Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: A retrospective study by the I-BFM study group

Sanne Noort, Martin Zimmermann, Dirk Reinhardt, Wendy Cuccuini, Martina Pigazzi, Jenny Smith, Rhonda E. Ries, Todd A. Alonzo, Betsy Hirsch, Daisuke Tomizawa, Franco Locatelli, Tanja A. Gruber, Susana Raimondi, Edwin Sonneveld, Daniel K. Cheuk, Michael Dworzak, Jan Stary, Jonas Abrahamsson, Nira Arad-Cohen, Malgorzata CzogalaBarbara De Moerloose, Henrik Hasle, Soheil Meshinchi, Marry Van Den Heuvel-Eibrink, C. Michel Zwaan

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43 Scopus citations


To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n 5 23) had significantly lower median white blood cell count (12.5 3 109/L, P 5 .03) compared with the reference cohort. FUS-ERG rearranged AML (n 5 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P 5 .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] 5 5%), significantly lower compared with the reference cohort (51%, SE 5 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE 5 8%, P 5 .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE 5 8%) in FUS-ERG, 0% (SE 5 0%) in RUNX1-CBFA2T3, compared with 32% (SE 5 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P 5 .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.

Original languageEnglish (US)
Pages (from-to)1548-1592
Number of pages45
Issue number15
StatePublished - Oct 11 2018

Bibliographical note

Funding Information:
1Pediatric Oncology/Hematology, Erasmus MC–Sophia Children’s Hospital Rotterdam, Rotterdam, The Netherlands; 2Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany; 3Acute Myeloid Leukemia-Berlin-Frankfurt-Münster Study Group, Pediatric Hematology and Oncology, Essen, Germany; 4Department of Cytogenetics, Saint Louis Hospital, Paris, France; 5Women and Children’s Health, Hematology-Oncology Laboratory, University of Padova, Padova, Italy; 6Fred Hutchinson Cancer Research Center, Seattle, WA; 7Children’s Oncology Group, Monrovia, CA; 8Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan; 9Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome, Italy; 10Department of Pediatric Sciences, University of Pavia, Pavia, Italy; 11Department of Oncology and 12Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN; 13Dutch Childhood Oncology Group, The Hague, The Netherlands; 14Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong; 15Department of Pediatrics, Children’s Cancer Research Institute and St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria; 16Czech Pediatric Hematology/Oncology, University Hospital Motol and Charles University, Prague, Czech Republic; 17Nordic Society for Pediatric Hematology and Oncology, Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 18Pediatric Hemato-Oncology Department, Ruth Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa, Israel; 19Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland; 20Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium; 21Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; 22Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA; and 23Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

Publisher Copyright:
© 2018 by The American Society of Hematology.


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