International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Munster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)type primary therapy (80% +/- 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% +/- 7.2% and 50% +/- 12%, respectively). When ALL-or AML-specific gene fusions were excluded, 5-year EFS of CD19(+) leukemia was 83% +/- 5.3% on ALL-type primary treatment compared with 0% +/- 0% and 28% +/- 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19(+) ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19(-) and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with >= 5% blasts after remission induction. The results provide a basis for a prospective trial.