High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma

Abstract

Summary:Treatment of primary central nervous system lymphoma (PCNSL) with combined high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. In an attempt to improve upon these dismal results, we treated seven PCNSL patients with HD-MTX-based induction therapy followed by thiotepa, busulfan, cyclophosphamide (TBC), and autologous stem cell transplant (ASCT), without WBRT. Six of these patients had at least one of the following poor prognostic features: Karnofsky performance status (KPS) p50%, age 460 years, or relapsed disease. All but one patient tolerated the treatment well and experienced improvements in neurological function and overall performance status posttransplant. No treatment-induced neurotoxicity (dementia, ataxia, and incontinence) was observed although the follow-up is short. One early treatment-related death occurred in a patient with multiple comorbid medical conditions. The other six patients achieved a complete response (CR) after TBC and ASCT. Five patients are currently alive and relapse-free at 5, 8, 24, 36, and 42 months from diagnosis. One additional patient relapsed and died 33 months after diagnosis. Two of the seven patients received TBC/ASCT as the only treatment after disease progression following their initial chemotherapy and both remain relapse-free at the time of this report, 22 and 31 months post-TBC/ASCT. In conclusion, prolonged CR can be attained after chemotherapy-only treatment of poor prognosis PCNSL. Furthermore, this small series suggests that high-dose chemotherapy for PCNSL should include drugs that penetrate the CNS such as busulfan and thiotepa rather than standard lymphoma regimens such as BEAM.

Autologous transplantation for relapsed non-Hodgkin's lymphoma using intravenous busulfan and cyclophosphamide as conditioning regimen: a single center experience

“…Due to excellent penetration of the blood-brain barrier, the combination of BU and CY-although not tested in this study-may be a better option for patients with central nervous system lymphoma. 22 It may also be a more desirable approach than CBV and BEAM for patients who have previously failed an etoposide containing salvage regimen. Overall, our results are comparable to those of other published regimens.…”

Primary central nervous system lymphoma: The role of consolidation treatment after a complete response to high‐dose methotrexate‐based chemotherapy

“…26 In addition, other clinical trials are using high-dose chemotherapy with stem cell rescue as a consolidation strategy with or without WBRT. [27][28][29][30][31][32] The role of consolidation therapy for PCNSL patients who achieved a CR after induction chemotherapy with MTX-based chemotherapy is still unclear. Long-term consequences of available consolidation strategies may outweigh the potential benefits, at least in elderly patients.…”

High-dose treosulfan in patients with relapsed or refractory high-grade lymphoma receiving tandem autologous blood stem cell transplantation

“…17 High-dose thiotepa is used in combination protocols with other alkylating drugs like busulfan and cyclophosphamide for patients with lymphoma or multiple myeloma. 18,19 The only way to assess the contribution of a single drug is to compare different combination regimens for efficacy and toxicity. This is a general problem in treatment situations in which combination protocols are used.…”