Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Department of Pediatrics, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.
Blood Adv. 2023 Nov 14;7(21):6532-6539. doi: 10.1182/bloodadvances.2022009381.
Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.
唐氏综合征（DS）患儿发生急性髓系白血病（AML）的风险显著增加，也称为与 DS 相关的髓系白血病（ML-DS）。与原发性 ML-DS 极高的预后形成鲜明对比的是，目前针对复发或难治性 ML-DS（r/r ML-DS）患儿的有限数据表明其预后较差。针对该人群，目前临床试验较少，也没有标准化的治疗方法。我们对国际研究小组和儿科肿瘤中心进行了回顾性分析，确定了 62 例 2000 年至 2021 年期间接受 r/r ML-DS 治疗的患者。从诊断到复发的中位时间为 6.8（范围，1.1-45.5）个月。3 年无事件生存率（EFS）和总生存率（OS）分别为 20.9±5.3%和 22.1±5.4%。生存与接受造血干细胞移植（HSCT）（风险比[HR]，0.28）、首次完全缓解（CR1）持续时间（HR，>12 个月为 0.31）和缓解后复发（HR，4.03）相关。在 HSCT 前达到完全缓解（CR）的患者的 OS 和 EFS 分别为 56.0±11.8%和 50.5±11.9%，优于未达到 CR 即进行 HSCT 的患者（3 年 OS 和 EFS 分别为 10.0±9.5%）。HSCT 后的治疗失败主要是由于疾病复发（52%），其次是治疗相关死亡率（10%）。即使在当前的治疗期间，r/r ML-DS 的预后仍然很差，可作为当前预后和未来干预性研究的参考点。需要开展旨在提高 r/r ML-DS 患者生存率的临床试验。
