Matsuo H, Kajihara M, Tomizawa D, Watanabe T, Saito A M, Fujimoto J, Horibe K, Kodama K, Tokumasu M, Itoh H, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Tanaka S, Adachi S
Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
Department of Pediatrics, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Blood Cancer J. 2014 Jul 11;4(7):e226. doi: 10.1038/bcj.2014.47.
CCAAT/enhancer-binding protein alpha (CEBPA) mutations are a favorable prognostic factor in adult acute myeloid leukemia (AML) patients; however, few studies have examined their significance in pediatric AML patients. Here we examined the CEBPA mutation status and clinical outcomes of pediatric AML patients treated in the AML-05 study. We found that 47 (14.9%) of the 315 evaluable patients harbored mutations in CEBPA; 26 cases (8.3%) harbored a single mutation (CEBPA-single) and 21 (6.7%) harbored double or triple mutations (CEBPA-double). After excluding core-binding factor-AML cases, patients harboring CEBPA mutations showed better overall survival (OS; P=0.048), but not event-free survival (EFS; P=0.051), than wild-type patients. Multivariate analysis identified CEBPA-single and CEBPA-double as independent favorable prognostic factors for EFS in the total cohort (hazard ratio (HR): 0.47 and 0.33; P=0.02 and 0.01, respectively). CEBPA-double was also an independent favorable prognostic factor for OS (HR: 0.30; P=0.04). CEBPA-double remained an independent favorable factor for EFS (HR: 0.28; P=0.04) in the normal karyotype cohort. These results suggest that CEBPA mutations, particularly CEBPA-double, are an independent favorable prognostic factor in pediatric AML patients, which will have important implications for risk-stratified therapy.
CCAAT/增强子结合蛋白α（CEBPA）突变是成人急性髓系白血病（AML）患者的一个有利预后因素；然而，很少有研究探讨其在儿童AML患者中的意义。在此，我们研究了在AML-05研究中接受治疗的儿童AML患者的CEBPA突变状态和临床结局。我们发现，315例可评估患者中有47例（14.9%）存在CEBPA突变；26例（8.3%）为单突变（CEBPA-单突变），21例（6.7%）为双突变或三突变（CEBPA-双突变）。排除核心结合因子AML病例后，与野生型患者相比，携带CEBPA突变的患者总生存期（OS；P=0.048）较好，但无事件生存期（EFS；P=0.051）并非如此。多因素分析确定CEBPA-单突变和CEBPA-双突变是整个队列中EFS的独立有利预后因素（风险比（HR）：分别为0.47和0.33；P=0.02和0.01）。CEBPA-双突变也是OS的独立有利预后因素（HR：0.30；P=0.04）。在正常核型队列中，CEBPA-双突变仍然是EFS的独立有利因素（HR：0.28；P=0.04）。这些结果表明，CEBPA突变，尤其是CEBPA-双突变，是儿童AML患者的独立有利预后因素，这将对风险分层治疗具有重要意义。
