High-dose Thiotepa, Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplantation as Upfront Consolidation for Systemic Non-Hodgkin Lymphoma With Synchronous Central Nervous System Involvement

Clin Lymphoma Myeloma Leuk. 2017 Dec;17(12):884-888. doi: 10.1016/j.clml.2017.08.100. Epub 2017 Aug 15.

Abstract

Introduction: Synchronous involvement of the central nervous system (CNS) at the diagnosis of systemic non-Hodgkin lymphoma (NHL) is associated with an increased risk for relapse despite complete remission to initial therapy. High-dose chemotherapy with a CNS-directed conditioning regimen followed by autologous stem cell transplantation (ASCT) holds promise as a consolidative approach.

Patients and methods: We conducted a retrospective analysis of all patients with systemic B-cell NHL and synchronous CNS involvement who received upfront consolidation with high-dose chemotherapy with thiotepa, busulfan, cyclophosphamide, and ASCT while in first complete remission between July 2008 and June 2016 at 2 partner academic institutions.

Results: Twenty patients were identified through the transplant database. The median age at diagnosis was 53 years (range, 37-65 years). The majority had diffuse large B-cell lymphoma histology (n = 17; 85%). The sites of CNS involvement were parenchymal (n = 12; 60%) and leptomeningeal disease (n = 9; 45%). All patients received systemic and CNS-directed therapy prior to transplant, with the most common approaches being R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) (n = 13; 65%) and high-dose intravenous methotrexate (n = 16; 80%), respectively. With a median follow up of 4.4 years after ASCT (range, 2 months-8.5 years), the Kaplan-Meier estimates of 4-year progression-free and overall survival were 77% (95% confidence interval, 48%-91%) and 82% (95% confidence interval, 54%-94%), respectively.

Conclusion: CNS-directed high-dose chemotherapy and ASCT provides durable remission for patients with synchronous aggressive lymphoma and should be strongly considered as consolidative therapy for eligible patients with systemic NHL with CNS involvement in first complete remission.

Keywords: Blood brain barrier; Chronic lymphocytic leukemia; Diffuse large B-cell lymphoma; High-dose chemotherapy; Mantle cell lymphoma.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Central Nervous System / pathology*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Middle Aged
  • Remission Induction
  • Retrospective Studies
  • Stem Cell Transplantation / methods*
  • Thiotepa / administration & dosage
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Cyclophosphamide
  • Thiotepa
  • Busulfan