Rasche M, von Neuhoff C, Dworzak M, Bourquin J-P, Bradtke J, Göhring G, Escherich G, Fleischhack G, Graf N, Gruhn B, Haas O A, Klingebiel T, Kremens B, Lehrnbecher T, von Stackelberg A, Tchinda J, Zemanova Z, Thiede C, von Neuhoff N, Zimmermann M, Creutzig U, Reinhardt D
Department of Pediatric Hematology/Oncology, Pediatrics III, University Hospital of Essen, Essen, Germany.
Department of Pediatrics, St Anna Children's Hospital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
Leukemia. 2017 Dec;31(12):2807-2814. doi: 10.1038/leu.2017.121. Epub 2017 Apr 25.
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.
我们对642例接受AML-柏林-法兰克福-明斯特（BFM）04方案治疗的初发性急性髓系白血病（AML）儿童进行了细胞遗传学分析，以确定特定染色体畸变的预后价值，这些畸变包括单体核型（MK）、复杂核型（CK）和亚二倍体核型（HK），单独及联合分析。多变量回归分析特别确定MK（n=22）是无事件生存期（EFS）差的一个新的独立危险因素（所有其他患者的EFS为53±2%，而MK患者为23±9%，P=0.0003），即使排除4例7号染色体单体患者后也是如此（EFS为28±11%，P=0.0081）。无MK的CK患者（n=47，EFS为47±8%，P=0.46）比有MK的患者（n=12，EFS为25±13%，P=0.024）预后更好。HK（n=37，全队列EFS为44±8%，P=0.3）仅在排除t(8;21)患者时（剩余n=16，EFS为9±8%，P<0.0001）影响预后。MK/HK患者预后极差（n=10，EFS为10±10%，P<0.0001）。最后，孤立的8号染色体三体也与低EFS相关（n=16，EFS为25±11%，P=0.0091）。总之，单体核型是高危儿童AML的一个强有力的独立预测因素。此外，孤立的8号染色体三体和无t(8;21)的亚二倍体与不良预后一致。这些结果对风险分层具有重要意义，应在独立的儿童队列中进一步验证。
