De-escalated Induction Therapy and Thiotepa/Busulfan-based Autologous Stem Cell Transplantation for Primary Central Nervous System Lymphoma

This retrospective study of 71 patients with primary central nervous system lymphoma demonstrates that an abbreviated, reduced-intensity induction regimen followed by thiotepa/busulfan-based ASCT achieves high transplantation rates with low risks of relapse and treatment-related mortality, thereby providing an effective treatment strategy for PCNSL. Background: Thiotepa-based autologous stem cell transplantation (ASCT) improves survival in primary central nervous system lymphoma (PCNSL), but > 30% of patients are unable to undergo ASCT following commonly used intensive induction regimens. Methods: This retrospective population-based study included consecutive patients >= 18 years old with PCNSL who were intended for ASCT in Alberta, Canada between 2011 and 2022. A reduced-intensity induction protocol was further abbreviated in 2018 to decrease toxicity and expediate ASCT by incorporating rituximab, procarbazine, and only 2 doses of high-dose methotrexate and 1 cycle of high-dose cytarabine before consolidation with thiotepa-busulfan conditioning. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method. Results: Among 71 patients with median age 58 years (range 26-72), ASCT was completed in 56 (79%), with the transplantation rate among patients > 60 years old increasing by 30% following the abbreviation of induction therapy. With median follow-up time 3.9 years, 4-year PFS and OS were 69% (95% CI 56%-79%) and 80% (95% CI 67%-88%) for all patients and 75% (95% CI 57%-86%) and 85% (95% CI 68%-93%) for ASCT recipients, respectively. There was 1 death due to treatment-related mortality during induction and none after ASCT, including among 17 transplanted patients > 60 years old. Conclusion: An abbreviated induction regimen followed by thiotepa-busulfan-based ASCT achieves high transplantation rates with low risks of relapse and treatment-related mortality, thereby providing an effective treatment strategy for PCNSL.