title: Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.
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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Balgobind
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Anne
authors.initials: A
authors.lastname: Auvrignon
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dworzak
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.forename: Brenda
authors.initials: B
authors.lastname: Gibson
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Anna
authors.initials: A
authors.lastname: Leszl
authors.forename: Nathalia
authors.initials: N
authors.lastname: Litvinko
authors.forename: Luca Lo
authors.initials: LL
authors.lastname: Nigro
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Christine
authors.initials: C
authors.lastname: Perot
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Irina
authors.initials: I
authors.lastname: Stasevich
authors.forename: Sabine
authors.initials: S
authors.lastname: Strehl
authors.forename: Takashi
authors.initials: T
authors.lastname: Taga
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.forename: David
authors.initials: D
authors.lastname: Webb
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanova
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D018572:Disease-Free Survival; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007390:International Agencies; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase