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. 2017 Dec;31(12):2807-2814.
doi: 10.1038/leu.2017.121. Epub 2017 Apr 25.

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

M Rasche  1 , C von Neuhoff  1 , M Dworzak  2 , J-P Bourquin  3 , J Bradtke  4 , G Göhring  5 , G Escherich  6 , G Fleischhack  1 , N Graf  7 , B Gruhn  8 , O A Haas  9 , T Klingebiel  10 , B Kremens  1 , T Lehrnbecher  10 , A von Stackelberg  11 , J Tchinda  3 , Z Zemanova  12 , C Thiede  13 , N von Neuhoff  1 , M Zimmermann  14 , U Creutzig  14 , D Reinhardt  1
Affiliations

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

M Rasche et al. Leukemia. 2017 Dec.

Abstract

We conducted a cytogenetic analysis of 642 children with de novo acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-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%, P<0.0001). An extremely poor outcome was observed for MK+/HK+ patients (n=10, EFS 10±10%, P<0.0001). 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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Schematic presentation of overlapping groups of patients with AML according to their cytogenetically defined karyotype. (b) Event-free survival of patients with complex (CK) and monosomal karyotype (MK). (c) EFS for patients with MK and hypodiploid karyotype (HK).
Figure 2
Figure 2
(a) Distribution of monosomies in patients with monosomal karyotype. n=number of monosomies; MK, monosomal karyotype. (b) EFS for patients with MK compared to patients with standard risk (SR), intermediate (MR) and other high-risk factors. (c) OS for patients with MK compared to patients with SR, intermediate risk and other high-risk factors. Definition of intermediate risk according to the AML-BFM 2012 protocol, defined as no favorable or high-risk criteria.
See this image and copyright information in PMC

References

    1. Harrison CJ, Hills RK, Moorman AV, Grimwade DJ, Hann I, Webb DK et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol 2010; 28: 2674–2681. - PubMed
    1. von Neuhoff C, Reinhardt D, Sander A, Zimmermann M, Bradtke J, Betts DR et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol 2010; 28: 2682–2689. - PubMed
    1. Campo E, Swerdlow S, Harris N, Pileri S, Stein H, Jaffe E. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon, France, 2008.
    1. Pession A, Masetti R, Rizzari C, Putti MC, Casale F, Fagioli F et al. Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia. Blood 2013; 122: 170–178. - PubMed
    1. Karol SE, Coustan-Smith E, Cao X, Shurtleff SA, Raimondi SC, Choi JK et al. Prognostic factors in children with acute myeloid leukaemia and excellent response to remission induction therapy. Br J Haematol 2015; 168: 94–101. - PMC - PubMed