High-dose chemotherapy supported by autologous stem cell transplantation in patients with primary central nervous system lymphoma: facts and opinions

Abstract

The standard approach to primary central nervous system lymphomas (PCNSL), that is high-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain irradiation (WBRT), is associated with disappointing outcome. Moreover, this strategy is heavily conditioned by increased risk of disabling neurotoxicity, mostly among elderly patients. Several drugs and strategies have been investigated to improve results and neurotolerability. Among others, some investigators focused on the use of high-dose chemotherapy supported by autologous stem cells transplant (HDC/ASCT) as consolidation after primary chemotherapy. This approach has been used as salvage therapy in patients who experienced progressive disease or relapse after conventional chemo-radiotherapy or as consolidation after primary HD-MTX-based chemotherapy, replacing or preceding WBRT. Evidence supporting the role of HDC/ASCT is growing but several questions are still unanswered. The best conditioning regimen, the role of concomitant intrathecal chemotherapy, the neurotoxicity risk of further WBRT after transplant, the best time for response assessment and late effects both on neurological performance and extraneural organs remain to be characterised. This critical review is focused on the analysis of published experiences on HDC/ASCT in PCNSL in order to provide preliminary answers to the most pressing questions in this field.

Feasibility of BU, CY and etoposide (BUCYE), and auto-SCT in patients with newly diagnosed primary CNS lymphoma: a single-center experience

“…9,11,23,24 However, this treatment is known to be associated with increased toxicity in elderly patients. Two of the three patients aged more than 60 years in a series involving a total of seven patients experienced significant complications.…”

Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases

“…A meta-analysis of IC+HCR in PCNSL showed a trend toward better therapeutic results when the IC was based on thiotepa plus carmustine or busulfan. 9 Our results would need to be compared with a series of PCNSL patients who received the BEAM regimen to define the role of the association of thiotepa, busulfan and cyclophosphamide in PCNSL. Our series included patients who relapsed after first-line treatment as well as primary refractory patients; this differs from other published series that report the results of salvage treatment in non-Hodgkin's lymphomas.…”

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

“…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.…”

“…The only agent in this regimen that has appreciable blood --brain barrier penetration at the doses referenced is thiotepa, even in patients with impaired blood --brain barrier due to PCNSL. 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. 6 However, the replacement of carmustine with thiotepa resulted from concerns over pulmonary toxicity and not out of any benefit in blood brain barrier penetration with thiotepa. 9 It stands to reason that similar outcomes would be expected with the use of TEAM compared with those, which have historically been seen with BEAM.…”