International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

Ondrej Hrusak, Valerie De Haas, Jitka Stancikova, Barbora Vakrmanova, Iveta Janotova, Ester Mejstrikova, Vaclav Capek, Jan Trka, Marketa Zaliova, Ales Luks, Kirsten Bleckmann, Anja Möricke, Julie Irving, Benigna Konatkowska, Thomas B. Alexander, Hiroto Inaba, Kjeld Schmiegelow, Simone Stokley, Zuzana Zemanova, Anthony V. MoormanJorge Gabriel Rossi, Maria Sara Felice, Luciano Dalla-Pozza, Jessa Morales, Michael Dworzak, Barbara Buldini, Giuseppe Basso, Myriam Campbell, Maria Elena Cabrera, Neda Marinov, Sarah Elitzur, Shai Izraeli, Drorit Luria, Tamar Feuerstein, Alexandra Kolenova, Peter Svec, Olena Kreminska, Karen R. Rabin, Sophia Polychronopoulou, Elaine Da Costa, Hanne Vibeke Marquart, Antonis Kattamis, Richard Ratei, Dirk Reinhardt, John K. Choi, Martin Schrappe, Jan Stary

Research output: Contribution to journalArticle

Abstract

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% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD191 leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 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 CD191 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 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. (Blood. 2018;132(3):264-276)

Original languageEnglish (US)
Pages (from-to)264-276
Number of pages13
JournalBlood
Volume132
Issue number3
DOIs
StatePublished - Jul 19 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia'. Together they form a unique fingerprint.

  • Cite this

    Hrusak, O., De Haas, V., Stancikova, J., Vakrmanova, B., Janotova, I., Mejstrikova, E., Capek, V., Trka, J., Zaliova, M., Luks, A., Bleckmann, K., Möricke, A., Irving, J., Konatkowska, B., Alexander, T. B., Inaba, H., Schmiegelow, K., Stokley, S., Zemanova, Z., ... Stary, J. (2018). International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood, 132(3), 264-276. https://doi.org/10.1182/blood-2017-12-821363