Autologous stem cell transplantation with thiotepa, busulfan, and cyclophosphamide conditioning in patients with central nervous system lymphoma: a phase II study.

The prognosis of central nervous system lymphoma (CNSL) remains poor, and attempts have been made to improve outcomes through autologous stem cell transplantation (ASCT) with thiotepa-based conditioning. We aimed to assess the outcomes of thiotepa/busulfan/cyclophosphamide (TBC) followed by ASCT in CNSL. An investigator-initiated, single-arm, phase II trial was conducted to evaluate the efficacy and safety of TBC/ASCT (NCT06625359). The conditioning dose was adjusted based on age and performance status (9-day or 8-day regimen). As this trial was terminated early after enrolling 17 patients, a retrospective cohort of CNSL treated with the same protocol was included. In total, 44 patients were included in the study and classified into 8-day and 9-day groups according to the TBC regimen received. In total, 25 patients (56.8%) had primary CNSL, and 19 patients (43.2%) received the 9-day regimens. Following ASCT, 33 patients (75.0%) achieved an objective response (32 complete response and 1 partial response). The 3-year progression-free survival (46.5% vs. 52.6%, P = 0.49) and overall survival (60.5% vs. 73.7%, P = 0.77) for 8-day and 9-day groups were comparable. The 1-year cumulative incidence of non-relapse mortality in the 8-day group showed a trend toward decrease compared to that in the 9-day group (4.6% vs. 21.1%, P = 0.073). Our study demonstrates the efficacy of TBC/ASCT in CNSL in the Asian population. The conventional busulfan dose (9-day regimen) may be associated with higher toxicity, suggesting the potential need for a modified TBC regimen in Asian populations. Further studies are needed to identify the optimal thiotepa-based conditioning in CNSL.