去甲基化药物预防儿童急性白血病造血干细胞移植后复发的安全性及耐受性分析

The safety and tolerability of demethylation drugs in preventing relapse of pediatric acute leukemia after hematopoietic stem cell transplantation

目的探讨儿童急性白血病行异基因造血干细胞移植后应用去甲基化药物(HMAs)预防白血病复发的安全性、耐受性。方法回顾性分析2019年12月—2022年1月20例白血病患儿在移植后接受HMAs预防性治疗的临床资料,10例予地西他滨,10例予阿扎胞苷,每例在可耐受状态下完成4~6个疗程后进入随访观察。末次随访时间是2022年10月,分析HMAs治疗期间患儿的耐受情况,比较3~4级不良事件(AE)与不同HMAs、同种药物不同剂量的相关性。结果20例中15例完成了4~6个疗程HMAs治疗方案。在完成的80个HMAs疗程中,共发生37例次3~4级AE:中性粒细胞计数减少27例次;血小板减少2例、贫血1例;肝功能异常2例;感染性疾病5例。阿扎胞苷组发生3~4级AE显著低于地西他滨组(P<0.001)。预防复发的疗效显示20例患儿除1例髓外复发外,余19例均无复发。结论HMAs在造血干细胞移植后预防性应用安全性及耐受性良好,发生3~4级AE与HMAs的种类有明显相关性,但与其剂量无明显相关性。

Objective To investigate the safety and tolerability of demethylation drugs for the prevention of leukemia recurrence after allogeneic hematopoietic stem cell transplantation in children with acute leukemia.Methods Retrospective analysis was conducted on the clinical data of 20 children with acute leukemia who received prophylactic demethylation therapy after allo-HSCT from December 2019 to January 2022.10 patients were treated with decitabine,10 patients were treated with azacitidine,and each patient was followed up after completing 4-6 cycles in a tolerant state.The last follow-up was conducted in October 2022 and then we analyze tolerability during demethylation therapy,compare the associations of grade 3-4 adverse events(AE)with different demethylation drugs,and the same drug but different doses.Results 15 of the 20 enrolled patients completed 4-6 cycles.In the 80 completed courses,a total of 37 case times of grade 3-4 AE occurred:27 case times of neutrophil count decreased,2 cases of thrombocytopenia and 1 case of anemia,2 cases of abnormal liver function,5 cases of infectious disease.The incidence of grade 3-4 AE with AZA is significantly lower than that with DAC.The efficacy of relapse prevention showed that there was no relapse in 19 cases except for 1 case of extramedullary relapse.Conclusions The prophylactic application of demethylation drugs after allo-HSCT is safe and well tolerated.There is significant correlation between the occurrence of grade 3-4 AE and the king of demethylation drugs,but not with the dose.