Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004

Abstract

We conducted a cytogenetic analysis of 642 children with de novo acute myeloid leukemia (AML) treated on the AML-BerlinFrankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK+ ), complex (CK+ ) and hypodiploid (HK+ ) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK+ (n = 22) as a new independent risk factor for poor event-free survival (EFS 23 ± 9% vs 53 ± 2% for all other patients, P = 0.0003), even after exclusion of four patients with monosomy 7 (EFS 28 ± 11%, P = 0.0081). CK+ patients without MK had a better prognosis (n = 47, EFS 47 ± 8%, P = 0.46) than those with MK+ (n = 12, EFS 25 ± 13%, P = 0.024). HK+ (n = 37, EFS 44 ± 8% for total cohort, P = 0.3) influenced outcome only when t(8;21) patients were excluded (remaining n = 16, EFS 9 ± 8%, Po0.0001). An extremely poor outcome was observed for MK+ /HK+ patients (n = 10, EFS 10 ± 10%, Po0.0001). Finally, isolated trisomy 8 was also associated with low EFS (n = 16, EFS 25 ± 11%, P = 0.0091). In conclusion, monosomal karyotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts.