International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia
Hrusak, O; de Haas, V; Stancikova, J; Vakrmanova, B; Janotova, I; Mejstrikova, E; Capek, V; Trka, J; Zaliova, M; Luks, A; Bleckmann, K; Moricke, A; Irving, J; Konatkowska, B; Alexander, TB; Inaba, H; Schmiegelow, K; Stokley, S; Zemanova, Z; Moorman, AV; Rossi, JG; Felice, MS; Dalla-Pozza, L; Morales, J; Dworzak, M; Buldini, B; Basso, G; Campbell, M; Cabrera, ME; Marinov, N; Elitzur, S; Izraeli, S; Luria, D; Feuerstein, T; Kolenova, A; Svec, P; Kreminska, O; Rabin, KR; Polychronopoulou, S; da Costa, E; Marquart, HV; Kattamis, A; Ratei, R; Reinhardt, D; Choi, JK; Schrappe, M; Stary, J. Blood. 2018 Jul 19;132(3):264-276. doi: 10.1182/blood-2017-12-821363. Epub 2018 May 2. IF: 15.132
doc. MUDr. Ondřej Hrušák, Ph.D., Department of Paediatric Haematology and Oncology
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-Münster 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.