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.