Comparison of Thiotepa, Busulfan, and Cyclophosphamide Versus Busulfan and Thiotepa Conditioning Regimens in Autologous Stem Cell Transplantation for Primary CNS Lymphoma: A Multicenter Retrospective Analysis.

Autologous stem cell transplantation (ASCT) with thiotepa-based conditioning has replaced whole-brain radiotherapy as consolidation for primary central nervous system lymphoma (PCNSL), providing improved efficacy and reduced neurotoxicity. However, the optimal thiotepa-containing regimen remains undefined. We retrospectively analyzed patients aged ≤ 60 years who underwent ASCT with thiotepa-busulfan-cyclophosphamide (TBC) or busulfan-thiotepa (BuTT) conditioning after high-dose methotrexate-based induction at two Korean institutions between 2015 and 2023. Propensity score matching (PSM; n = 20 per group) was performed to adjust for baseline differences. Sixty-seven patients were included (TBC, n = 30; BuTT, n = 37). TBC was associated with significantly longer progression-free survival (PFS) from induction (3-year: 89.9% vs. 72.1%, p = 0.034) and from transplantation (89.9% vs. 69.2%, p = 0.032); overall survival did not differ significantly. In multivariable Cox regression adjusted for pre-transplant response and cumulative MTX exposure, BuTT was independently associated with inferior PFS (HR 4.09, 95% CI 1.27-13.18, p = 0.019). After PSM, TBC retained superior PFS (84.7% vs. 73.3%, p = 0.035), with a non-significant trend in Cox analysis (HR 0.22, 95% CI 0.05-1.03, p = 0.054). TBC was associated with delayed engraftment and more grade ≥ 3 non-hematologic toxicities, but no treatment-related mortality occurred. In younger patients with PCNSL, TBC demonstrated a trend toward more durable disease control than BuTT, with manageable toxicity. As the thiotepa dose represents the major distinction between regimens, dose-intensified thiotepa strategies with adjusted partner agents merit further prospective investigation.