Relapsed or Refractory Burkitt Lymphoma in Children and Adolescents after BFM-Type First-Line Therapy - a BFM Group Report

Introduction: Current effective front-line therapies for Burkitt lymphoma leave few patients with relapsed or refractory disease. The objective of this analysis was to evaluate outcome, re-induction and SCT -approaches as well as risk factors in children and adolescents with progression or relapse of a Burkitt lymphoma/leukemia after current BFM-type first-line therapy.

Patients and Methods: We analyzed a population-based cohort of 145 children with relapsed Burkitt lymphoma/leukemia after BFM-type first-line therapy between 1986 and 2013. Recommended salvage until 2000 was BFM-type re-induction chemotherapy followed by autologous hematopoietic stem cell transplantation (SCT). From 2001 on different re-inductions were used, Rituximab was applied in relapse and both autologous and allogeneic SCT were performed.

Results:With a median follow-up of 8.2 (2.7-9.6) years, the 4-year survival after first relapse was 15±3%. Survival significantly improved for patients with relapse/progression after 2000 (until 2000, n=82: 11±3%, 2001 and later, n=63: 21±5%, p=.004) so that further risk factor analyses were performed on these 63 patients: Almost all patients with progression during front-line therapy (21/22), progression during re-induction (26/27), those not reaching CR before SCT (14/15) or not receiving rituximab during re-induction (9/9) died. Survival of 12 patients relapsing after initial therapy for low risk disease (R1/R2) was 42±14% compared to 16±5% for 51 patients relapsing after R3/R4-therapy (p=.02). CNS involvement could not be confirmed as statistically significant risk factor. Re-induction by CC (25 patients), ICE (8 patients), ICI (6 patients) or other regimen (11 patients) was followed by SCT in 31 patients (autologous, 18 patients; allogeneic, 13 patients). These approaches were associated with comparable survival of 16±5%. Two centers used a strategy of two to three courses of intensive continuous-infusion re-induction based on Vincristin (or Paclitaxel), Ifosfamide, Carboplatin, Idarubicine, Rituximab and intrathecal triple therapy without complete hematological regeneration between courses followed by allogeneic SCT. Survival of 8 patients treated this way was 63±17% (p=.034 as compared to the survival with other regimen). A center-effect may confound.

Conclusion: Patients with relapsed Burkitt lymphoma/leukemia still have a poor chance to survive after current effective front-line therapy. Time-condensed continuous-infusion re-induction with CD20-antibodies followed by SCT might form the basis for trials testing new drugs.