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International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

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  • 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 Moorman
  • Jorge 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
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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.

Original languageEnglish
JournalBlood
Volume132
Issue number3
Pages (from-to)264-276
Number of pages13
ISSN0006-4971
DOIs
Publication statusPublished - 19 Jul 2018

ID: 55401316