Autologous stem cell transplant in recurrent or refractory primary or secondary central nervous system lymphoma using thiotepa, busulfan and cyclophosphamide

Abstract

The prognosis for patients with central nervous system (CNS) involvement by recurrent or refractory diffuse large B-cell lymphoma is poor, with overall survival (OS) of 4-10 months. High-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) is a potential treatment alternative. We reviewed patients with recurrent primary (PCNSL) or secondary (SCNSL) CNS lymphoma referred for consolidation HDC-ASCT utilizing thiotepa, busulfan and cyclophosphamide (TBC). Among the 17 patients included, all had achieved a complete remission after salvage induction chemotherapy, which incorporated methotrexate in 82% of patients. Two patients failed stem-cell harvesting and 15 (88%) underwent transplant. The estimated 3-year progression-free survival (PFS) and OS were both 93% (95% confidence interval 61-99%). Median PFS and OS were not reached. There was no transplant-related mortality. These results confirm the benefit of TBC followed by ASCT in select patients with recurrent PCNSL and suggest a potential role for the regimen in those with SCNSL. Further investigation is warranted.

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

“…Among transplanted patients (N 5 27), PFS was 41 months. Three patients died of CYVE, but there were no transplant-related deaths, which is in line with other studies on TBC in CNS lymphomas 24,25 and other malignancies, 26-28 all reporting transplantrelated mortality under 5%. In our study, treatment-related mortality appeared higher, but it is difficult to determine if this could be because of a higher susceptibility specific to PCNSL patients, or if it could reflect a less selected patient population, as compared with recurrent disease patients receiving TBC after surviving highly toxic salvage chemotherapies, such as CYVE.…”

“…16,[22][23][24][25] In a multicenter phase-2 study (N 5 43), 16 TBC was used following a cytarabine/etoposide (CYVE) salvage chemotherapy, achieving PFS of 12 months and OS of 18 months. Among transplanted patients (N 5 27), PFS was 41 months.…”

“…Therefore, it is difficult to assess whether such patients with a more favorable prognosis 40 could have achieved similar results with R-MPV alone and without any consolidation treatment. It is noteworthy that salvage treatments including TBC-based HDC-ASCT 16,24 or even WBRT 41,42 are also effective in this population and will require further investigation. Ongoing study Radiation Therapy Oncology Group 1114 is investigating R-MPV with and without reduced-dose WBRT and will provide further data on the relevance of consolidation treatments in newly diagnosed PCNSL.…”

Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review

“…The corresponding TRM values were 16 and 21% for patients who had already undergone radiotherapy (N = 59 50 ). Omuro et al 93 Welch et al 94 Cote et al 95 Gopal et al 100% across the studies. Kidney failure was reported in three patients across studies.…”

The role of autologous stem cell transplantation in primary central nervous system lymphoma

“…Preliminary studies on TBC combination were performed on small and heterogeneous retrospective series, sometimes combining patients with PCNSL and secondary CNS lymphoma, as well as with untreated and relapsed disease, with consequent difficulties to interpret results. 27,28,36,43 In the largest retrospective series, the 5-year OS of patients treated with HD-MTXbased induction followed by TBC-conditioned ASCT was 44%. 27 Post-ASCT relapses displayed notable aggressiveness and chemorefractoriness.…”