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 92.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 92.9%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSoussain C. et al. (2008) \u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst, 15\u003c/p\u003e \u003cp\u003eSalvage, 12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eneurologic toxicity, 18.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCote G. et al. (2012) \u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMucositis, 81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3%\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1y: 93%\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1y: 90%\u003csup\u003ec,b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSoussain C. et al. (2012) \u003csup\u003e32\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSalvage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eInfection, 2.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5y: 51.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5y: 37.8%\u003csup\u003ed\u003c/sup\u003e, 49.5%\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWelch MR. et al. (2015) \u003csup\u003e33\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSalvage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFN, 33.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3y: 100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3y: 100%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOmuro A. et al. (2015) \u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFN, 42%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 81%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeFilipp Z. et al. (2017) \u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMucositis, 35%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 92%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHouillier C. et al. (2019) \u003csup\u003e34\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFN, 100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2y: 66%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2y: 87%\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScordo, M. et al. (2021) \u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC, 263\u003c/p\u003e \u003cp\u003eTT-BCNU, 275\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14%\u003c/p\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.6%\u003c/p\u003e \u003cp\u003e12%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3y: 81%\u003c/p\u003e \u003cp\u003e3y: 78%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3y: 75%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e3y: 76%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchenone L, et al. (2022) \u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst,119\u003c/p\u003e \u003cp\u003eSalvage, 111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBC, 142\u003c/p\u003e \u003cp\u003eTT-Bu, 24\u003c/p\u003e \u003cp\u003eTT-BCNU, 64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFN, 98%\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46%\u003c/p\u003e \u003cp\u003e33%\u003c/p\u003e \u003cp\u003e8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e39%\u003c/p\u003e \u003cp\u003e33%\u003c/p\u003e \u003cp\u003e79%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5y: ~ 70%\u003c/p\u003e \u003cp\u003e5y: ~ 88%\u003c/p\u003e \u003cp\u003e5y: ~ 54%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5y: ~ 64%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e5y: ~ 82%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e5y: ~ 57%\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003csup\u003ea\u003c/sup\u003eWBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003csup\u003eb\u003c/sup\u003eincludes total of PCNSL and SCNSL\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003csup\u003ec\u003c/sup\u003ePFS\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003csup\u003ed\u003c/sup\u003eEFS\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003csup\u003ee\u003c/sup\u003eDFS\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003csup\u003ef\u003c/sup\u003eincludes total of thiotepa-based patients\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eASCT\u003c/em\u003e, autologous stem cell transplantation; \u003cem\u003ePCNSL\u003c/em\u003e, primary central nervous system lymphoma; \u003cem\u003eTRM\u003c/em\u003e, transplantation-related mortality; \u003cem\u003eDRM\u003c/em\u003e, disease-related mortality; \u003cem\u003eOS\u003c/em\u003e, overall survival; \u003cem\u003ePFS\u003c/em\u003e,\u003c/p\u003e \u003cp\u003eprogression free survival; \u003cem\u003eEFS\u003c/em\u003e, event free survival; \u003cem\u003eDFS\u003c/em\u003e, disease free survival; \u003cem\u003eTT-BCNU\u003c/em\u003e, thiotepa, carmustine; \u003cem\u003eFN\u003c/em\u003e, febrile neutropenia; \u003cem\u003eTT-Bu\u003c/em\u003e, thiotepa, busulfan; \u003cem\u003eTBC\u003c/em\u003e, thiotepa, busulfan, cyclophosphamide\u003c/p\u003e \u003cp\u003eAlthough preliminary studies on thiotepa-based ASCT have been conducted on small and heterogeneous patients cohorts, making interpretation challenging, these findings stronglysuggest a potential benefit for TBC-ASCT in PCNSL. However, the TRM, particularly caused by serious infections, warrants attention, and the optimal conditioning regimen remains elusive. Collectively, these studies indicated that the benefit to risk ratio of TBC-ASCT could be improved through dose adjustments to the conditioning regimen. In the present study, patients received a mTBC regimen, where the cyclophosphamide dosage was reduced to 1 g/m\u003csup\u003e2\u003c/sup\u003e/d for two days compared with the traditional TBC regimen of 60 mg/kg/d for two days. For fragile patients, the decision to use TT-Bu was made by the physician, while TT-Cy was utilized for ASCT incorporated with CAR-T therapy (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). With a median follow-up time of 4.5 (range, 1.9\u0026ndash;34.7) months, all patients achieved CR at the first assessment after ASCT, with only one patient experiencing disease progression at 6 months post-ASCT. All patients were alive at the last follow-up. The estimated 1- and 3-year PFS rates were 80.0% and 53.3%, respectively, while both the 1- and 3-year OS rates were 100% (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Although 2 (16.7%) cases developed septicemia, one due to Escherichia coli and the other due to CRE, specifically KP, both patients recovered with favorable outcomes. It is noteworthy that no TRM occurred in this series.\u003c/p\u003e \u003cp\u003eHematopoietic reconstitution is the primary efficient and safe indicator for conditioning regimen, and early implementation of transplantation significantly reduces the risk of transplantation-related complications and deaths, particularly severe infections. Previous studies on TBC or TT-Bu-ASCT have reported median time to neutrophil and platelet recovery of 8\u0026ndash;11 days and 11\u0026ndash;18 days, respectively [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In the present study, all patients achieved sustained hematological recovery earlier than previous reports, with neutrophil recovery at a median time of 9 (7\u0026ndash;12) days and platelet engraftment at a median time of 10 (6\u0026ndash;12) days. The reported main grade 3/4 complications during thiotepa-based conditioning with ASCT were febrile neutropenia (29.3\u0026ndash;100%), infection (7.7\u0026ndash;65.6%), oral mucositis (4\u0026ndash;81%), diarrhea (4\u0026ndash;42%), acute delirium/neurologic toxicity (6.25\u0026ndash;22%), cutaneous toxicity (0\u0026ndash;24%), engraftment syndrome (0\u0026ndash;17%), bronchial obstruction (0\u0026ndash;13%), epileptic seizure (0\u0026ndash;9%), cardiac arrhythmias or cardiac failure (0\u0026ndash;8%), hemorrhagic cystitis (0\u0026ndash;6%), SOS (0\u0026ndash;5%), etc. [\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. A large retrospective study reported as high as 98% for febrile neutropenia (FN) and 81% for oral mucositis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A randomized Phase II study indicated that FN occurred in all 44 patients, and nonhematologic and noninfectious grade 3 or higher toxicities included alopecia (100%) and oral or gastrointestinal mucositis (77%) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Cote G. et al reported that 31.3% (6/16) of patients had a documented infection during their ASCT course with TBC, and 81% (13/16) had grade 3 and 4 mucositis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In another prospective study, the most common grade 3 or higher toxicities were FN (11/26, 42%), infection (7/26, 26.9%), and skin rash (3/26, 11.5%) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. DeFilipp Z et al.\u0026rsquo;s research indicated that the most common toxicities were infections (18/46, 39.1%) and severe mucositis (16/46, 35%), with a higher rate of engraftment syndrome (8/46, 17%) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In the present study, the types of common complications were consistent with previous reports but with much lower incidences, especially in infection (16.7%), diarrhea (50%), and oral mucositis (16.7%). Notably, the incidence of transient acute delirium (25%) with a favorable outcome appeared to be relatively high. It is noteworthy that none of these toxicities led no TRM.\u003c/p\u003e \u003cp\u003eIn the present study, the outcomes confirmed the encouraging tolerance and safety of the mTBC/TT-Bu/TT-Cy-ASCT protocol. However, longer-term follow-up is essential to definitively assess survival benefits. Two long-term randomized trial results of PCNSL patients treated with TBC/TT-BCNU followed by ASCT have indicated that ASCT appears to be highly effective in preventing relapses and improving functions and quality of life. The estimated 8-year EFS and OS rates were reported as 67% and 69% [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], and the 7-year OS was 70% [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], confirming that present study will likely yield promising long-term survival results. In addition to continued patient follow-up, prospective clinical trials will be conducted to accurately assess patients who would benefit from either the mTBC or TT-Bu regimens.\u003c/p\u003e \u003cp\u003eThe optimal timing for ASCT is clear, in which undergoing ASCT in the first-line setting is superior to the salvage setting [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The report of French Network revealed that the 5-year OS of ASCT in the first-line treatment and at first-relapse PCNSL was 80% and 50%, respectively [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Another retrospective international study suggested that the 2-year PFS and OS rates were both 80% for patients undergoing ASCT as first-line treatment, and those were 54.0% and 65.6% for patients undergoing ASCT as second or subsequent line of treatment, respectively [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. A prospective phase II multicenter study showed that the 2-year OS and 2-year PFS rates was 69% and 58% after TBC-HSCT as the first-line and salvage treatment for PCNSL patients, respectively [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. A systematic review of 43 studies on ASCT indicated that the OS rates were 94%, 86%, 82%, and 70% at 1, 2, 3, and 5 years in the consolidation setting, and 75%, 63%, 56%, and 54% at the same intervals in the salvage/relapse settings. Additionally, the overall risk of relapse at 5 years was 24% in the consolidation setting and 29% in the salvage/relapse settings. Besides, the pooled TRM rates were 1% and 4% in patients who underwent ASCT in the consolidation and salvage/ relapse settings [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. These results indicated that patients who had chemosensitive disease and received early HDC-ASCT as first-line consolidation treatment exhibited a better prognosis, as well as superior survival. The main changes in the latest European Association of Neuro-Oncology (EANO) guidelines for treatment of PCNSL versus previous guideline include strengthened evidence for the consolidation with ASCT in the first-line treatment [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In the present study, half of the patients received ASCT as the fist-line consolidation and salvage treatment, respectively. All patients except one, who declined maintenance therapy due to financial reasons, experienced relapse at +\u0026thinsp;181d post-ASCT, while they returned to sustained CR. Due to the limited number of cases, relatively short-term follow-up, and all patients being alive, no survival comparison was conducted.\u003c/p\u003e \u003cp\u003eBecause PCNSL is a special subtype of DLBCL, the prognosis of PCNSL is significantly worse than that of systemic DLBCL with a high rate of recurrence, particularly in the first 2 years after treatment [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Furthermore, when recurrence occurs, it mainly results in a devastating and irreversible impact on neurologic function. Therefore, maintenance therapy, immune cell therapy, and the utilization of targeted agents based on the molecular and biological properties of the disease may promote precision medicine, potentially leading to long-term disease-free survival and even cure [\u003cspan additionalcitationids=\"CR45 CR46\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. However, the questions of whether, when, and which maintenance therapies provide benefit for PCNSL patients remain to be addressed [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Tsang M. et al. performed a narrative review on the rationale for maintenance strategies in PCNSL patients, and indicated that the overall role of maintenance therapy may potentially improve survival and preserve quality of life and function in a vulnerable, older patient population [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Baireya S. et al. evaluated the possible role of maintenance treatment for PCNSL patients, and they pointed out that high-risk and elderly patients, who often experience a high relapse rate, short PFS, and OS, should be considered for maintenance treatment [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. In the present study, upon physician recommendation, all patients except one received maintenance therapy, with 9 patients starting within 3 months after ASCT. All patients who underwent maintenance therapy were in CR, and the longest duration of maintenance exceeded 2 years, indicating the effectiveness and reasonable tolerability of post-ASCT maintenance. The drugs used for maintenance included MTX, rituximab, lenalidomide, procarbazine, temozolomide, programmed cell death-1 (PD-1) inhibitors, thiotepa, and BTKi [\u003cspan additionalcitationids=\"CR50 CR51 CR52 CR53 CR54 CR55 CR56 CR57\" citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. In the present study, the majority of patients received BTKi for maintenance therapy because of its excellent performance in PCNSL as reported previously [\u003cspan additionalcitationids=\"CR60 CR61 CR62\" citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. A small scale study suggested that anti-CD19 CAR-T cell therapy appeared feasible for patients with R/R PCNSL [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. A phase I/II clinical trial and some case reports demonstrated the safety and efficacy of CAR-T cells with some durable responses [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan additionalcitationids=\"CR66\" citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e]. Moreover, several trials indicated that combining CAR-T cell administration with ASCT was safe and efficacious, and its long-term efficacy was further improved in patients with B-cell NHL, including PCNSL [\u003cspan additionalcitationids=\"CR69 CR70 CR71\" citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]. In the present study, there were 3 R/R PCNSL patients who received CAR-T cell therapy, including one who received infusion of CAR-T cells on +\u0026thinsp;3d post-ASCT, and one who underwent individual CAR-T therapy as consolidation on +\u0026thinsp;49d post-ASCT, and one who received CAR-T therapy for late relapse on +\u0026thinsp;554d post-HSCT. All of these three patients achieved sustained CR. This small-scale, real-life study indicated the safety and feasibility of different clinical application scenarios of CAR-T and HDC-ASCT for PCNSL, while the optimal combined application needs to further investigation.\u003c/p\u003e \u003cp\u003eThe present study has notable limitations, including the small sample size and relatively short follow-up. However, it is noteworthy that patients in this study were enrolled consecutively and underwent a consistent protocol for HDC-ASCT, ensuring the reliability of the conclusions drawn. This study presented real-life outcomes of PCNSL patients treated with a modified thiotepa-based conditioning regimen followed by ASCT. The findings provided valuable insights. Firstly, the modified thiotepa-based conditioning regimen and ASCT should be considered as intensified first-line consolidation therapy for PCNSL. Secondly, optimal patient selection criteria for mTBC or TT-Bu regimens need to be carefully stratified. Lastly, the utilization of TT-Cy for ASCT combined with CAR-T therapy should be further investigation in a larger patient cohort. Long-term survival outcomes will require validation in the future larger-scale follow-up research.\u003c/p\u003e \u003cp\u003eIn conclusion, this study assessed the modified thiotepa-based conditioning regimens and confirmed their safety and efficacy in ASCT for PCNSL patients. It made a significant contribution to the utilization of HDC-ASCT for PCNSL, supporting the ongoing interest in thiotepa-based conditioning regimens. Additionally, this study highlighted the trend towards integrated, multi-measure management of PCNSL.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHongmei J\u0026nbsp;was responsible for the conception and design of the study;\u0026nbsp;Yan L and Hongmei J designed the study. Yan L, Sen L, and Fang B collected and interpreted the data. Yan L\u0026nbsp;analyzed the data\u0026nbsp;and drafted the manuscript. Lan M, Wei Z, and Ping Y\u0026nbsp;provided study patients and valuable advice; Fei D and JiJun W\u0026nbsp;supervised the clinical protocol\u0026nbsp;and provided the expert consultations. Yan L and Hongmei J revised the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the special fund of the National Clinical Key Specialty Construction Program, P.R. China (2023), Beijing Municipal Natural Science Foundation (7232202), Beijing Bethune Charitable Foundation (J202201E023), Key Clinical Projects of Peking University Third Hospital (No.BYSYDL2021006).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patients and their families who contributed to this study. The authors would also like to acknowledge the doctors and nurses in our department for taking care of these patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData accessibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare they have no potential conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by The Ethics Committee of Peking University Third Hospital，and signed informed consents were obtained from all patients in accordance with principles of Declaration of Helsinki.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFerreri AJM, Calimeri T, Cwynarski K, Dietrich J, Grommes C, Hoang-Xuan K, Hu LS, Illerhaus G, Nayak L, Ponzoni M, Batchelor TT (2023) Primary central nervous system lymphoma. 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Blood cancer journal 11(7):131. https://doi.org/10.1038/s41408-021-00523-2\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"primary central nervous system lymphoma, thiotepa-based conditioning, high dose chemotherapy, autologous stem cell transplantation","lastPublishedDoi":"10.21203/rs.3.rs-4403718/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4403718/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHigh-dose chemotherapy followed by autologous stem cell transplantation (HDC\u0026ndash;ASCT) is a promising approach for patients with primary central nervous system lymphoma (PCNSL). Encouraging results have been reported with thiotepa-based conditioning; however, there is currently no consensus on the optimal conditioning regimens. To improve the tolerance and efficacy of ASCT with thiotepa-based conditioning, this retrospective, single-arm, pilot study was conducted, including 12 PCNSL patients who received ASCT with modified thiotepa-based conditioning regimens. It was found that 6 patients received ASCT as a first-line consolidation in complete response (CR)/partial response (PR) state, and 6 cases underwent salvage treatment. Among the patients, 7 (58.3%) received the mTBC conditioning regimen, 4 (33.3%) received TT-Bu, and one patient was incorporated with chimeric antigen receptor T-cell (CAR-T) cell infusion with the TT-Cy regimen. All patients achieved sustained neutrophil recovery within a median of 9 (range, 7\u0026ndash;12) days and platelet engraftment within a median of 10 (range, 6\u0026ndash;12) days. Furthermore, all patients were in CR status at the initial efficacy evaluation following ASCT. The main complications during hospitalization were febrile neutropenia (83.3%) and diarrhea grade 3 (50.0%). No transplantation- related mortality occurred. Maintenance therapy post-ASCT was administered in 11 cases, demonstrating its effectiveness and favorable tolerability. The estimated 1- and 3-year progression-free survival (PFS) following ASCT were 80.0% and 53.3%, respectively, while the estimated 1-and 3-year overall survival (OS) were both 100%. This study presented the modified thiotepa-based conditioning regimens and confirmed their safety and efficacy with ASCT for PCNSL patients.\u003c/p\u003e","manuscriptTitle":"The notable outcomes of modified thiotepa-based conditioning followed by autologous stem cell transplantation in primary central nervous system lymphomas: A real-life pilot study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-31 16:14:35","doi":"10.21203/rs.3.rs-4403718/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"be9f7acc-e46a-45f9-ab99-5b4a2891e40c","owner":[],"postedDate":"May 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-07T08:12:19+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-31 16:14:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4403718","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4403718","identity":"rs-4403718","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}