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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.

SUBMITTER: Coenen EA 

PROVIDER: S-EPMC3143552 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study.

Coenen Eva A EA   Raimondi Susana C SC   Harbott Jochen J   Zimmermann Martin M   Alonzo Todd A TA   Auvrignon Anne A   Beverloo H Berna HB   Chang Myron M   Creutzig Ursula U   Dworzak Michael N MN   Forestier Erik E   Gibson Brenda B   Hasle Henrik H   Harrison Christine J CJ   Heerema Nyla A NA   Kaspers Gertjan J L GJ   Leszl Anna A   Litvinko Nathalia N   Lo Nigro Luca L   Morimoto Akira A   Perot Christine C   Reinhardt Dirk D   Rubnitz Jeffrey E JE   Smith Franklin O FO   Stary Jan J   Stasevich Irina I   Strehl Sabine S   Taga Takashi T   Tomizawa Daisuke D   Webb David D   Zemanova Zuzana Z   Pieters Rob R   Zwaan C Michel CM   van den Heuvel-Eibrink Marry M MM  

Blood 20110506 26


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%), in  ...[more]

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