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 MorimotoChristine 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, Marry M. Van Den Heuvel-Eibrink

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358 Citations (Scopus)

Abstract

Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although 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 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 prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6; 11)(q27;q23) (HR = 2.2, P < .001); t(10; 11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .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.

Original languageEnglish
Pages (from-to)2489-2496
Number of pages8
JournalBlood
Volume114
Issue number12
DOIs
Publication statusPublished - 2009
Externally publishedYes

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