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Blood, 17 September 2009, Vol. 114, No. 12, pp. 2489-2496.
Prepublished online as a Blood First Edition Paper on June 15, 2009; DOI 10.1182/blood-2009-04-215152.
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Submitted April 6, 2009
Accepted May 21, 2009
Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study
Brian V. Balgobind, Susana C. Raimondi, Jochen Harbott, Martin Zimmermann, Todd A. Alonzo, Anne Auvrignon, H. Berna Beverloo, Myron Chang, Ursula Creutzig, Michael N. Dworzak, Erik Forestier, Brenda Gibson, Henrik Hasle, Christine J. Harrison, Nyla A. Heerema, Gertjan J.L. Kaspers, Anna Leszl, Nathalia Litvinko, Luca Lo Nigro, Akira Morimoto, Christine Perot, Rob Pieters, Dirk Reinhardt, Jeffrey E. Rubnitz, Franklin O. Smith, Jan Stary, Irina Stasevich, Sabine Strehl, Takashi Taga, Daisuke Tomizawa, David Webb, Zuzana Zemanova, C. Michel Zwaan, and Marry M. van den Heuvel-Eibrink*
Department of Pediatric Oncology/Hematology, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands
St. Jude Children's Research Hospital, Memphis, TN, United States
AML-BFM Study Group, Department of Pediatric Hematology and Oncology, University of Giessen, Giessen, Germany
AML-BFM Study Group, Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany
Children's Oncology Group (COG), Arcadia, CA, United States
French Leucemie Aique Myeloide Enfant (LAME), Hopital Trousseau, Paris, France
Dutch Childhood Oncology Group (DCOG), Dutch Working group on Hemato-Oncologic Genome Diagnostics, The Hague, Netherlands
Children's Oncology Group (COG), Data Centre, Gainesville, FL, United States
AML-BFM Study Group, Pediatric Hematology/Oncology, University Hospital, Munster, Germany
Children's Cancer Research Institute, Vienna, Austria
Nordic Society for Pediatric Hematology and Oncology (NOPHO),Department of Clinical Science, Pediatrics, Umea University Hospital, Umea, Sweden
Department of Pediatric Oncology/Hematology, Royal Hospital for Sick Children, Glasgow, United Kingdom
Nordic Society for Pediatric Hematology and Oncology (NOPHO),Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom
Department of Pathology, The Ohio State University, Columbus, OH, United States
Dutch Childhood Oncology Group (DCOG), The Hague, Netherlands
Italian Association of Pediatric Hematology Oncology (AIEOP), Clinica Pediatrica, Universita Padova, Padova, Italy
Research Center for Pediatric Oncology and Hematology, Minsk, Belarus
Italian Association of Pediatric Hematology Oncology (AIEOP), Clinica Pediatrica, Universita Catania, Catania, Italy
Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG), Japan
Hematology/Oncology and Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, United States
Czech Pediatric Hematology/Oncology (CPH), University Hospital Motol and 2nd Medical School, Charles University, Prague, Czech Republic
Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan
Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
Great Ormond Street Hospital for Children, London, United Kingdom
Center of Oncocytogenetics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
* Corresponding author; email: m.vandenheuvel{at}erasmusmc.nl.
Translocations involving chromosome 11q23 frequently occur in pediatric AML and are associated with poor prognosis. In most cases, the MLL-gene localized at 11q23 is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce, because most collaborative group 11q23 series are too small for meaningful analysis of subgroups, though some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups (15 countries) to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44%±5%, with large differences across subgroups (11%±5% to 92%±5%). Multivariate analysis identified the following subgroups as independent predictors of prognosis: t(1;11)(q21;q23), (HR 0.1,p=0.004); t(6;11)(q27;q23), (HR 2.2,p<0.001); t(10;11)(p12;q23), (HR 1.5,p=0.005); and t(10;11)(p11.2;q23), (HR 2.5,p=0.005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.
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