High-dose chemotherapy with hematopoietic stem cell transplantation for the treatment of primary central nervous system lymphoma

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoid neoplasm for which current regimens utilizing standard-dose chemotherapy and/or radiation therapy lead to high relapse rates and/or unacceptable neurologic sequelae. High-dose chemotherapy followed by hematopoietic stem cell transplantation may overcome limitations of current treatment schemas. A search was performed of all English-language literature (1968 to June 2009) within the MEDLINE, EMBASE and Cochrane Library databases to identify relevant clinical trials using the terms stem cell transplantation, bone marrow transplantation, primary central nervous system lymphoma, and PCNSL. Bibliographies were reviewed to extract other relevant articles. Use of high-dose chemotherapy followed by hematopoietic stem cell transplantation for the treatment of PCNSL in a predominantly elderly population is feasible. Use of this treatment modality for newly diagnosed and recurrent or relapsed disease is burdened by a paucity of data guiding patient selection, optimal induction regimen, stem cell mobilization and conditioning chemotherapy. Data are also sparse and confounding regarding timing of initiation of this procedure relative to the natural history of the disease and timing of each chemotherapy regimen relative to each other. High-dose chemotherapy followed by hematopoietic stem cell transplantation remains an experimental procedure with insufficient data to guide clinicians. However, the data are encouraging and merit continued research to guide patient selection and treatment regimens which may produce optimal outcomes.

Putting caution in TEAM: high-dose chemotherapy with autologous HSCT for primary central nervous system lymphoma

“…Indeed, a recent review of clinical experience with PCNSL concluded that high-dose chemotherapy ± whole-brain radiotherapy followed by autologous HSCT holds promise to improve patient outcomes. 2 Although this latest review of PCNSL is thought-provoking, we find discrepancies that may confound the authors' conclusions.…”

“…2 Bearing in mind not only the variations in chemotherapy regimens, but also the variations of survival seen in these studies, we are surprised to find the authors' conclusion of superiority with 'thiotepa/busulfan based conditioning' and recommendation of this strategy as a 'suggested treatment approach in patients with PCNSL'. 1 Although these two agents may have a role in conditioning for autologous HSCT to treat newly-diagnosed PCNSL, the scarcity of data makes their role ill-defined.…”

“…6 Minimal improvements in survival were seen when using BEAM as a conditioning regimen for newly-diagnosed PCNSL following a high-dose MTX-based induction regimen, a finding attributed to lack of dose intensity in the central nervous system from etoposide, cytarabine and melphalan. 2,6 Clearly, TEAM is a variation of BEAM, with the primary differences being replacement of carmustine with thiotepa and modification to etoposide and/or cytarabine doses, depending on the comparator BEAM regimen. 7,8 Indeed, at the doses employed, carmustine penetrates the blood --brain barrier into the central nervous system most avidly in the four-drug BEAM regimen.…”

“…1 Although these two agents may have a role in conditioning for autologous HSCT to treat newly-diagnosed PCNSL, the scarcity of data makes their role ill-defined. 2 The majority of conditioning regimens employed in studies on newly-diagnosed PCNSL do not contain thiotepa and fewer still contain BU. 2 The total number of patients with newlydiagnosed PCNSL who had received a BU and thiotepa-based conditioning regimen before autologous HSCT was 53, a number far too small to use as the basis for an algorithm for the treatment of newly-diagnosed PCNSL patients.…”

“…2 The majority of conditioning regimens employed in studies on newly-diagnosed PCNSL do not contain thiotepa and fewer still contain BU. 2 The total number of patients with newlydiagnosed PCNSL who had received a BU and thiotepa-based conditioning regimen before autologous HSCT was 53, a number far too small to use as the basis for an algorithm for the treatment of newly-diagnosed PCNSL patients. 3,4,5 Additionally, we express our trepidation regarding the authors' preferred multi-agent conditioning regimen of thiotepa, etoposide, cytarabine, and melphalan (TEAM).…”