目的

探讨首发及复发时均伴颅内出血（ICH），并且融合基因为核磷蛋白-维甲酸受体α（NPM-RARα）的变异型急性早幼粒细胞白血病（v APL）患儿临床特点。

方法

选择2020年12月成都市妇女儿童中心医院收治的1例v APL 女性患儿（患儿1）为研究对象。回顾性分析其临床表现、实验室及影像学检查结果，以及治疗过程和转归。检索国内、外数据库中NPM-RARα 融合基因呈阳性的v APL患儿相关研究文献进行文献复习。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》。监护人对患儿诊治过程均知情同意，并签署临床研究知情同意书。

结果

①患儿1，女性，首次发病年龄为3岁9个月，因“剧烈头痛、呕吐、血常规异常”入院。入院后血常规提示三系异常，凝血功能异常。骨髓形态学及免疫分型提示为髓系白血病、融合基因检测结果为NPM-RARα 呈阳性，故其被临床诊断为v APL。因其初诊时白细胞计数（WBC）＞100×10⁹/L，故采取高危急性早幼粒细胞白血病（APL）化疗方案。患儿1病初头颅CT 见ICH，经过全反式维甲酸（ATRA）+三氧化二砷（ATO）为基础的诱导缓解化疗，ICH 病灶吸收，融合基因转阴。在维持治疗第2个周期时，患儿1融合基因复阳，连续给予伊达比星（IDA）联合阿糖胞苷（Ara-C）化疗2个疗程后，骨髓形态学及融合基因再次转阴；2021年9月（4岁6个月龄）时，患儿1骨髓形态学复发，再次发生ICH 并发脑疝，最终因呼吸循环衰竭死亡，总体生存时间为9个月。②文献复习：检索到关于NPM-RARα 融合基因阳性的儿童v APL研究文献共计5篇，涉及5例v APL患儿（患儿2～6），对包括患儿1在内6例v APL患儿病例资料进行分析的结果显示，3例（患儿1、3、4）复发，1例（患儿5）持续完全缓解（CR），1 例（患儿4）复发后再次CR，1 例（患儿6）缺少随访结果；患儿1、2 死亡。

结论

NPM-RARα 融合基因呈阳性的儿童v APL 临床罕见，目前临床采取ATRA、ATO 联合髓系白血病化疗方案有一定疗效，但患儿预后欠佳。出血相关死亡，迄今仍是v APL患儿治疗过程中面临的挑战。

Objective

To explore the clinical characteristics of children with variant acute promyelocytic leukemia （v APL），in which intracranial hemorrhage（ICH）in both the first and recurrent episodes，and the nucleophosmin retinoic acid receptor alpha （NPM-RARα）fusion gene positive.

Methods

A female patient with v APL （patient 1）admitted to Chengdu Women's and Children's Central Hospital in December 2020，was chosen as the research subject.The clinical data of patient 1 was analyzed retrospectively，including the clinical manifestations，laboratory and imaging examination results，as well as the treatment process and outcome.Relevant studies of v APL children with NPM-RARαfusion gene positive in domestic and foreign databases were also searched for literature review.The study was in line with the World Medical Association Declaration of Helsinki revised in 2013.The guardian gave informed consent to the diagnosis and treatment process of the child，and signed the informed consent forms for clinical study.

Results

①Patient 1，female，with onset age of 3 years and 9 months old，admitted to hospital with "severe headache，vomiting，abnormal blood routine".After admission to hospital，the blood routine showed abnormal triple systems and abnormal coagulation function.Bone marrow morphology and immunotyping indicated myeloid leukemia，and NPM-RARαfusion gene was found positive，she was diagnosed as v APL.The count of white blood cell（WBC）was ＞100×10⁹/L，therefore，chemotherapy was performed according to the high-risk regimen of acute promyelocytic leukemia （APL）.At the beginning，head CT of patient 1 showed ICH.After induction remission chemotherapy based on all-trans retinoic acid（ATRA）+arsenic trioxide （ATO），the ICH was absorbed and the fusion gene turned negative.During the second cycle of maintenance therapy，the fusion gene turned positive again.After 2 consecutive courses of idarubicin（IDA）combined with cytarabine （Ara-C）chemotherapy，the bone marrow morphology and fusion gene of patient 1 turned negative again.In September 2021，the bone marrow morphology of patient 1 was relapse.During the last hospitalization，ICH occurred again and complicated with cerebral hernia.Patient 1 finally died due to respiratory and circulatory failure.Her total survival time was 9 months.②Literature review：a total of 5 studies on v APL children with positive NPM-RARαfusion gene were retrieved，involving 5 cases （patient 2-6）of v APL children.Analysis of results of case data of 6 children with v APL，including patient 1，showed that three patients （patient 1，3，4）relapsed，one （patient 5）continued complete remission（CR），one （patient 4）had CR again after relapse，and one patient （patient 6）lacked follow-up results.Patient 1 and 2 died.

Conclusions

v APL children with NPM-RARαfusion gene positive is clinically rare.The main treatment method is ATRA and ATO combined with myeloid leukemia chemotherapy regime，which has a certain effect，but the prognosis is still poor.Hemorrhage related death remains a major challenge in the treatment of v APL children.