Real-world analysis of autologous stem cell transplantation in primary central nervous system lymphoma using Taiwan Blood and Marrow Transplantation Registry (TBMTR)

Real-world analysis of autologous stem cell transplantation in primary central nervous system lymphoma using Taiwan Blood and Marrow Transplantation Registry (TBMTR) | 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 Real-world analysis of autologous stem cell transplantation in primary central nervous system lymphoma using Taiwan Blood and Marrow Transplantation Registry (TBMTR) Po-Tsen Liu, Pei-An Fu, Ming Yao, Bor-Sheng Ko, Liang-Tsai Hsiao, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6846411/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 Although high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is an established consolidation strategy for primary central nervous system lymphoma (PCNSL), real-world data remain limited, especially in Asia. This retrospective multicenter study analyzed 65 PCNSL patients from the Taiwan Blood and Marrow Transplantation Registry (TBMTR) who underwent HDC/ASCT between 2012 and 2022. Patients were classified into the frontline (n = 47) and salvage (n = 18) HDC/ASCT groups. The 2-year overall survival (OS) and relapse-free survival (RFS) rates were 68.3% and 58.8% in the frontline group, and 69.8% and 58.4% in the salvage group, respectively. Thiotepa-based regimens showed no survival advantage; the 2-year OS was 58.3% for thiotepa recipients versus 76.6% for non-thiotepa recipients (p = 0.84). This finding may be attributed to limited access to thiotepa and the small number of patients who received thiotepa-based induction chemotherapy. Disease relapse or progression was the primary cause of mortality across all groups, whereas infection or other non-relapse mortality was infrequent. In this study, HDC/ASCT improved OS and RFS for PCNSL patients in both frontline and salvage settings, although the thiotepa-based conditioning regimen showed no survival benefit. non-Hodgkin's lymphoma primary CNS lymphoma autologous stem cell transplantation frontline intensification Figures Figure 1 Figure 2 Figure 3 Introduction Primary central nervous system lymphoma (PCNSL) is a rare, highly aggressive form of extranodal non-Hodgkin lymphoma confined to the central nervous system (CNS), including the brain, spinal cord, meninges, and vitreoretinal region [ 1 ]. The disease poses significant clinical challenges due to its unique neuroanatomical localization, aggressive progression, high relapse rates, and treatment-associated complications. The standard induction regimen for PCNSL typically includes high-dose methotrexate-based chemotherapy, followed by consolidation with additional chemotherapy, whole-brain radiotherapy (WBRT), or high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) [ 2 , 3 ]. While HDC/ASCT was initially used as salvage therapy for relapsed or refractory PCNSL [ 4 ], it is now also incorporated as a consolidation option in frontline treatment protocols. Compared with WBRT, which is associated with significant neurocognitive decline, HDC/ASCT offers a less neurotoxic alternative with promising long-term outcomes [ 5 – 8 ]. Randomized controlled trials support this therapeutic approach, demonstrating extended progression-free survival (PFS) in newly diagnosed patients who undergo HDC/ASCT as consolidation therapy [ 5 , 7 , 9 , 10 ]. However, real-world evidence remains scarce, especially in Asia, and the overall survival (OS) benefit of frontline HDC/ASCT remains controversial. Moreover, the conditioning regimen used during transplantation affects outcomes. Thiotepa, an alkylating agent that effectively penetrates the blood-brain barrier, was introduced for treating PCNSL and subsequently incorporated into HDC/ASCT conditioning regimens [ 11 ]. Observational cohort studies suggest that thiotepa-based regimens may improve survival despite their association with higher toxicity and increased non-relapse mortality (NRM), particularly with combinations such as thiotepa, busulfan, and cyclophosphamide (TBC) [ 12 , 13 ]. Limited access to thiotepa in East Asia, including Taiwan, has restricted its clinical use. This limitation may influence real-world outcomes compared with those from prospective trials, underscoring the need for further investigation. To investigate the outcomes and benefits of consolidative autologous transplantation following induction chemotherapy, and to evaluate the impact of conditioning regimens during the transplantation, we retrospectively analyzed data from the Taiwan Blood and Marrow Transplantation Registry (TBMTR) cohort. Subjects and Methods Data acquisition This retrospective observational study used data from the TBMTR. Seventeen hospitals participating in the Taiwan Society of Blood and Marrow Transplantation contributed data to the TBMTR. Patients registered in the TBMTR who underwent HDC/ASCT between January 2012 and December 2022 were included. Individuals who received allogeneic HDC/ASCT were excluded. Relevant variables recorded in the TBMTR included age, sex, pre-HDC/ASCT disease status, induction therapies, conditioning regimens, and salvage therapies. Patient Classification and Outcome Assessment Enrolled patients were categorized into two groups: the frontline HDC/ASCT group (those without reported relapse before transplantation) and the salvage HDC/ASCT group (patients with reported relapse before transplantation). Treatment response before HDC/ASCT was assessed by local neuroradiologists at individual centers using contrast-enhanced magnetic resonance imaging. Evaluations followed the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria for PCNSL, ensuring consistency in treatment outcome assessments. Notably, ophthalmologic and cerebrospinal fluid (CSF) assessments were not routinely performed. Final response interpretations and treatment decisions were made by local hematologists [ 14 ]. The study aimed to evaluate OS and relapse-free survival (RFS) in PCNSL patients undergoing frontline or salvage HDC/ASCT. OS was defined as the time from transplantation to death from any cause or last follow-up, whereas RFS was measured from transplantation to disease relapse, death, or last follow-up. Statistical Analysis OS and RFS probabilities were estimated using the Kaplan–Meier method. All statistical analyses and graphical representations were performed using RStudio software (version 2024.12.0 + 467). A p-value < 0.05 was considered statistically significant. Results Patient Characteristics This study analyzed data from 65 PCNSL patients in the TBMTR between 2012 and 2022. Forty-seven patients (73.2%) were classified into the frontline HDC/ASCT group (Table 1 ), and the remaining 18 (26.8%) into the salvage HDC/ASCT group. The median age of all patients was 57 years, and the oldest patient was 78. The median follow-up for all patients was 34.6 months: 19.9 months in the frontline HDC/ASCT group, and 63.2 months in the salvage group. The median time from initial diagnosis to HDC/ASCT was 6.7 months in the frontline group, whereas it was significantly longer (32.4 months) for the salvage group. Fourteen patients (21.5%) were hepatitis B virus carriers. Only one patient (1.5%) had human immunodeficiency virus infection who was included in the frontline group. Elevated lactate dehydrogenase (LDH) levels before HDC/ASCT were observed in 20 patients (30.8%), predominantly in the frontline group. Twenty percent of patients had received radiotherapy before HDC/ASCT, with a higher percentage (38.9%) in the salvage group. Table 1 Patients’ baseline characteristics Total Frontline Salvage Patients, n (%) 65 47 (73.2) 18 (26.8) Age, median (range) 57 (38–78) 58 (40–78) 54 (38–68) Sex, male, n (%) 37 (56.9) 24 (51.1) 13 (72.2) Follow-up time, months, median (Range) 34.6 (5.8-156.6) 19.9 (5.8-150.5) 63.2 (36.1-156.6) Diagnosis time 2012–2017, n (%) 29 (44.6) 16 (34.0) 13 (72.2) 2018–2022, n (%) 36 (55.4) 31 (66.0) 5 (27.8) Median time from diagnosis to HDC/ASCT, months (Range) 8.1 (3.6–65.8) 6.7 (3.6–49.8) 32.4 (10.1–65.8) HBV status HBV carrier, n (%) 14 (21.5) 9 (19.1) 5 (27.8) Resolved HBV, n (%) 39 (55.4) 30 (63.8) 9 (50.0) HIV status, n (%) 1 (1.5) 1 (2.1) 0 (0.0) Elevated LDH, n (%) 20 (30.8) 17 (36.2) 3 (16.7) Radiotherapy exposure before HDC/ASCT, n (%) 13 (20.0) 6 (12.8) 7 (38.9) Chemotherapy regimens before HDC/ASCT, n (%) 1 39 (60.0) 37 (78.7) 2 (11.1) 2 9 (13.8) 0 (0.0) 9 (50.0) > 2 7 (10.7) 0 (0.0) 7 (38.9) Regimens of induction chemotherapy, n HDMTX based 54 37 18 CYVE 5 0 5 Temozolomide/R/Ara-C 0 0 0 R-MATRix 0 0 0 Other 12 0 13 Intrathecal therapy (n, %) 39 (60.0) 31 (66.0) 8 (44.4) Best response before HDC/ASCT, n (%) CR 29 (44.6) 23 (48.9) 6 (33.3) PR 30 (46.2) 22 (46.8) 8 (44.4) <PR 6 (9.2) 2 (4.3) 4 (22.2) Conditioning regimen, n (%) Thiotepa-based 36 (55.4) 29 (61.7) 7 (38.9) TT-BCNU +/- R 30 (83.3) 25 (86.2) 5 (71.4) TBC +/- R 5 (13.9) 3 (10.3) 2 (28.6) Other 1 (2.8) 1 (3.4) 0 (0.0) Thiotepa total dose 10mg/kg 22 (61.1) 19 (65.5) 3 (42.9) 20mg/kg 9 (25.0) 7 (24.1) 2 (28.6) Other a 5 (13.9) 3 (10.3) 2 (28.6) Non-thiotepa based 29 (44.6) 18 (38.3) 11 (61.1) BEAM +/- R 24 (82.8) 16 (88.9) 8 (72.7) BeEAM +/- R 2 (6.9) 1 (5.5) 1 (9.1) Other 3 (10.3) 1 (5.5) 2 (18.2) Ara-C: cytarabine, BeEAM: bendamustine, etoposide, cytarabine, melphalan, BEAM: carmustine, etoposide, cytarabine, melphalan, CR: complete remission, CYVE: Cytarabine and etoposide, HBV: hepatitis B virus, HDC/ASCT: high-dose chemotherapy with autologous stem-cell transplant, HDMTX: High-dose methotrexate, HIV: human immunodeficiency virus, LDH: lactate dehydrogenase, PR: partial remission, R: rituximab, R-MATRix: methotrexate, cytarabine, thiotepa and rituximab, TBC: thiotepa, busulfan, and cyclophosphamide, TT-BCNU: thiotepa, carmustine a 4 patients at 250 mg/m² for 3 days in TBC regimen, while 1 had an unknown dose. In the frontline group, 37 patients received high-dose methotrexate (HDMTX)-based regimens, whereas the remaining 10 received local therapies or immunotherapy without systemic chemotherapy before consolidative HDC/ASCT. Patients in the frontline group treated with HDMTX-based regimens may have received alternating R-MATRix, cytarabine, or addition of temozolomide. In the salvage group, most patients received two or more chemotherapy lines before HDC/ASCT. Chemotherapy regimens in the salvage group were diverse. Intrathecal chemotherapy was administered to 31 patients (66.0%) in the frontline group and 8 (44.4%) in the salvage group. Before transplantation, 23 patients (48.9%) in the frontline group and 6 (33.3%) in the salvage group achieved complete remission (CR). Twenty-two patients (46.8%) in the frontline group and 8 (44.4%) in the salvage group had partial remission (PR) before HDC/ASCT. Two (4.3%) frontline patients and 4 (22.2%) salvage patients underwent HDC/ASCT without achieving remission. Over half the patients (61.7%) in the frontline group received thiotepa-based conditioning regimens for HDC/ASCT, whereas only 7 (38.9%) in the salvage group received such regimens. Thiotepa-based regimens mainly consisted of TT-BCNU (thiotepa, carmustine [BCNU]) or TBC (thiotepa, busulfan, and cyclophosphamide), with or without rituximab. The non-thiotepa group primarily received the BEAM regimen (BCNU, etoposide, cytarabine, and melphalan), with or without rituximab. Thiotepa was predominantly administered at a total dose of 10 mg/kg over the conditioning course. Survival Outcomes in the Frontline HDC/ASCT Group For the frontline HDC/ASCT group, 2- and 3-year OS rates were 68.3% (95% CI, 54.5–85.6) and 58.5% (95% CI, 42.8–79.9), respectively. The 2- and 3-year RFS rates were 58.8% (95% CI, 45.3–76.3) and 53.4% (95% CI, 38.8–73.7), respectively (Fig. 1 a, 1 b). For patients in the frontline HDC/ASCT group receiving thiotepa-based conditioning regimens, 2- and 3-year OS rates were both 58.3% (95% CI, 37.2–91.2). In the non-thiotepa group, the 2-year OS rate was 76.6% (95% CI, 58.8–99.7) and the 3-year OS rate was 62.7% (95% CI, 42.7–92.0) (p = 0.84) (Fig. 2 a). Moreover, for the thiotepa-based conditioning group, the 2- and 3-year RFS rates were both 58.0% (95% CI, 40.9–82.2), whereas for the non-thiotepa group, these rates were 58.8% (95% CI, 39.2–88.3) and 51.5% (95% CI, 31.8–83.5), respectively (Fig. 2 b); this difference was not statistically significant (p = 0.87). Survival Outcomes in the Salvage HDC/ASCT Group In the salvage HDC/ASCT group, the 2- and 3-year OS rates were both 69.8% (95% CI, 48.4–100). Additionally, the 2- and 3-year RFS rates were both 58.4% (95% CI, 39.0–87.7) (Fig. 3 a, 3 b). Mortality and Infection-Related Complications in HDC/ASCT Patients All patients achieved engraftment, with a comparable median engraftment time of 9 days in both conditioning groups ( Supplementary Fig. 1 ). Among the 65 patients who underwent HDC/ASCT, 20 (30.8%) died during follow-up (Table 2 ). Disease progression was the primary cause (13 deaths), followed by infection (5 deaths). Sixteen deaths occurred in the frontline HDC/ASCT group: 8 in the thiotepa-based subgroup and 8 in the non-thiotepa group ( Supplementary table 1 ). Of these 8 deaths in the thiotepa-based subgroup, disease relapse or progression was the leading cause (5 patients), followed by infection (3 patients). During follow-up, 20 of the 65 patients experienced disease relapse: 13 in the frontline group and 7 in the salvage group (Table 2 ). Table 2 Cause of mortality in autologous HDC/ASCT and salvage chemotherapy following relapse Total, n (%) Frontline, n (%) Salvage, n (%) Patients, n 65 47 18 Mortality, n (%) 20 (30.8) 16 (34.0) 4 (22.2) Major cause of mortality Disease-related 13 (65.0) 10 (62.5) 3 (75.0) Infection 5 (25.0) 5 (31.3) 0 (0.0) Other 2 (10.0) 1 (6.3) 1 (25.0) Relapse, n (%) 20 (30.8) 13 (27.7) 7 (38.9) Salvage regimen, n HDMTX based 6 (15.0) 4 (7.7) 2 (28.6) CYVE 1 (5.0) 1 (7.7) 0 (0.0) Rituximab/Lenalidomide 2 (10.0) 2 (15.4) 0 (0.0) ICE 2 (10.0) 0 (0.0) 2 (28.6) Other or unknown 9 (45.0) 6 (46.2) 3 (42.9) CYVE: Cytarabine, etoposide, HD C/ASCT: high-dose chemotherapy with autologous stem-cell transplant, HDMTX: High-dose methotrexate, ICE: ifosfamide, carboplatin and etoposide Infections were a major post-HDC/ASCT non-relapse event, particularly within the first 100 days. Among all 65 patients receiving HDC/ASCT, 25 (38.5%) developed infections (Table 3 ), with a higher incidence in the non-thiotepa group. Thirty-nine infection episodes were reported. Pneumonia was the most frequent infection in both conditioning groups, with bacterial pathogens being the predominant cause. Table 3 Post-transplant infection within 100 days Total Thiotepa Non-thiotepa Patients, n (%) 25 (38.5) 15 (32.1) 10 (55.6) Total events, n 39 26 13 Pneumonia, n (%) 14 (35.9) 8 (30.8) 6 (46.2) Urinary tract, n (%) 5 (12.8) 3 (11.5) 2 (15.4) Intra-abdominal, n (%) 3 (7.7) 2 (7.7) 1 (7.7) CRBSI, n (%) 5 (12.8) 2 (7.7) 3 (23.1) Soft tissue, n (%) 5 (12.8) 4 (15.4) 1 (7.7) CMV viremia, n (%) 4 (10.3) 4 (15.4) 0 (0.0) Other/unknown, n (%) 3 (7.7) 3 (11.5) 0 (0.0) Pathogens, events (%) Bacteria 22 (56.4) 13 (50.0) 9 (69.2) Virus 7 (17.9) 7 (26.9) 0 (0.0) Fungus 3 (7.7) 2 (7.7) 1 (7.7) Unknown 7 (17.9) 4 (15.4) 3 (23.1) CRBSI: Catheter-related bloodstream infection Discussion This retrospective observational study is Taiwan’s first multicenter analysis of autologous HDC/ASCT outcomes in PCNSL patients, focusing on the role of frontline HDC/ASCT and conditioning regimens. Our findings reaffirm HDC/ASCT as a feasible consolidation strategy, with 2-year OS and RFS rates that are consistent with previous international data from trials such as PRECIS [ 5 ] and IELSG 32[ 7 ], and other nationwide cohort studies [ 15 – 17 ]. The PRECIS study [ 5 ] compared HDC/ASCT to WBRT and showed a 2-year PFS benefit of 87% in the transplant group, although it focused on younger patients (aged 18–60). Similarly, the IELSG 32 study reported comparable 2-year OS (71%) and PFS (69%) rates [ 7 ]. Interestingly, the relapse-free survival curve plateaued after 1 year, suggesting that consolidative HDC/ASCT achieved a durable treatment response. The major cause of transplantation failure in our cohort was disease relapse and progression, whereas transplant-related mortality was low. This result was consistent with previous data. A retrospective observational study from the United Kingdom reported outcomes in PCNSL patients receiving consolidative HDC/ASCT. In this cohort, most deaths were also attributed to disease progression (7 of 12, 58.3%), compared with transplant-related mortality (TRM) (4 of 12, 33.3%) [ 17 ]. A prospective cohort study in France evaluated patients receiving upfront HDC/ASCT, where most underwent thiotepa-based conditioning (54% received the TBC regimen). Similarly, 53% of deaths in that study were attributed to disease progression [ 15 ]. Historically, the BEAM regimen was the preferred conditioning regimen for HDC/ASCT in PCNSL patients [ 18 ]. Although associated with low transplantation-related mortality, disease control with BEAM remained suboptimal, likely due to insufficient drug penetration into the CNS [ 19 – 21 ]. Subsequently, thiotepa was introduced; it showed superior CNS penetration, with cerebrospinal fluid concentrations exceeding 80% of serum levels, potentially enhancing anti-tumor efficacy [ 22 ]. Thus, thiotepa-based conditioning regimens were widely adopted to improve disease control. Across studies, CR rates with thiotepa-based conditioning regimens have consistently improved, accompanied by reduced relapse rates [ 13 , 23 , 24 ]. A systematic review and meta-analysis comparing BEAM with thiotepa-based regimens (TT-BCNU, TBC, or TT/Busulfan) demonstrated improved 2-year OS and PFS with thiotepa-based approaches [ 13 ]. Additionally, a retrospective cohort study using data from the Center for International Blood and Marrow Transplant Research registry, comparing TBC, TT-BCNU, and BEAM conditioning groups, showed superior 3-year PFS rates in thiotepa-based cohorts (TBC: 75%; TT-BCNU: 76%) compared to the BEAM cohort (58%) [ 12 ]. However, thiotepa is associated with toxicities, including significant cytopenia with an associated risk of infection [ 12 , 22 ], and neurotoxicity, potentially contributing to higher NRM [ 12 ]. Moreover, data specific to Asian populations remain scarce. A Japanese retrospective study reported 2-year PFS and OS rates of 50% and 76%, respectively, in patients receiving upfront HDC/ASCT as consolidation; 16 of 102 patients received thiotepa-based conditioning regimens demonstrated a lower cumulative incidence of relapse following transplantation [ 16 ]. Notably, our study did not find survival benefit with thiotepa-based conditioning regimens. There was no significant difference in 2-year OS and RFS between the thiotepa and non-thiotepa groups. Comparing patient characteristics between the two conditioning groups ( Supplementary Table 2 ), the non-thiotepa group had relatively younger patients, a lower proportion of males, and a higher proportion of patients achieving CR before HDC/ASCT. The extent to which these differences influenced the outcomes of thiotepa-based conditioning regimens in our cohort remains uncertain. Additionally, in a real-world setting, patients received heterogeneous induction treatments, including local therapies, before HDC/ASCT, which could have affected the outcomes of thiotepa-based regimens. Another factor potentially influencing treatment practices in Taiwan is the availability and regulatory status of thiotepa. Although thiotepa became available via local distributors around 2010, it was not formally approved by the Taiwan Food and Drug Administration until 2022. Before this approval, using thiotepa often required special authorization via a lengthy, months-long application process. This delay may have affected the timing of HDC/ASCT, limiting its feasibility as a frontline consolidation strategy and reducing access to thiotepa-based induction regimens such as MATRix. Consequently, physicians may have chosen alternative conditioning regimens or suboptimal dosing. Among thiotepa-based regimens, TBC is considered more intensive and is associated with lower relapse rates, albeit at the cost of higher infection risk and NRM compared to TT-BCNU [ 15 , 25 , 26 ]. Therefore, TBC is often reserved for younger or fitter patients, whereas TT-BCNU is generally better tolerated by elderly patients [ 17 , 27 ]. In our study, TT-BCNU was used more frequently than TBC, possibly due to its lower TRM despite a higher risk of disease relapse. One of the three patients in our cohort who received the TBC regimen died within one month post-transplantation from cytomegalovirus (CMV) pneumonia with suspected invasive aspergillosis. However, none of these patients in the TBC group experienced disease relapse during follow-up. Current guidelines, including those from the National Comprehensive Cancer Network, suggest that consolidative HDC/ASCT can be considered for patients achieving CR. However, the prognostic relevance of pre-transplant disease status remains debatable. While some studies found no significant association between pre-ASCT remission status and survival outcomes [ 12 , 15 , 28 ], others indicated a potential prognostic impact. A multicenter cohort study in Japan identified non-CR status before HDC/ASCT as an adverse prognostic factor for OS, reporting a hazard ratio of 2.4 in multivariate analysis [ 16 ]. Similarly, a study from Mayo Clinic demonstrated that both PFS and OS differed significantly based on pre-transplant CR and PR status in either BEAM- or thiotepa-based cohorts [ 29 ]. Within the BEAM group, 5 of 6 patients with PR before transplantation developed progressive disease by day 100 post-transplant, indicating poorer disease control in those not achieving CR. In our study, patients with CR or PR showed a trend toward improved 2-year OS and RFS compared to those without remission, although this difference was not statistically significant (p = 0.51) ( Supplementary Fig. 2 ) ( Supplementary Fig. 3 ). However, one of six patients who underwent transplantation without remission still achieved durable survival and remission. Disease relapse, occurring in approximately 25–50% of patients, is frequently associated with a poor prognosis, and effective treatment options remain limited and challenging [ 30 , 31 ]. Chemotherapy re-challenge is commonly considered the initial salvage approach. Additionally, Bruton tyrosine kinase inhibitors, such as tirabrutinib and ibrutinib, with or without chemotherapy, have demonstrated a median PFS of 4–9 months and a median OS exceeding 1 year [ 32 – 35 ]. WBRT is another option, particularly for patients with a poor response to chemotherapy. It reportedly achieves 2-year OS and PFS of approximately 50%, although neurotoxicity has been observed in approximately 19% of patients post-treatment [ 36 ]. Novel agents, including anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel), have shown a 1-year PFS of 43% and a median OS of 21.2 months [ 37 ]. Despite these advances, HDC/ASCT remains a promising salvage option. Previous studies reported 2-year OS and PFS rates of 40–60%, independent of age, with a median OS exceeding 2 years [ 4 , 31 , 38 ]. Interestingly, in our study, the 18 patients who underwent salvage HDC/ASCT showed high 2-year OS and RFS rates, with durable relapse-free survival. The RFS curve plateaued 1 year after HDC/ASCT. These findings indicate that HDC/ASCT remains a viable treatment option even for relapsed/refractory patients. Notably, these results must be interpreted cautiously due to the limited sample size and potential survivorship bias inherent in this retrospective cohort. Our study has several limitations. First, as a retrospective analysis with a small sample size, its findings may be influenced by heterogeneity in induction chemotherapy and subsequent post-transplant treatments. Second, the prognostic significance of key variables, including IELSG score, MSKCC score [ 39 , 40 ], and ECOG performance status, could not be thoroughly evaluated due to missing data. Third, post-transplant tumor response was not evaluated because the clinical application of IPCG response criteria is limited by inconsistent CSF assessments and variable radiological interpretations, particularly in patients who underwent tumor resection. In conclusion, this retrospective multicenter study provides a real-world analysis of HDC/ASCT for Taiwanese patients with PCNSL in both frontline and salvage settings. The findings reaffirm HDC/ASCT as a viable treatment strategy in both frontline and salvage settings, with 2-year OS and RFS rates comparable to those of previous studies. Although thiotepa-based conditioning was not associated with improved survival compared to non-thiotepa regimens in this study, most deaths were attributed to disease relapse or progression. Consequently, large-scale studies are urgently needed to optimize conditioning regimens for better disease control. Although PCNSL remains a challenging hematological malignancy to treat, novel drugs and multidisciplinary approaches offer potential for improved disease control. Among these treatments, HDC/ASCT remains a cornerstone of PCNSL therapy. Declarations Ethics approval: All procedures followed ethical guidelines, including the Declaration of Helsinki. Informed consent was obtained, and all protocols were approved by the IRBs of participating hospitals. Competing Interests and funding: The authors declare no competing financial or non-financial interests related to this work. All authors have no conflicts of interest to disclose. No funding was received to assist with the preparation of this manuscript Data Availability Statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Acknowledgments We would like to express our gratitude to the Taiwan Society of Blood and Marrow Transplantation (TBMT) and the Taiwan Blood and Marrow Transplantation Registry (TBMTR) for their invaluable support in data collection, coordination, and overall contributions to this work. We also extend our thanks to all participating medical centers for their dedication to patient care and for generously providing the necessary data. Author Contributions Po-Tsen Liuand Pei-An Fu contributed to the study design, data collection and analysis and manuscript draft. 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Available at: [ https://doi.org/10.1002/cam4.5607] Schorb E, Finke J, Ferreri AJ, Ihorst G, Mikesch K, Kasenda B, et al. High-dose chemotherapy and autologous stem cell transplant compared with conventional chemotherapy for consolidation in newly diagnosed primary CNS lymphoma—a randomized phase III trial (MATRix). BMC cancer. 2016;16:1-9. Available at: [https://doi.org/10.1186/s12885-016-2311-4] Schorb E, Isbell LK, Kerkhoff A, Mathas S, Braulke F, Egerer G, et al. High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial. The Lancet Haematology. 2024;11(3):e196-e205. Available at: [https://doi.org/10.1016/S2352-3026(23)00371-X] Kondo E. Primary central nervous system lymphoma: advances in treatment strategies. [Rinsho Ketsueki] The Japanese Journal of Clinical Hematology. 2020;61(5):510-9. Available at: [https://doi.org/10.11406/rinketsu.61.510 ] Scordo M, Wang TP, Ahn KW, Chen Y, Ahmed S, Awan FT, et al. Outcomes associated with thiotepa-based conditioning in patients with primary central nervous system lymphoma after autologous hematopoietic cell transplant. JAMA oncology. 2021;7(7):993-1003. Available at: [ https://doi.org/10.1001/jamaoncol.2021.1074] Alnahhas I, Jawish M, Alsawas M, Zukas A, Prokop L, Murad MH, et al. Autologous stem-cell transplantation for primary central nervous system lymphoma: systematic review and meta-analysis. Clinical Lymphoma Myeloma and Leukemia. 2019;19(3):e129-e41. Available at: [https://doi.org/10.1016/j.clml.2018.11.018] Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. Journal of clinical oncology. 2005;23(22):5034-43. Available at: [https://doi.org/10.1200/JCO.2005.13.524] Schenone L, Houillier C, Tanguy ML, Choquet S, Agbetiafa K, Ghesquières H, et al. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network. Bone marrow transplantation. 2022;57(6):966-74. Available at: [https://doi.org/10.1038/s41409-022-01648-z] Kondo E, Ikeda T, Izutsu K, Chihara D, Shimizu-Koresawa R, Fujii N, et al. High-dose chemotherapy with autologous stem cell transplantation in primary central nervous system lymphoma: data from the Japan Society for Hematopoietic Cell Transplantation Registry. Biology of Blood and Marrow Transplantation. 2019;25(5):899-905. Available at: [https://doi.org/10.1016/j.bbmt.2019.01.020] Kassam S, Chernucha E, O’Neill A, Hemmaway C, Cummins T, Montoto S, et al. High-dose chemotherapy and autologous stem cell transplantation for primary central nervous system lymphoma: a multi-centre retrospective analysis from the United Kingdom. Bone marrow transplantation. 2017;52(9):1268-72. Available at: [https://doi.org/10.1038/bmt.2017.101] Chen Y-B, Lane AA, Logan BR, Zhu X, Akpek G, Aljurf MD, et al. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation. 2015;21(6):1046-53. Available at: [https://doi.org/10.1016/j.bbmt.2015.02.005] Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, et al. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. Journal of clinical oncology. 2003;21(22):4151-6. Available at: [https://doi.org/10.1200/JCO.2003.05.024] Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, et al. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone marrow transplantation. 2006;38(6):417-20. Available at: [https://doi.org/10.1038/sj.bmt.1705452] Steffanoni S, Calimeri T, Marktel S, Nitti R, Foppoli M, Ferreri AJ. Diagnosis and treatment using autologous stem-cell transplantation in primary central nervous system lymphoma: a systematic review. Cancers. 2023;15(2):526. Available at: [https://doi.org/10.3390/cancers15020526] Ferreri AJ, Illerhaus G. The role of autologous stem cell transplantation in primary central nervous system lymphoma. Blood, The Journal of the American Society of Hematology. 2016;127(13):1642-9. Available at: [https://doi.org/10.1182/blood-2015-10-636340] Illerhaus G, Müller F, Feuerhake F, Schäfer A-O, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008;93(1):147-8. Available at: [https://doi.org/10.3324/haematol.11771] Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, et al. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood, The Journal of the American Society of Hematology. 2015;125(9):1403-10. Available at: [https://doi.org/10.1182/blood-2014-10-604561] Delphine L, Pierre-Edouard D, Bruno R, Magalie J, Patrick V, Jean-Pierre M, et al. Thiotepa, busulfan, cyclophosphamide: effective but toxic conditioning regimen prior to autologous hematopoietic stem cell transplantation in central nervous system lymphoma. Medical Sciences. 2023;11(1):14. Available at: [https://doi.org/10.3390/medsci11010014] Scordo M, Bhatt V, Hsu M, Omuro AM, Matasar MJ, DeAngelis LM, et al. A comprehensive assessment of toxicities in patients with central nervous system lymphoma undergoing autologous stem cell transplantation using thiotepa, busulfan, and cyclophosphamide conditioning. Biology of Blood and Marrow Transplantation. 2017;23(1):38-43. Available at: [ https://doi.org/10.1016/j.bbmt.2016.09.024] Akhtar OS, Arshad S, Lian Q, Ahn KW, D'Souza A, Dhakal B, et al. Comparison of Thiotepa-based Conditioning Regimens for Older Adults with Primary Diffuse Large B-cell Lymphoma of the Central Nervous System Undergoing Autologous Hematopoietic Cell Transplantation. Transplantation and Cellular Therapy. 2024;30(12):1191. e1-. e8. Available at: [https://doi.org/10.1016/j.jtct.2024.09.015] Van Der Meulen M, Postma AA, Smits M, Bakunina K, Minnema MC, Seute T, et al. Extent of radiological response does not reflect survival in primary central nervous system lymphoma. Neuro-oncology advances. 2021;3(1):vdab007. Available at: [ https://doi.org/10.1093/noajnl/vdab007 ] Khurana A, Micallef IN, LaPlant BR, O’Neill BP, Habermann TM, Ansell SM, et al. Outcomes of autologous stem cell transplant consolidation in primary central nervous system lymphoma: A Mayo clinic experience. Biology of Blood and Marrow Transplantation. 2020;26(12):2217-22. Available at: [ https://doi.org/10.1016/j.bbmt.2020.08.012] Chuang CH, Kuo MC, Chang H, Wu JH, Hung YS, Ou CW, et al. Different patterns of failure in two treatment regimens for primary central nervous system lymphoma, a retrospective analysis of 124 cases in Taiwan. Clin Exp Med. 2023;23(8):5327-36. Available at: [https://doi.org/10.1007/s10238-023-01182-2] Pellonperä E, Puhakka I, Kuitunen H, Rönkä A, Sunela K, Kuusisto ME, et al. Favourable Outcome of Relapsed PCNSL Among Transplant Eligble Patients. European Journal of Haematology. 2025. Available at: [https://doi.org/10.1111/ejh.14382] Yonezawa H, Narita Y, Nagane M, Mishima K, Terui Y, Arakawa Y, et al. Three-year follow-up analysis of phase 1/2 study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma. Neuro-Oncology Advances. 2024;6(1):vdae037. Available at: [https://doi.org/10.1093/noajnl/vdae037] Liao C-K, Liu C-J, Tan T-D, Wang M-C, Hsu Y-T, Liu H-L, et al. Real World Evidence of Tirabrutinib As a Salvage Treatment in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma in Taiwan: A Multicenter Study. Blood. 2024;144:5137. Available at: [https://doi.org/10.1182/blood-2024-201386] Narita Y, Nagane M, Mishima K, Terui Y, Arakawa Y, Yonezawa H, et al. Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. Neuro Oncol. 2021;23(1):122-33. Available at: [ https://doi.org/10.1093/neuonc/noaa145] Lauer EM, Waterhouse M, Braig M, Mutter J, Bleul S, Duque-Afonso J, et al. Ibrutinib in patients with relapsed/refractory central nervous system lymphoma: A retrospective single-centre analysis. Br J Haematol. 2020;190(2):e110-e4. Available at: [https://doi.org/10.1111/bjh.16759] Volpini ME, Song J, Samant R, MacDonald D, Nair VJ. Cranial Radiation Therapy as Salvage in the Treatment of Relapsed Primary CNS Lymphoma. Current Oncology. 2022;29(11):8160-70. Available at: [https://doi.org/10.3390/curroncol29110644] Choquet S, Soussain C, Azar N, Morel V, Metz C, Ursu R, et al. CAR T‐cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real‐life results of the LOC network. American Journal of Hematology. 2024;99(7):1240-9. Available at: [https://doi.org/10.1002/ajh.27316] Pérol L, Grenier A, Soussain C, Hoang Xuan K, Boussen I, Baron M, et al. ICE polychemotherapy is an efficient salvage treatment in relapsed/refractory primary central nervous system lymphoma. Blood Advances. 2025:bloodadvances. 2024014373. Available at: [https://doi.org/10.1182/bloodadvances.2024014373] Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. Journal of Clinical Oncology. 2006;24(36):5711-5. Available at: [https://doi.org/10.1200/JCO.2006.08.294] Ferreri AJ, Blay J-Y, Reni M, Pasini F, Spina M, Ambrosetti A, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. Journal of Clinical Oncology. 2003;21(2):266-72. Available at: [https://doi.org/10.1200/JCO.2003.09.139] 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-6846411","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471400281,"identity":"64e43cee-2ab3-44f3-a839-4f6be88937f9","order_by":0,"name":"Po-Tsen Liu","email":"","orcid":"","institution":"National Cheng Kung University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Po-Tsen","middleName":"","lastName":"Liu","suffix":""},{"id":471400282,"identity":"363dccb4-9f9f-4f4d-8eac-603c1e3aa661","order_by":1,"name":"Pei-An Fu","email":"","orcid":"","institution":"National Cheng Kung University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pei-An","middleName":"","lastName":"Fu","suffix":""},{"id":471400283,"identity":"7eb5ff54-5e78-4b72-bf71-b64a742f70ac","order_by":2,"name":"Ming Yao","email":"","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Yao","suffix":""},{"id":471400284,"identity":"47c5f6f5-c9a4-4c6e-99ad-b09dbf8cf30c","order_by":3,"name":"Bor-Sheng Ko","email":"","orcid":"","institution":"National Taiwan University Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Bor-Sheng","middleName":"","lastName":"Ko","suffix":""},{"id":471400285,"identity":"8cf860e6-7952-4a92-9757-c6317d1957d2","order_by":4,"name":"Liang-Tsai Hsiao","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Liang-Tsai","middleName":"","lastName":"Hsiao","suffix":""},{"id":471400286,"identity":"65b21ab4-c763-4a85-9db8-c66b3ed42269","order_by":5,"name":"Chia-Jen Liu","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chia-Jen","middleName":"","lastName":"Liu","suffix":""},{"id":471400287,"identity":"27f9a03b-3a22-4735-af64-9672dd8e8eef","order_by":6,"name":"Tsai-Yun Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYPACGwYGZuYGICMBxDPAq5YHQqUBtTAia0kgqOUwEBOrxZ699+HDHzXno/nbGRuYC2rSEhvYm7dJMP44jNsWnuPGxjzHbufOOAzUMuNYTmIDz7EyCYYEPFok0tikGdhu5zaAtPA2VCQ2SOSYAbXcxq1F/hn7zx//zuXOh2uRf0NAiwQbGwNv24HcDRAtQIdJ8BDQciaNWZq3Lzl3I1DLYZ5jacZtPGnFFglp/3FqYW8/xvjxxze73HnnDx98zFOTLNvPfnjjjQ82aTi1oIADIIINRCQQp2EUjIJRMApGAQ4AALqZT+PKXcuqAAAAAElFTkSuQmCC","orcid":"","institution":"National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":true,"prefix":"","firstName":"Tsai-Yun","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-06-08 08:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6846411/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6846411/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84780703,"identity":"6639b99a-8420-4bff-845a-12e6939f7439","added_by":"auto","created_at":"2025-06-17 09:27:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":67960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival outcomes of frontline HDC/ASCT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaplan–Meier survival plots showed overall survival (a) and relapse-free survival (b) from transplantation. The 2- and 3-year overall survival rates were 68.3% and 58.5%, respectively; relapse-free survival rates were 58.8% and 53.4%, respectively\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6846411/v1/36eb9875719c82a9f00bd13a.png"},{"id":84780706,"identity":"fbed11a2-90c3-4ef4-a022-0c14e08df253","added_by":"auto","created_at":"2025-06-17 09:27:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84951,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival outcomes by conditioning regimen in frontline HDC/ASCT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaplan–Meier survival plots showed OS (a) and RFS (b) from transplantation comparing thiotepa-based and non-thiotepa-based conditioning regimens. No significant differences in OS or RFS were observed between the two groups\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6846411/v1/7904b0a1efa2ce5fdd5c2156.png"},{"id":84780708,"identity":"52e2f0de-3072-4ff4-8e73-abe7ba9b4e0a","added_by":"auto","created_at":"2025-06-17 09:27:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":65522,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival outcomes of salvage HDC/ASCT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaplan–Meier survival plots showed OS (a) and RFS (b). The 2-year OS rate was 69.8%, and RFS rate was 58.4%\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6846411/v1/3648d0af57db7258582a9f48.png"},{"id":87489041,"identity":"7006e258-36b2-46e7-87a8-094fadb9bc4a","added_by":"auto","created_at":"2025-07-24 11:31:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1047109,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6846411/v1/67276431-63a5-4f7c-af39-71a984ddbafe.pdf"},{"id":84780713,"identity":"5cef1b74-7c36-4692-9cc5-fcf7a81453d5","added_by":"auto","created_at":"2025-06-17 09:27:16","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":12752236,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-6846411/v1/e837cea6435d243399cf5c12.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Real-world analysis of autologous stem cell transplantation in primary central nervous system lymphoma using Taiwan Blood and Marrow Transplantation Registry (TBMTR)","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary central nervous system lymphoma (PCNSL) is a rare, highly aggressive form of extranodal non-Hodgkin lymphoma confined to the central nervous system (CNS), including the brain, spinal cord, meninges, and vitreoretinal region [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The disease poses significant clinical challenges due to its unique neuroanatomical localization, aggressive progression, high relapse rates, and treatment-associated complications. The standard induction regimen for PCNSL typically includes high-dose methotrexate-based chemotherapy, followed by consolidation with additional chemotherapy, whole-brain radiotherapy (WBRT), or high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile HDC/ASCT was initially used as salvage therapy for relapsed or refractory PCNSL [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], it is now also incorporated as a consolidation option in frontline treatment protocols. Compared with WBRT, which is associated with significant neurocognitive decline, HDC/ASCT offers a less neurotoxic alternative with promising long-term outcomes [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Randomized controlled trials support this therapeutic approach, demonstrating extended progression-free survival (PFS) in newly diagnosed patients who undergo HDC/ASCT as consolidation therapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, real-world evidence remains scarce, especially in Asia, and the overall survival (OS) benefit of frontline HDC/ASCT remains controversial.\u003c/p\u003e \u003cp\u003eMoreover, the conditioning regimen used during transplantation affects outcomes. Thiotepa, an alkylating agent that effectively penetrates the blood-brain barrier, was introduced for treating PCNSL and subsequently incorporated into HDC/ASCT conditioning regimens [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Observational cohort studies suggest that thiotepa-based regimens may improve survival despite their association with higher toxicity and increased non-relapse mortality (NRM), particularly with combinations such as thiotepa, busulfan, and cyclophosphamide (TBC) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Limited access to thiotepa in East Asia, including Taiwan, has restricted its clinical use. This limitation may influence real-world outcomes compared with those from prospective trials, underscoring the need for further investigation.\u003c/p\u003e \u003cp\u003eTo investigate the outcomes and benefits of consolidative autologous transplantation following induction chemotherapy, and to evaluate the impact of conditioning regimens during the transplantation, we retrospectively analyzed data from the Taiwan Blood and Marrow Transplantation Registry (TBMTR) cohort.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData acquisition\u003c/h2\u003e \u003cp\u003eThis retrospective observational study used data from the TBMTR. Seventeen hospitals participating in the Taiwan Society of Blood and Marrow Transplantation contributed data to the TBMTR.\u003c/p\u003e \u003cp\u003ePatients registered in the TBMTR who underwent HDC/ASCT between January 2012 and December 2022 were included. Individuals who received allogeneic HDC/ASCT were excluded. Relevant variables recorded in the TBMTR included age, sex, pre-HDC/ASCT disease status, induction therapies, conditioning regimens, and salvage therapies.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient Classification and Outcome Assessment\u003c/h3\u003e\n\u003cp\u003eEnrolled patients were categorized into two groups: the frontline HDC/ASCT group (those without reported relapse before transplantation) and the salvage HDC/ASCT group (patients with reported relapse before transplantation).\u003c/p\u003e \u003cp\u003eTreatment response before HDC/ASCT was assessed by local neuroradiologists at individual centers using contrast-enhanced magnetic resonance imaging. Evaluations followed the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria for PCNSL, ensuring consistency in treatment outcome assessments. Notably, ophthalmologic and cerebrospinal fluid (CSF) assessments were not routinely performed. Final response interpretations and treatment decisions were made by local hematologists [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe study aimed to evaluate OS and relapse-free survival (RFS) in PCNSL patients undergoing frontline or salvage HDC/ASCT. OS was defined as the time from transplantation to death from any cause or last follow-up, whereas RFS was measured from transplantation to disease relapse, death, or last follow-up.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eOS and RFS probabilities were estimated using the Kaplan\u0026ndash;Meier method. All statistical analyses and graphical representations were performed using RStudio software (version 2024.12.0\u0026thinsp;+\u0026thinsp;467). A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eThis study analyzed data from 65 PCNSL patients in the TBMTR between 2012 and 2022. Forty-seven patients (73.2%) were classified into the frontline HDC/ASCT group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and the remaining 18 (26.8%) into the salvage HDC/ASCT group. The median age of all patients was 57 years, and the oldest patient was 78. The median follow-up for all patients was 34.6 months: 19.9 months in the frontline HDC/ASCT group, and 63.2 months in the salvage group. The median time from initial diagnosis to HDC/ASCT was 6.7 months in the frontline group, whereas it was significantly longer (32.4 months) for the salvage group. Fourteen patients (21.5%) were hepatitis B virus carriers. Only one patient (1.5%) had human immunodeficiency virus infection who was included in the frontline group. Elevated lactate dehydrogenase (LDH) levels before HDC/ASCT were observed in 20 patients (30.8%), predominantly in the frontline group. Twenty percent of patients had received radiotherapy before HDC/ASCT, with a higher percentage (38.9%) in the salvage group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; baseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrontline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSalvage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (73.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (26.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (38\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (40\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (38\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, male, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (56.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (51.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (72.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up time, months, median (Range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.6 (5.8-156.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.9 (5.8-150.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.2 (36.1-156.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2012\u0026ndash;2017, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (34.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (72.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u0026ndash;2022, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (66.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian time from diagnosis to HDC/ASCT, months (Range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.1 (3.6\u0026ndash;65.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7 (3.6\u0026ndash;49.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.4 (10.1\u0026ndash;65.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV carrier, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResolved HBV, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV status, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated LDH, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy exposure before HDC/ASCT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eChemotherapy regimens before\u003c/p\u003e \u003cp\u003eHDC/ASCT, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (78.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegimens of induction chemotherapy, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDMTX based\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYVE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemozolomide/R/Ara-C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR-MATRix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrathecal therapy (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (66.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBest response before HDC/ASCT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (33.3)\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\u003e30 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;PR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConditioning regimen, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThiotepa-based\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (61.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT-BCNU +/- R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (86.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (71.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBC +/- R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThiotepa total dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10mg/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20mg/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-thiotepa based\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (61.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBEAM +/- R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (82.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (72.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeEAM +/- R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (18.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAra-C: cytarabine, BeEAM: bendamustine, etoposide, cytarabine, melphalan, BEAM: carmustine, etoposide, cytarabine, melphalan, CR: complete remission, CYVE: Cytarabine and etoposide, HBV: hepatitis B virus, HDC/ASCT: high-dose chemotherapy with autologous stem-cell transplant, HDMTX: High-dose methotrexate, HIV: human immunodeficiency virus, LDH: lactate dehydrogenase, PR: partial remission, R: rituximab, R-MATRix: methotrexate, cytarabine, thiotepa and rituximab, TBC: thiotepa, busulfan, and cyclophosphamide, TT-BCNU: thiotepa, carmustine\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e4 patients at 250 mg/m\u0026sup2; for 3 days in TBC regimen, while 1 had an unknown dose.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the frontline group, 37 patients received high-dose methotrexate (HDMTX)-based regimens, whereas the remaining 10 received local therapies or immunotherapy without systemic chemotherapy before consolidative HDC/ASCT. Patients in the frontline group treated with HDMTX-based regimens may have received alternating R-MATRix, cytarabine, or addition of temozolomide. In the salvage group, most patients received two or more chemotherapy lines before HDC/ASCT. Chemotherapy regimens in the salvage group were diverse. Intrathecal chemotherapy was administered to 31 patients (66.0%) in the frontline group and 8 (44.4%) in the salvage group. Before transplantation, 23 patients (48.9%) in the frontline group and 6 (33.3%) in the salvage group achieved complete remission (CR). Twenty-two patients (46.8%) in the frontline group and 8 (44.4%) in the salvage group had partial remission (PR) before HDC/ASCT. Two (4.3%) frontline patients and 4 (22.2%) salvage patients underwent HDC/ASCT without achieving remission.\u003c/p\u003e \u003cp\u003eOver half the patients (61.7%) in the frontline group received thiotepa-based conditioning regimens for HDC/ASCT, whereas only 7 (38.9%) in the salvage group received such regimens. Thiotepa-based regimens mainly consisted of TT-BCNU (thiotepa, carmustine [BCNU]) or TBC (thiotepa, busulfan, and cyclophosphamide), with or without rituximab. The non-thiotepa group primarily received the BEAM regimen (BCNU, etoposide, cytarabine, and melphalan), with or without rituximab. Thiotepa was predominantly administered at a total dose of 10 mg/kg over the conditioning course.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSurvival Outcomes in the Frontline HDC/ASCT Group\u003c/h2\u003e \u003cp\u003eFor the frontline HDC/ASCT group, 2- and 3-year OS rates were 68.3% (95% CI, 54.5\u0026ndash;85.6) and 58.5% (95% CI, 42.8\u0026ndash;79.9), respectively. The 2- and 3-year RFS rates were 58.8% (95% CI, 45.3\u0026ndash;76.3) and 53.4% (95% CI, 38.8\u0026ndash;73.7), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor patients in the frontline HDC/ASCT group receiving thiotepa-based conditioning regimens, 2- and 3-year OS rates were both 58.3% (95% CI, 37.2\u0026ndash;91.2). In the non-thiotepa group, the 2-year OS rate was 76.6% (95% CI, 58.8\u0026ndash;99.7) and the 3-year OS rate was 62.7% (95% CI, 42.7\u0026ndash;92.0) (p\u0026thinsp;=\u0026thinsp;0.84) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Moreover, for the thiotepa-based conditioning group, the 2- and 3-year RFS rates were both 58.0% (95% CI, 40.9\u0026ndash;82.2), whereas for the non-thiotepa group, these rates were 58.8% (95% CI, 39.2\u0026ndash;88.3) and 51.5% (95% CI, 31.8\u0026ndash;83.5), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb); this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.87).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurvival Outcomes in the Salvage HDC/ASCT Group\u003c/h3\u003e\n\u003cp\u003eIn the salvage HDC/ASCT group, the 2- and 3-year OS rates were both 69.8% (95% CI, 48.4\u0026ndash;100). Additionally, the 2- and 3-year RFS rates were both 58.4% (95% CI, 39.0\u0026ndash;87.7) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eMortality and Infection-Related Complications in HDC/ASCT Patients\u003c/h3\u003e\n\u003cp\u003eAll patients achieved engraftment, with a comparable median engraftment time of 9 days in both conditioning groups (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e). Among the 65 patients who underwent HDC/ASCT, 20 (30.8%) died during follow-up (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Disease progression was the primary cause (13 deaths), followed by infection (5 deaths). Sixteen deaths occurred in the frontline HDC/ASCT group: 8 in the thiotepa-based subgroup and 8 in the non-thiotepa group (\u003cb\u003eSupplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/b\u003e). Of these 8 deaths in the thiotepa-based subgroup, disease relapse or progression was the leading cause (5 patients), followed by infection (3 patients). During follow-up, 20 of the 65 patients experienced disease relapse: 13 in the frontline group and 7 in the salvage group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eCause of mortality in autologous HDC/ASCT and salvage chemotherapy following relapse\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrontline, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSalvage, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality,\u0026nbsp;n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (34.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMajor cause of mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease-related\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (75.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelapse, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalvage regimen,\u0026nbsp;n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDMTX based\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYVE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRituximab/Lenalidomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther or unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCYVE: Cytarabine, etoposide, HD C/ASCT: high-dose chemotherapy with autologous stem-cell transplant, HDMTX: High-dose methotrexate, ICE: ifosfamide, carboplatin and etoposide\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eInfections were a major post-HDC/ASCT non-relapse event, particularly within the first 100 days. Among all 65 patients receiving HDC/ASCT, 25 (38.5%) developed infections (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), with a higher incidence in the non-thiotepa group. Thirty-nine infection episodes were reported. Pneumonia was the most frequent infection in both conditioning groups, with bacterial pathogens being the predominant cause.\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\u003ePost-transplant infection within 100 days\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eThiotepa\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNon-thiotepa\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e25 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (32.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (55.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal events, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e14 (35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (46.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary tract, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e5 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntra-abdominal, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRBSI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e5 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSoft tissue, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e5 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMV viremia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther/unknown, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogens, events (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e22 (56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (69.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e7 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFungus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e7 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCRBSI: Catheter-related bloodstream infection\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective observational study is Taiwan\u0026rsquo;s first multicenter analysis of autologous HDC/ASCT outcomes in PCNSL patients, focusing on the role of frontline HDC/ASCT and conditioning regimens. Our findings reaffirm HDC/ASCT as a feasible consolidation strategy, with 2-year OS and RFS rates that are consistent with previous international data from trials such as PRECIS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and IELSG 32[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and other nationwide cohort studies [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The PRECIS study [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] compared HDC/ASCT to WBRT and showed a 2-year PFS benefit of 87% in the transplant group, although it focused on younger patients (aged 18\u0026ndash;60). Similarly, the IELSG 32 study reported comparable 2-year OS (71%) and PFS (69%) rates [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Interestingly, the relapse-free survival curve plateaued after 1 year, suggesting that consolidative HDC/ASCT achieved a durable treatment response. The major cause of transplantation failure in our cohort was disease relapse and progression, whereas transplant-related mortality was low. This result was consistent with previous data. A retrospective observational study from the United Kingdom reported outcomes in PCNSL patients receiving consolidative HDC/ASCT. In this cohort, most deaths were also attributed to disease progression (7 of 12, 58.3%), compared with transplant-related mortality (TRM) (4 of 12, 33.3%) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A prospective cohort study in France evaluated patients receiving upfront HDC/ASCT, where most underwent thiotepa-based conditioning (54% received the TBC regimen). Similarly, 53% of deaths in that study were attributed to disease progression [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistorically, the BEAM regimen was the preferred conditioning regimen for HDC/ASCT in PCNSL patients [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Although associated with low transplantation-related mortality, disease control with BEAM remained suboptimal, likely due to insufficient drug penetration into the CNS [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Subsequently, thiotepa was introduced; it showed superior CNS penetration, with cerebrospinal fluid concentrations exceeding 80% of serum levels, potentially enhancing anti-tumor efficacy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Thus, thiotepa-based conditioning regimens were widely adopted to improve disease control. Across studies, CR rates with thiotepa-based conditioning regimens have consistently improved, accompanied by reduced relapse rates [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A systematic review and meta-analysis comparing BEAM with thiotepa-based regimens (TT-BCNU, TBC, or TT/Busulfan) demonstrated improved 2-year OS and PFS with thiotepa-based approaches [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, a retrospective cohort study using data from the Center for International Blood and Marrow Transplant Research registry, comparing TBC, TT-BCNU, and BEAM conditioning groups, showed superior 3-year PFS rates in thiotepa-based cohorts (TBC: 75%; TT-BCNU: 76%) compared to the BEAM cohort (58%) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, thiotepa is associated with toxicities, including significant cytopenia with an associated risk of infection [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and neurotoxicity, potentially contributing to higher NRM [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, data specific to Asian populations remain scarce. A Japanese retrospective study reported 2-year PFS and OS rates of 50% and 76%, respectively, in patients receiving upfront HDC/ASCT as consolidation; 16 of 102 patients received thiotepa-based conditioning regimens demonstrated a lower cumulative incidence of relapse following transplantation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, our study did not find survival benefit with thiotepa-based conditioning regimens. There was no significant difference in 2-year OS and RFS between the thiotepa and non-thiotepa groups. Comparing patient characteristics between the two conditioning groups (\u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e), the non-thiotepa group had relatively younger patients, a lower proportion of males, and a higher proportion of patients achieving CR before HDC/ASCT. The extent to which these differences influenced the outcomes of thiotepa-based conditioning regimens in our cohort remains uncertain. Additionally, in a real-world setting, patients received heterogeneous induction treatments, including local therapies, before HDC/ASCT, which could have affected the outcomes of thiotepa-based regimens. Another factor potentially influencing treatment practices in Taiwan is the availability and regulatory status of thiotepa. Although thiotepa became available via local distributors around 2010, it was not formally approved by the Taiwan Food and Drug Administration until 2022. Before this approval, using thiotepa often required special authorization via a lengthy, months-long application process. This delay may have affected the timing of HDC/ASCT, limiting its feasibility as a frontline consolidation strategy and reducing access to thiotepa-based induction regimens such as MATRix. Consequently, physicians may have chosen alternative conditioning regimens or suboptimal dosing.\u003c/p\u003e \u003cp\u003eAmong thiotepa-based regimens, TBC is considered more intensive and is associated with lower relapse rates, albeit at the cost of higher infection risk and NRM compared to TT-BCNU [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Therefore, TBC is often reserved for younger or fitter patients, whereas TT-BCNU is generally better tolerated by elderly patients [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In our study, TT-BCNU was used more frequently than TBC, possibly due to its lower TRM despite a higher risk of disease relapse. One of the three patients in our cohort who received the TBC regimen died within one month post-transplantation from cytomegalovirus (CMV) pneumonia with suspected invasive aspergillosis. However, none of these patients in the TBC group experienced disease relapse during follow-up.\u003c/p\u003e \u003cp\u003e Current guidelines, including those from the National Comprehensive Cancer Network, suggest that consolidative HDC/ASCT can be considered for patients achieving CR. However, the prognostic relevance of pre-transplant disease status remains debatable. While some studies found no significant association between pre-ASCT remission status and survival outcomes [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], others indicated a potential prognostic impact. A multicenter cohort study in Japan identified non-CR status before HDC/ASCT as an adverse prognostic factor for OS, reporting a hazard ratio of 2.4 in multivariate analysis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similarly, a study from Mayo Clinic demonstrated that both PFS and OS differed significantly based on pre-transplant CR and PR status in either BEAM- or thiotepa-based cohorts [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Within the BEAM group, 5 of 6 patients with PR before transplantation developed progressive disease by day 100 post-transplant, indicating poorer disease control in those not achieving CR. In our study, patients with CR or PR showed a trend toward improved 2-year OS and RFS compared to those without remission, although this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.51) (\u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e) (\u003cb\u003eSupplementary Fig.\u0026nbsp;3\u003c/b\u003e). However, one of six patients who underwent transplantation without remission still achieved durable survival and remission.\u003c/p\u003e \u003cp\u003eDisease relapse, occurring in approximately 25\u0026ndash;50% of patients, is frequently associated with a poor prognosis, and effective treatment options remain limited and challenging [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Chemotherapy re-challenge is commonly considered the initial salvage approach. Additionally, Bruton tyrosine kinase inhibitors, such as tirabrutinib and ibrutinib, with or without chemotherapy, have demonstrated a median PFS of 4\u0026ndash;9 months and a median OS exceeding 1 year [\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. WBRT is another option, particularly for patients with a poor response to chemotherapy. It reportedly achieves 2-year OS and PFS of approximately 50%, although neurotoxicity has been observed in approximately 19% of patients post-treatment [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Novel agents, including anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel), have shown a 1-year PFS of 43% and a median OS of 21.2 months [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Despite these advances, HDC/ASCT remains a promising salvage option. Previous studies reported 2-year OS and PFS rates of 40\u0026ndash;60%, independent of age, with a median OS exceeding 2 years [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Interestingly, in our study, the 18 patients who underwent salvage HDC/ASCT showed high 2-year OS and RFS rates, with durable relapse-free survival. The RFS curve plateaued 1 year after HDC/ASCT. These findings indicate that HDC/ASCT remains a viable treatment option even for relapsed/refractory patients. Notably, these results must be interpreted cautiously due to the limited sample size and potential survivorship bias inherent in this retrospective cohort.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, as a retrospective analysis with a small sample size, its findings may be influenced by heterogeneity in induction chemotherapy and subsequent post-transplant treatments. Second, the prognostic significance of key variables, including IELSG score, MSKCC score [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], and ECOG performance status, could not be thoroughly evaluated due to missing data. Third, post-transplant tumor response was not evaluated because the clinical application of IPCG response criteria is limited by inconsistent CSF assessments and variable radiological interpretations, particularly in patients who underwent tumor resection.\u003c/p\u003e \u003cp\u003eIn conclusion, this retrospective multicenter study provides a real-world analysis of HDC/ASCT for Taiwanese patients with PCNSL in both frontline and salvage settings. The findings reaffirm HDC/ASCT as a viable treatment strategy in both frontline and salvage settings, with 2-year OS and RFS rates comparable to those of previous studies. Although thiotepa-based conditioning was not associated with improved survival compared to non-thiotepa regimens in this study, most deaths were attributed to disease relapse or progression. Consequently, large-scale studies are urgently needed to optimize conditioning regimens for better disease control. Although PCNSL remains a challenging hematological malignancy to treat, novel drugs and multidisciplinary approaches offer potential for improved disease control. Among these treatments, HDC/ASCT remains a cornerstone of PCNSL therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures followed ethical guidelines, including the Declaration of Helsinki. Informed consent was obtained, and all protocols were approved by the IRBs of participating hospitals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests and funding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing financial or non-financial interests related to this work. All authors have no conflicts of interest to disclose.\u0026nbsp;No funding was received to assist with the preparation of this manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our gratitude to the Taiwan Society of Blood and Marrow Transplantation (TBMT) and the Taiwan Blood and Marrow Transplantation Registry (TBMTR) for their invaluable support in data collection, coordination, and overall contributions to this work. We also extend our thanks to all participating medical centers for their dedication to patient care and for generously providing the necessary data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePo-Tsen Liuand Pei-An Fu contributed to the study design, data collection and analysis and manuscript draft. Tsai-Yun Chen was responsible for supervising and instructing the work. Ming Yao, Bor-Sheng Ko, Liang-Tsai Hsiaoand\u0026nbsp;Chia-Jen Liu\u0026nbsp;contributed to the data collection.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFerreri AJM, Calimeri T, Cwynarski K, Dietrich J, Grommes C, Hoang-Xuan K, et al. Primary central nervous system lymphoma. Nature Reviews Disease Primers. 2023;9(1):29. Available at: [https://doi.org/10.1038/s41572-023-00439-0]\u003c/li\u003e\n \u003cli\u003eSchaff LR, Grommes C. Primary central nervous system lymphoma. 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Br J Haematol. 2020;190(2):e110-e4. Available at: [https://doi.org/10.1111/bjh.16759]\u003c/li\u003e\n \u003cli\u003eVolpini ME, Song J, Samant R, MacDonald D, Nair VJ. Cranial Radiation Therapy as Salvage in the Treatment of Relapsed Primary CNS Lymphoma. Current Oncology. 2022;29(11):8160-70. Available at: [https://doi.org/10.3390/curroncol29110644]\u003c/li\u003e\n \u003cli\u003eChoquet S, Soussain C, Azar N, Morel V, Metz C, Ursu R, et al. CAR T‐cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real‐life results of the LOC network. American Journal of Hematology. 2024;99(7):1240-9. Available at: [https://doi.org/10.1002/ajh.27316]\u003c/li\u003e\n \u003cli\u003eP\u0026eacute;rol L, Grenier A, Soussain C, Hoang Xuan K, Boussen I, Baron M, et al. ICE polychemotherapy is an efficient salvage treatment in relapsed/refractory primary central nervous system lymphoma. Blood Advances. 2025:bloodadvances. 2024014373. Available at: [https://doi.org/10.1182/bloodadvances.2024014373]\u003c/li\u003e\n \u003cli\u003eAbrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. Journal of Clinical Oncology. 2006;24(36):5711-5. Available at: [https://doi.org/10.1200/JCO.2006.08.294]\u003c/li\u003e\n \u003cli\u003eFerreri AJ, Blay J-Y, Reni M, Pasini F, Spina M, Ambrosetti A, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. Journal of Clinical Oncology. 2003;21(2):266-72. Available at: [https://doi.org/10.1200/JCO.2003.09.139]\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":"non-Hodgkin's lymphoma, primary CNS lymphoma, autologous stem cell transplantation, frontline intensification ","lastPublishedDoi":"10.21203/rs.3.rs-6846411/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6846411/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAlthough high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is an established consolidation strategy for primary central nervous system lymphoma (PCNSL), real-world data remain limited, especially in Asia. This retrospective multicenter study analyzed 65 PCNSL patients from the Taiwan Blood and Marrow Transplantation Registry (TBMTR) who underwent HDC/ASCT between 2012 and 2022. Patients were classified into the frontline (n = 47) and salvage (n = 18) HDC/ASCT groups. The 2-year overall survival (OS) and relapse-free survival (RFS) rates were 68.3% and 58.8% in the frontline group, and 69.8% and 58.4% in the salvage group, respectively. Thiotepa-based regimens showed no survival advantage; the 2-year OS was 58.3% for thiotepa recipients versus 76.6% for non-thiotepa recipients (p = 0.84). This finding may be attributed to limited access to thiotepa and the small number of patients who received thiotepa-based induction chemotherapy. Disease relapse or progression was the primary cause of mortality across all groups, whereas infection or other non-relapse mortality was infrequent. In this study, HDC/ASCT improved OS and RFS for PCNSL patients in both frontline and salvage settings, although the thiotepa-based conditioning regimen showed no survival benefit.\u003c/p\u003e","manuscriptTitle":"Real-world analysis of autologous stem cell transplantation in primary central nervous system lymphoma using Taiwan Blood and Marrow Transplantation Registry (TBMTR)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 09:27:11","doi":"10.21203/rs.3.rs-6846411/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":"0977ae7c-9e90-4cc4-b2c8-b9593e3043d5","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-24T11:23:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 09:27:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6846411","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6846411","identity":"rs-6846411","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}