Abstract

Data on childhood acute promyelocytic leukemia (APL) from low-and middle-income countries is limited. Early mortality is a concern and often not highlighted in clinical trials. The retrospective study was conducted on patients (≤12 years) with APL from 2003 to 2021 at a single center in India. Patients were treated with all-trans-retinoic acid (ATRA) and chemotherapy. Induction and three courses of consolidation were followed by maintenance for 2 years. In 2015, the protocol was updated with following modifications: (a) obtaining diagnostic cerebrospinal fluid at end-of-induction rather than at diagnosis, (b) administering intrathecal cytarabine regardless of risk-category, (c) risk-stratified administration of chemotherapy, and (d) inclusion of ATRA in all the cycles of consolidation. Sixty-two patients were diagnosed over the 17 years. The median age was 8 years (range: 0.9–12). Half had high-risk disease. Differentiation syndrome was observed in 32%, none being fatal. Eighteen (29%) patients died due to hemorrhage (83%) or septicemia (17%). Thirteen (21%) had early mortality (≤15 days), all due to hemorrhage. A platelet count <20 × 10⁹/L predicted early mortality (odds ratio: 4.5; 95% CI: 0.9–22, p = 0.06). Treatment abandonment reduced from 23.5% during 2003–2015 to nil during 2015–2021 (p = 0.006). Three (8%) patients relapsed. The 4-year OS of all patients and the patients who survived >15 days was 70.1% and 89.6%, respectively. The 4-year EFS, including abandonment and early mortality, before and following updated protocol, was 61.4% and 65.5%, respectively (p = 0.77). Early mortality continues to be a barrier to an otherwise excellent survival in childhood APL. A significant reduction in treatment abandonment in recent years is gratifying.

摘要

来自低收入和中等收入国家的儿童急性早幼粒细胞白血病 (APL) 数据有限。早期死亡率是一个问题，在临床试验中通常不会强调。该回顾性研究是在印度的一个中心对 2003 年至 2021 年 APL 患者（≤12 岁）进行的。患者接受全反式治疗视黄酸 (ATRA) 和化疗。诱导和三个疗程的巩固之后是维持 2 年。2015 年，该方案经过以下修改进行了更新：(a) 在诱导结束时而不是在诊断时获取诊断性脑脊液，(b) 无论风险类别如何，都进行鞘内注射阿糖胞苷，(c) 进行风险分层化疗和 (d) 将 ATRA 纳入所有整合周期。在 17 年的时间里，有 62 名患者被确诊。中位年龄为 8 岁（范围：0.9–12）。一半患有高危疾病。在 32% 的患者中观察到分化综合征，没有一例是致命的。18 名 (29%) 患者死于出血 (83%) 或败血症 (17%)。13 例 (21%) 早期死亡（≤15 天），均因出血所致。血小板计数 <20 × 10 ⁹/L 预测早期死亡率（比值比：4.5；95% CI：0.9–22，p  = 0.06）。放弃治疗的比例从 2003-2015 年的 23.5% 降至 2015-2021 年的零 ( p  = 0.006)。三名 (8%) 患者复发。所有患者和存活>15 天的患者的 4 年 OS 分别为 70.1% 和 89.6%。更新方案前后的 4 年 EFS，包括放弃率和早期死亡率，分别为 61.4% 和 65.5% ( p  = 0.77)。过早死亡仍然是儿童 APL 其他方面出色生存的障碍。近年来放弃治疗的显着减少令人欣慰。