Primary central nervous system lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. To date, there is no standardized treatment of PCNSL. Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation, such as autologous stem-cell transplantation (ASCT). In the present study, we have evaluated the toxicity and efficacy of high-dose consolidation with ASCT after chemotherapy induction in patients with newly diagnosed PCNSL.
In 2008, the Spanish group GELTAMO developed a clinical protocol for first-line treatment of patients with PCNSL, consisting of an induction chemotherapy with 2 cycles of BAM (BCNU 100 mg/m2 day 1, Ara-C 3000 mg/m2 days 9, 25 and 41, and methotrexate 2000 mg/m2 days 8, 24 y 40). Patients who achieved at least partial response (PR) received an intensification with high-dose chemotherapy (BCNU 400 mg/m2 day -6, and thiotepa 5 mg/Kg days -5 and -4) followed by ASCT (day 0), whereas BAM refractory patients received WBRT (45 Gy), salvage therapy or palliative treatment. To date, 70 patients have been included in the protocol. We present the preliminary analysis of 57 patients (median age 55 years, range 29-74) treated between July 2008 and November 2012.
BAM induction regimen was well tolerated, being the most common grade 3-4 toxicities: hematological (leucopenia in 32% of patients, thrombocytopenia in 15%), infectious (17%) and hepatic (5%). 33 out of 57 patients (58%) completed the 2 planned BAM cycles, achieving complete remission 19 patients (33,3%) and 8 (14%) PR. Reasons for not completing the 2 planned BAM courses were: lymphoma progression (n=21), and toxicity (n=3). 18 patients received WBRT, resulting in 5 and 9 patients achieving CR and PR, respectively. Regarding WBRT toxicity, 1 patient showed mild cognitive impairment, 3 leukoencephalopathy (2 mild, 1 severe), and 2 hydrocephalus. Finally, 24 patients (42%) underwent high-dose therapy and ASCT (18 after BAM and 6 after RT). Reasons for not performing the transplant were: progression of lymphoma (N=18), early death (N=2), comorbidities (N=3) or physician decision (N=10). After a median follow up of 22 months (4-49), 30 patients are alive (77% in CR), 26 patients have died (88% due to lymphoma progression, 8% due to infectious complications, and 4% due to other causes) and one patient have developed a secondary myelodysplastic syndrome (RAEB-2). Estimated 3-year progression-free survival and overall survival were 35% and 49%, respectively, for the whole series, and 65% and 85%, respectively, for transplanted patients.
This preliminary analysis shows that BAM induction regimen followed by high-dose therapy and ASCT shows an adequate toxicity profile and leads to prolonged remissions in approximately a third of patients with PCNSL. More than 50% of patients do not reach the transplant, mainly due to disease progression, but results after ASCT seem to be good. New induction regimens are needed in order to decrease the rate of early progression.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.