Real-world experiences of CNS-directed chemotherapy followed by autologous stem cell transplantation for secondary CNS involvement in relapsed or refractory diffuse large B-cell lymphoma

Front Oncol. 2023 Jan 19:12:1071281. doi: 10.3389/fonc.2022.1071281. eCollection 2022.

Abstract

Introduction: Secondary central nervous system (CNS) involvement is a rare but fatal event in patients with diffuse large B cell lymphoma (DLBCL). Some studies have suggested autologous stem cell transplantation (ASCT) for patients responding to salvage therapies, although its role is not clear.

Methods: We analyzed DLBCL patients with secondary CNS involvement who received salvage therapies with curative intent and who underwent high-dose chemotherapy followed by ASCT. We analyzed the post-ASCT outcome in terms of CNS and/or systemic relapse and overall survival (OS) according to type of secondary CNS involvement and salvage treatment.

Results: A total of 43 patients who achieved complete or partial response after salvage treatments, mainly high-dose methotrexate (MTX)-containing chemotherapy, was treated with busulphan-thiotepa followed by ASCT between 2009 to 2019. Fifteen patients experienced grade III/IV febrile neutropenia, but all adverse events were manageable. At the median follow-up of 14.7 months after ASCT, 17 patients did not relapse, however, 26 patients had relapsed, comprising isolated CNS relapse (n = 12), systemic relapse (n = 12), and both (n = 2). Patients with systemic relapse had significantly shorter OS than those with isolated CNS relapse (42.7 vs, 11.1 months, p = 0.002). Of the 26 patients who relapsed after ASCT, six patients were rescued by subsequent salvage treatments. Finally, 21 patients were alive at the time of analysis.

Discussion: In conclusion, consolidative ASCT might be beneficial for secondary CNS involvement in relapsed or refractory DLBCL patients if they responded to CNS-directed salvage chemotherapy and were eligible for transplantation.

Keywords: autologous stem cell transplantation; diffuse large B-cell lymphoma; high-dose methotrexate (HD-MTX); salvage treatment; secondary CNS involvement.

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C0999).