Progressive or Relapsed Burkitt Lymphoma or Leukemia in Children and Adolescents after BFM-type First-line Therapy

Children with refractory or relapsed Burkitt lymphoma have a poor chance to survive. We describe characteristics, outcome, re-induction and transplantation-approaches and evaluate risk factors among children with progression of a Burkitt lymphoma/leukemia included in NHL-BFM studies between 1986 and 2016. Treatment recommendation was re-induction including rituximab from the early 2000s followed by blood stem cell transplantation. The 3-year survival of the 157 children was 18.5{plus minus}3%. Survival significantly improved from 11{plus minus}3% before to 27{plus minus}5% after 2000 (p<.001) allowing for risk factor analyses among the latter 75 patients, of whom 28 had disease progressive during initial therapy. Survival of 14 patients with relapse after initial therapy for low risk disease (R1/R2) was 50{plus minus}13% compared to 21{plus minus}5% for 61 patients progressing after R3/R4-therapy (p<.02). 25 of 28 patients with progression during first-line therapy, 31 of 32 with progression during re-induction, 15 of 16 not reaching a complete remission before transplantation, 9 of 10 treated with rituximab front-line and all 13 patients not receiving rituximab during re-induction died. 46 patients received stem cell transplantation (20 autologous, 26 allogeneic). Survival after a regimen combining Rituximab with continuous-infusion chemotherapy followed by allogeneic transplantation was 67{plus minus}12% compared to 18{plus minus}5% for all other regimen and transplantations (p=.003). Patients with relapsed Burkitt lymphoma/leukemia have a poor chance to survive after current effective front-line therapies. Progression during initial or re-induction chemotherapy and initial high-risk disease are risk-factors in relapse. Time-condensed continuous-infusion re-induction followed by stem cell transplantation forms the basis for testing new drugs.