TY - JOUR
T1 - Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients
T2 - Results of an international study
AU - Coenen, Eva A.
AU - Raimondi, Susana C.
AU - Harbott, Jochen
AU - Zimmermann, Martin
AU - Alonzo, Todd A.
AU - Auvrignon, Anne
AU - Beverloo, H. Berna
AU - Chang, Myron
AU - Creutzig, Ursula
AU - Dworzak, Michael N.
AU - Forestier, Erik
AU - Gibson, Brenda
AU - Hasle, Henrik
AU - Harrison, Christine J.
AU - Heerema, Nyla A.
AU - Kaspers, Gertjan J.L.
AU - Leszl, Anna
AU - Litvinko, Nathalia
AU - Lo Nigro, Luca
AU - Morimoto, Akira
AU - Perot, Christine
AU - Reinhardt, Dirk
AU - Rubnitz, Jeffrey E.
AU - Smith, Franklin O.
AU - Stary, Jan
AU - Stasevich, Irina
AU - Strehl, Sabine
AU - Taga, Takashi
AU - Tomizawa, Daisuke
AU - Webb, David
AU - Zemanova, Zuzana
AU - Pieters, Rob
AU - Zwaan, C. Michel
AU - Van Den Heuvel-Eibrink, Marry M.
PY - 2011/6/30
Y1 - 2011/6/30
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/79959822135
U2 - 10.1182/blood-2010-12-328302
DO - 10.1182/blood-2010-12-328302
M3 - Article
C2 - 21551233
AN - SCOPUS:79959822135
SN - 0006-4971
VL - 117
SP - 7102
EP - 7111
JO - Blood
JF - Blood
IS - 26
ER -