Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen

Clin Lymphoma Myeloma Leuk. 2020 Jul;20(7):468-479. doi: 10.1016/j.clml.2020.02.009. Epub 2020 Feb 20.

Abstract

Background: High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.

Patients and methods: A retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).

Results: The 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.

Conclusion: HDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.

Keywords: ASCT; Non-Hodgkin lymphoma; PCNSL; Relapse; SCNL.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / pharmacology
  • Busulfan / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / mortality
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / mortality
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thiotepa / pharmacology
  • Thiotepa / therapeutic use*

Substances

  • Cyclophosphamide
  • Thiotepa
  • Busulfan