维奈克拉、地西他滨及改良HA方案联合供者淋巴细胞输注治疗儿童造血干细胞移植后复发AML/MDS的安全性和有效性研究  

Efficacy and safety of venetoclax combined with decitabine,modified HA regimen and DLI in the treatment of relapsed pediatric AML/MDS after allogeneic hematopoietic stem cell transplantation

作　　者：张枫 王慧芳 胡冠华[1] 锁盼[1] 柏露[1] 王昱[1] 张晓辉[1] 黄晓军[1] 程翼飞[1] Zhang Feng;Wang Huifang;Hu Guanhua;Suo Pan;Bai Lu;Wang Yu;Zhang Xiaohui;Huang Xiaojun;Cheng Yifei(Peking University People's Hospital,Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Beijing 100044,China)

机构地区：[1]北京大学人民医院,北京大学血液病研究所,国家血液系统疾病临床医学研究中心,造血干细胞移植北京市重点实验室,北京100044

出　　处：《中华血液学杂志》2024年第9期832-837,共6页Chinese Journal of Hematology

摘　　要：目的探究急性髓系白血病(AML)/骨髓增生异常综合征(MDS)患儿异基因造血干细胞移植(allo-HSCT)后分子学复发及血液学复发者,应用维奈克拉联合地西他滨、阿糖胞苷、高三尖杉酯碱化疗及供者淋巴细胞输注(DLI)的挽救性治疗的有效性和安全性。方法纳入2021年1月1日至2023年6月1日北京大学人民医院血液科收治的儿童AML/MDS allo-HSCT后血液学复发/分子学复发患者29例,应用维奈克拉联合地西他滨、改良HA方案进行化疗和DLI回输,评估治疗反应和不良反应。结果所有患儿1个疗程总体反应率(ORR)为75.8%,其中血液学复发组完全缓解(CR)率88.9%(8/9),分子学复发组MRD转阴率61.1%(11/18)。3级及以上粒细胞缺乏、贫血、血小板减少发生率分别为100%、82.7%、100%。所有患儿中位粒细胞缺乏期为15 d。DLI后11.1%患儿发生Ⅲ~Ⅳ度急性移植物抗宿主病(GVHD),7.4%的患儿发生中度及以上慢性GVHD。单因素分析中,allo-HSCT时单个核细胞(MNC)回输量<10×108/kg及100 d内复发对ORR有显著影响。所有患儿中位随访406 d,1年总生存(OS)率为65%,其中有治疗反应组和无治疗反应组1年OS率分别为71%和57%,差异无统计学意义(P=0.164)。结论以地西他滨、维奈克拉、高三尖杉酯碱及阿糖胞苷为基础的化疗方案联合DLI在儿童AML/MDS allo-HSCT后复发的挽救性治疗中显示出较好的反应,但达到缓解后应尽快桥接移植以获得长期生存。ObjectiveTo investigate the efficacy and safety of venetoclax combined with the decitabine,cytarabine,and homoharringtonine(HHT)regimen and donor lymphocyte infusion(DLI)for the preventive and salvage therapy of pediatric acute myeloid leukemia(AML)/myelodysplastic syndrome(MDS)after allogeneic hematopoietic stem cell transplantation(HSCT).MethodsA total of 29 relapsed pediatric/minimal residual disease-positive AML after HSCT were recruited at the Peking University Institute of Hematology from January 1,2021,to June 1,2023.They were treated with the above combination regimen and administered with DLI after 24-48 hours at the end of chemotherapy,and the treatment response and adverse reactions were regularly assessed.ResultsThe overall response rate(ORR)was 75.8%,CR rate was 88.9%(8/9)in the hematologic relapse group,and MRD negativity rate was 61.1%(11/18)in the MRD-positive group.The incidence of agranulocytosis,anemia,and thrombocytopenia with a classification above grade 3 were 100%,82.7%,and 100%,respectively.The median time of the granulocyte deficiency period was 15 days.Acute graft-versus-host diseases(aGVHD)with a classification of gradesⅢ-Ⅳoccurred in 11.1%of the patients after DLI,while moderate or severe cGVHD occurred in 7.4%of the patients.The single risk factor for ORR was MNC counts of less than 10×108/kg,and the relapse occurred within 100 days.At a median follow-up of 406 days,the 1-year OS was 65%,and the 1-year OS was 57%in the group with no reaction(P=0.164)compared with 71%in the group who had an overall reaction.ConclusionThe combined regimen based on the DAC,VEN,and modified HA regimen showed a high response rate in the salvage therapy for pediatric AML after the relapse of HSCT.However,bridging to transplantation should be performed immediately after remission to result in a long survival rate.

关 键 词：造血干细胞移植 复发 儿童 白血病 挽救性化疗 

分 类 号：R457.7[医药卫生—治疗学] R733.71[医药卫生—临床医学]