High-dose chemotherapy and autologous stem cell transplantation for secondary central nervous system lymphoma: many are called, but few are chosen.

R elapse of systemic lymphoma within the central nervous system (CNS) is a devastating event with very few long-term survivors after treatment with conventional therapy. High-dose chemotherapy employing CNS-penetrating agents with autologous stem cell support has demonstrated promise in prospective trials in primary CNS lymphoma, 1 and so has naturally gar-nered attention in secondary CNS lymphomas as well. Single-center retrospective studies have indeed suggested improved outcome favoring this approach, although such analyses have been limited by their retrospective nature, relatively few numbers of patients, and have provided little insight into how many patients with secondary CNS lymphoma are actually candidates for intensive therapy. 2-4 In this issue of Haematologica, Bromberg and colleagues , on behalf of the International Primary Central Nervous System Lymphomas Study Group, present a larger multicenter retrospective analysis of 92 patients with secondary CNS lymphoma treated in the modern era. 5 Their results confirm the poor overall prognosis in this population with a median overall survival of 7 months. Despite the fact that all patients were treated at stem cell transplant centers, only 29% of patients with CNS relapses underwent high-dose chemotherapy. The primary reasons for not undergoing high-dose chemotherapy were advanced age, comorbid disease, poor performance status, and lack of response to re-induction chemotherapy. Among patients who did undergo autologous stem cell transplantation, however, more than half of them remained alive 2 years later (54%), compared to only 17% of patients treated with less intensive therapy. This certainly suggests a clinical benefit favoring high-dose chemotherapy in these patients, but also reflects the more favorable risk characteristics of patients who are offered transplantation as they tend to be younger with better performance status, fewer comorbidities, and demonstrated chemosensitive disease. These issues notwithstanding, the findings do validate that a subset of patients with secondary CNS lymphoma may be treated more intensively and enjoy more favorable outcomes, perhaps even cures, than was previously considered possible in the setting of CNS recurrence of systemic lymphoma. These observations are further supported by data recently published in this Journal from the first prospective study of high-dose chemotherapy in secondary CNS lymphoma. 6 Patients under the age of 65 were enrolled and received sequential induction therapy with high-dose methotrexate, ifosfamide, dexamethasone and intrathe-cal liposomal cytarabine, followed by high-dose cytara-bine, thiotepa, dexamethasone, and liposomal cytara-bine. Responding patients then proceeded to high-dose chemotherapy with carmustine, thiotepa and etoposide with autologous stem cell support. Thirty patients …