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Blood. 2018 Jul 19;132(3):264-276. doi: 10.1182/blood-2017-12-821363. Epub 2018 May 2.

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia.

Author information

Childhood Leukemia Investigation Prague, Prague, Czech Republic.
Department of Pediatric Hematology/Oncology, Charles University, Second Faculty of Medicine, Hospital Motol, Prague, Czech Republic.
Dutch Childhood Oncology Group, The Hague, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Bioinformatics Centre, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
University Medical Center, Christian Albrechts University Kiel, Kiel, Germany.
Department of Pediatrics, University Medical Center Schleswig Holstein, Campus Kiel, Kiel, Germany.
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
Department of Pediatric Hematology, Oncology and Transplantology, University of Medical Sciences, Poznan, Poland.
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.
Nordic Society for Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, The Juliane Marie Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Institute of Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark.
Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
Immunology and Rheumatology and.
Hematology and Oncology, Hospital Nacional de Pediatría Prof. Dr. J. P. Garrahan, Buenos Aires, Argentina.
Sydney Children's Hospital Network, Westmead, NSW, Australia.
Department of Pediatrics, Medical University of Vienna, St. Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria.
Laboratory of Pediatric Oncohematology, Department of Woman's and Child's Health, University of Padova, Padova, Italy.
National Program for Antineoplastic Drugs for Children (PINDA), Chilean National Pediatric Oncology Group, Hospital Roberto del Rio/Universidad de Chile, Santiago, Chile.
Hospital del Salvador, Universidad de Chile, Santiago, Chile.
Pediatric Hematology Oncology, Schneider Children's Medical Center, Petah-Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Comenius University Children's Hospital, Bratislava, Slovakia.
Center of Children's Oncohematology and BMT, National Children's Specialized Hospital "OHMATDYT," Kiev, Ukraine.
Pediatric Hematology/Oncology, Baylor College of Medicine, Houston, TX.
Department of Pediatric Hematology/Oncology, "Aghia Sophia" Children's Hospital, Athens, Greece.
Pediatrics Department, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
First Department of Pediatrics, University of Athens, Athens, Greece.
Helios Klinikum Berlin Buch, Berlin, Germany.
Pediatric Hematology and Oncology, University Children's Hospital Essen, Essen, Germany; and.
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.


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.

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