title: Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study.
abstract: We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P < .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Coenen
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
authors.initials: L
authors.lastname: Lo Nigro
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Christine
authors.initials: C
authors.lastname: Perot
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: Rob
authors.initials: R
authors.lastname: Pieters
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; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D015321:Gene Rearrangement; D056726:Genetic Association Studies; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014178:Translocation, Genetic; D014314:Trisomy
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase