Mitoxantrone hydrochloride liposome injection combined with thiotepa-busulfan-fludarabine (MTBF) as conditioning regimen in patients undergoing allogeneic hematopoietic stem cell transplantation for central nervous system leukemia:a single-center ret

Abstract Background：Limited data is available to guide the choice of non-TBI conditioning regimen for patients with central nervous system leukemia (CNSL).Thiotepa- busulfan-fludarabine (TBF) regimen shows promising results in patients with extramedullary leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).In our previous clinical trial showed that mitoxantrone hydrochloride liposome injection combined with thiotepa-busulfan-fludarabine (MTBF) was an effective and safe conditioning regimen for salvage allo-HSCT in refractory or relapsed acute leukemia. Objective: To compare the safety and efficacy of MTBF and TBF as conditioning regimen in CNSL patients undergoing allo-HSCT. Methods: This is a single-center retrospective case-control study（NCT05667402). Data of 21 acute leukemia patients with CNSL admitted to the first affiliated hospital of Xi'an Jiaotong university from Februray 2022 to June 2025 were retrospectively analyzed.A basic characteristic matching analysis of MTBF(n=7) and TBF(n=14) group was conducted at a 1:2 ratio.Adverse effects of conditioning, hematopoietic recovery, acute and chronic graft versus host disease (GVHD),progression free survival (PFS)and overall survival (OS) were compared between two groups.Results: The median age of the patients were 26(15-58)years old,included 9 females and 12 males,6 acute lymphoblastic leukemia and 15 acute myeloid leukemia,3 with matched sibiling donors and 18 with haploidentical related donors.The median follow-up time was 27(1-42) months. All patients had successful hematopoietic recovery, the median time for neutrophil recovery was 10 (9-19) days, the median time for platelet recovery was 12 (9-41) days. The most common adverse reactions of conditioning were nausea,vomiting,diarrhea and oral mucositis.Five patients had grade II-IV acute GVHD and four patients had chronic GVHD.One year PFS and OS were 69.3%±11.9% and 72.1%±10.9% respectively.One year cumulative incidence of relapse was 29.2%.There were no significance differences of adverse reactions,hematopoietic recovery,acute and chronic GVHD between two groups.No one relapsed in MTBF group and six patients relapsed in TBF group.There was a trend of better PFS and OS of MTBF group than that of TBF group. Conclusion: Compared with TBF regimen,MTBF may be a safe and more effective chemotherapy-based conditioning regimen for CNSL patients undergoing allo-HSCT.However, due to the small number of cases and the retrospective nature of the study, it is still necessary to expand the sample size for further prospective research. Keywords: Central nervous system leukemia; Allogeneic hematopoietic stem cell transplantation;MTBF conditioning.