Department of Paediatrics, Peking University People's Hospital, Peking University, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, China.
J Cancer Res Clin Oncol. 2021 Apr;147(4):1189-1201. doi: 10.1007/s00432-020-03406-4. Epub 2020 Oct 2.
Early death (ED) and treatment-related toxicity emerge as two major barriers for curing paediatric acute promyelocytic leukaemia (APL) patients. This study aims to investigate the effect of idarubicin on controlling hyperleukocytosis in induction therapy and the efficacy and safety of a risk-adapted attenuated consolidation chemotherapy.
We summarised the characteristics and long-term outcomes of 73 paediatric APL patients treated at our institution from February 2002 to October 2018, during which treatment protocols evolved over three periods and were defined as protocol A, B and C chronologically. All of the patients received an all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) combination remission induction therapy, with hydroxyurea (group A) or idarubicin (group B and C) to control hyperleukocytosis. Consolidation chemotherapy was modified with risk-adapted attenuated intensity and minimised cumulative doses of anthracyclines for group C (144 mg/m and 288 mg/m of daunorubicin equivalents for standard- and high-risk patients, respectively).
The median initial WBC, platelet count, and fibrinogen were 2.9 × 10/L (range 0.9-158.3 × 10/L), 32 × 10/L (range 4-226 × 10/L), and 160 mg/dL (range 53-549 mg/dL), respectively. High-risk and standard-risk were seen in 20.5% and 79.5% of patients, respectively. Three patients (4.1%) suffered early haemorrhagic death. At the end of induction therapy, 68 (93.2%) patients achieved haematologic complete remission (HCR). At a median follow-up of 91.97 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates for the whole cohort were 95.9 ± 2.3% and 88.7 ± 3.8%, respectively. A comparison of HCR rates and documented instances of toxicity between groups A and B + C showed no significant differences. However, idarubicin significantly reduced the peak WBC count (Z = - 3.292, P = 0.001) and duration of hyperleukocytosis (Z = - 2.827, P = 0.005). Estimated 3-year EFS (91.7 ± 8.0%) and OS (100%) rates for group C were not significantly different from those for group B, whereas the risk of treatment-related infections was significantly reduced (χ = 5.515, P = 0.019).
Idarubicin (8-10 mg/m/day for 2 days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated.
早期死亡（ED）和治疗相关的毒性是治愈儿科急性早幼粒细胞白血病（APL）患者的两大障碍。本研究旨在探讨柔红霉素在诱导治疗中控制白细胞增多症的效果，以及风险适应的减轻强度巩固化疗的疗效和安全性。
我们总结了 2002 年 2 月至 2018 年 10 月期间在我院治疗的 73 例儿科 APL 患者的特征和长期结果，在此期间，治疗方案在三个时期发生了演变，并按时间顺序定义为方案 A、B 和 C。所有患者均接受全反式维甲酸（ATRA）-三氧化二砷（ATO）联合缓解诱导治疗，用羟基脲（A 组）或柔红霉素（B 组和 C 组）控制白细胞增多症。C 组（标准和高危患者的柔红霉素当量分别为 144mg/m 和 288mg/m）的巩固化疗采用风险适应的减轻强度和最小化累积蒽环类药物剂量。
中位初始白细胞计数、血小板计数和纤维蛋白原分别为 2.9×10/L（范围 0.9-158.3×10/L）、32×10/L（范围 4-226×10/L）和 160mg/dL（范围 53-549mg/dL）。高危和标准危分别占 20.5%和 79.5%的患者。3 例（4.1%）患者早期出血死亡。诱导治疗结束时，68 例（93.2%）患者达到血液学完全缓解（HCR）。在中位随访 91.97 个月时，整个队列的 5 年总生存率（OS）和无事件生存率（EFS）估计分别为 95.9±2.3%和 88.7±3.8%。A 组和 B+C 组的 HCR 率和毒性记录实例比较，无显著差异。然而，柔红霉素显著降低了白细胞计数峰值（Z=-3.292，P=0.001）和白细胞增多症持续时间（Z=-2.827，P=0.005）。C 组的估计 3 年 EFS（91.7±8.0%）和 OS（100%）率与 B 组无显著差异，而治疗相关感染的风险显著降低（χ=5.515，P=0.019）。
柔红霉素（8-10mg/m/天，连用 2 天）用于诱导治疗中的白细胞增多症控制是安全有效的，适用于儿科 APL。建议采用风险适应的减轻强度巩固化疗。
