The Treatment of Burkitt Lymphoma with the Berlin-Frankfurt-Münster Protocol with Rituximab and Autologous Transplantation

Introduction: Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma; because of its fast growing rate, it often represents a clinical emergency. Intensive treatment approaches are required for adult BL, although a univocal standard of care still does not exist. The use of frontline autologous transplantation (ASCT) is debated. Methods: Between 2004 and 2020, 50 HIV-negative BL patients were treated with the Berlin-Frankfurt-Münster (BFM) protocol at our institution. Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, cytarabine), B (vincristine, cyclophosphamide, methotrexate, doxorubicin) and C (vindesine, methotrexate, etoposide, cytarabine), each repeated twice, every 28 days. Patients elder than 60 years did not receive block C, thus blocks A and B were repeated 3 times. Rituximab was given at day 1 each block. Central nervous system (CNS) prophylaxis with intrathecal cytarabine, methotrexate and dexamethasone was given once per each block. Autologous stem cells were harvested after the 4th or 5th cycles, with reinfusion (ASCT) at the end of the 6-blocks after BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning, when feasible. Results: Median age at onset was 38 years (range 16–72); 387 patients were male and 12 female. Stage III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Two patients did not receive rituximab because of adverse reaction and early death. Intrathecal prophylaxis was given in 96% of patients. Stem cell harvest was performed in 70% of patients, who all received a subsequent ASCT. The full 6-blocks treatment was completed in 70% of the patients; 8% received 5 cycles and 22% received ≤3 cycles. Early treatment interruption occurred because of disease progression (12%), toxicity (8%), death (4%) or other causes (4%). The overall response rate was 74%, with a complete response rate of 60%. Three patients could not be evaluated because of early progression/death. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, with both curves exhibiting a plateau. Likewise, 10-year disease-free survival was 80.3%. Eight patients had died because of disease progression (3 patients), infection or sepsis (4 patients) or cardiac arrest (1 patient). Grade 3–4 neutropenia, thrombocytopenia, anemia and mucositis were seen in 96%, 60%, 32% and 24% of patients, respectively. Infections occurred in 60% of patients, with grade 4 and fatal sepsis in 14% and 8% of cases, respectively. Methotrexate-related hepatic and renal toxicity occurred in 16% and 12% of patients, respectively, with complete recovery in all cases. Keywords: Chemotherapy, Immunotherapy, Stem Cell Transplant No conflicts of interests pertinent to the abstract.