高危儿童急性早幼粒细胞白血病临床分析

Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia

目的:探讨高危初治儿童急性早幼粒细胞白血病的诊疗过程,为改善预后提供经验。方法:回顾性分析2015年1月-2021年6月本院收治的24例高危初治急性早幼粒细胞白血病患儿的临床资料。结果:24例患儿以皮肤、牙龈或鼻出血为主要表现,其中男性15例,女性9例,中位年龄7岁,中位白细胞数为28.98(10-232)×10^(9)/L,其中白细胞数介于(10-50)×10^(9)/L者15例,介于(50-100)×10^(9)/L者2例,>100×10^(9)/L者7例。2015年-2016年11月收治的3例患儿中2例白细胞数>100×10^(9)/L,其中1例先使用高三尖杉酯碱减瘤,7 d后基因确诊加用全反式维甲酸(ATRA)d3出现分化综合征及肺出血死亡;另1例给予减量ATRA+柔红霉素+亚砷酸诱导治疗达完全缓解;第3例白细胞数为12×10^(9)/L,入院前存在脑出血,治疗d7死亡。其余21例按华南儿童APL方案化疗,其中5例白细胞数>100×10^(9)/L,2例介于(50-100)×10^(9)/L,14例介于(10-50)×10^(9)/L。5例白细胞数>100×10^(9)/L患儿中,1例于口服ATRA d2还未加蒽环类药即出现脑出血昏迷死亡,3例口服ATRA d2加用蒽环类药物化疗后出现脑出血死亡,另1例口服ATRA d2加用米托蒽醌化疗后出现分化综合征,给予ATRA减量达完全缓解,目前无病存活。2例白细胞数介于(50-100)×10^(9)/L的患儿中,1例于口服ATRA d2还未加蒽环类药即出现脑出血昏迷死亡。所有患儿随访至2021年8月1日,中位随访时间为40个月,其中死亡7例,1例维持治疗中复发,再次化疗后达二次缓解,3年整体生存14例,3年无事件生存13例。死亡的7例患儿,从治疗到死亡中位时间为5 d,其中1例白细胞数介于(10-50)×10^(9)/L,1例介于(50-100)×10^(9)/L,其余5例均>100×10^(9)/L。结论:白细胞数>100×10^(9)/L的高危急性早幼粒细胞白血病患儿死亡率高,小剂量开始逐渐加量化疗及尽早加亚砷酸可能有助于改善预后。

Objective: To explore the treatment of children with high-risk acute promyelocytic leukemia(APL), aiming to improve the prognosis. Methods: The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed. Results: The main manifestations of 24 children(including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98(10-232)×10^(9)/L, including 15 cases with leukocyte count between 10×10^(9)/L and 50×10^(9)/L, 2 cases between 50×10^(9)/L and 100×10^(9)/L, and 7 cases >100×10^(9)/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×10^(9)/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid(ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide(ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×10^(9)/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×10^(9)/L and 50×10^(9)/L, 2 cases between 50×10^(9)/L and 100×10^(9)/L, and 5 cases >100×10^(9)/L. In the 5 children with leukocyte count >100×10^(9)/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×10^(9)/L and 100×10^(9)/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×10^(9)/L and 50×10^(9)/L, 1 case between 50×10^(9)/L and 100×10^(9)/L, and 5 cases >100×10^(9)/L. Conclusion: High-risk APL children with leukocyte count >100×10^(9)/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.