Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Pediatric Hematology and Oncology, Pediatrics III, Essen University Hospital, Essen, Germany.
Blood. 2017 Jun 22;129(25):3314-3321. doi: 10.1182/blood-2017-01-765057. Epub 2017 Apr 11.
Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% ± 3% vs 90% ± 4%; = .64), event-free survival (EFS; 87% ± 3% vs 89% ± 4%; = .71), and cumulative incidence of relapse/nonresponse (CIR/NR; 6% ± 3% vs 6% ± 2%; = .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% ± 16% vs 88% ± 3%; = .0008) and gain of chromosome 8 (CIR/NR, 16% ± 7% vs 3% ± 2%, = .02; 5-year EFS, 73% ± 8% vs 91% ± 4%, = .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2.
患有唐氏综合征相关髓性白血病（ML-DS）的儿童与非 DS 患者相比，预后较好，但对细胞毒性药物的敏感性更高。我们分析了北欧儿科血液学和肿瘤学学会（NOPHO）、荷兰儿童肿瘤学组（DCOG）和急性髓性白血病-柏林-法兰克福-明斯特（AML-BFM）研究组开展的前瞻性、多中心、开放性、非随机 ML-DS 2006 试验中 170 例儿科 ML-DS 患者的结果。与 AML-BFM 98 试验中用于 ML-DS 患者的低强度方案的历史对照组相比，通过降低依托泊苷累积剂量（950 至 450mg/m）和减少鞘内中枢神经系统预防，同时省略维持治疗，降低了治疗强度。尽管如此，5 年总生存率（89%±3%比 90%±4%；=0.64）、无事件生存率（EFS；87%±3%比 89%±4%；=0.71）和复发/无反应累积发生率（CIR/NR；6%±3%比 6%±2%；=0.03）在 ML-DS 2006 试验和历史对照组之间没有显著差异。早期治疗反应差（5 年 EFS，58%±16%比 88%±3%；=0.0008）和获得 8 号染色体（CIR/NR，16%±7%比 3%±2%，=0.02；5 年 EFS，73%±8%比 91%±4%，=0.018）被确定为预测 EFS 较差的独立预后因素。7 例有细胞遗传学数据的复发患者中有 5 例（71%）存在三体 8。本研究揭示了 ML-DS 儿童的预后标志物，并表明降低治疗并未损害优异的结果。该试验在 EudraCT 上注册为 #2007-006219-2。
