维奈克拉联合多药化疗治疗初诊未明系列急性白血病的疗效及安全性分析  

Efficacy and safety analysis of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage

作　　者：罗婷[1] 方怡然 刘文洁 孙倩[1] 徐佩 洪鸣[1] 钱思轩[1] Luo Ting;Fang Yiran;Liu Wenjie;Sun Qian;Xu Pei;Hong Ming;Qian Sixuan(Department of Hematology,First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Taizhou People's Hospital,Nanjing Medical University,Taizhou 225300,China)

机构地区：[1]南京医科大学第一附属医院、江苏省人民医院血液科,南京210029 [2]南京医科大学附属泰州人民医院,泰州225300

出　　处：《中华血液学杂志》2025年第2期161-168,共8页Chinese Journal of Hematology

基　　金：国家自然科学基金(82170153)。

摘　　要：目的探讨维奈克拉(VEN)联合多药化疗治疗初诊未明系列急性白血病(ALAL)患者的疗效及安全性。方法回顾性分析2021年6月至2024年7月在江苏省人民医院住院治疗的13例初诊ALAL患者的临床资料,13例患者的初始诱导治疗方案均为以VEN为基础联合多药化疗,其中VAA+P(VEN+阿扎胞苷/地西他滨+阿柔比星+醋酸泼尼松)方案治疗8例,V+IA(VEN+伊达比星+阿糖胞苷)方案治疗5例,FLT3突变患者联合FLT3抑制剂,Ph+患者联合酪氨酸激酶抑制剂治疗。分析患者的总生存(OS)期、无病生存(DFS)期及不良反应。结果根据WHO造血与淋巴组织肿瘤分类第五版关于ALAL的免疫表型定义,13例ALAL患者包括T/髓系混合表型急性白血病(MPAL)4例,B/髓系MPAL 7例,ALAL-非特指型2例。其中4例B/髓系MPAL患者Ph(+),属ALAL特定的基因异常组别。3例患者存在FLT3突变(FLT3-TKD突变1例,FLT3-ITD突变2例)。于巩固治疗前评估VEN联合用药方案的诱导治疗效果:13例患者均获完全缓解(CR)。在随后的巩固治疗过程中,1例患者放弃治疗失访,9例患者进行异基因造血干细胞移植(allo-HSCT),其中4例因移植后并发症死亡,5例无病生存。3例患者(年龄≥70岁)按原方案巩固治疗,其中2例无病生存,1例因白血病中枢神经系统浸润死亡。13例患者的中位OS期未达到,75%位OS期为12.0个月,12个月累积OS率为64.5%,所有患者的中位DFS期未达到,75%位DFS期为8.2个月,12个月累积DFS率为67.1%。VEN联合方案诱导治疗期间及治疗后所有患者均发生3级或4级血液学不良反应,包括中性粒细胞减少和血小板减少。所有患者经初始诱导治疗后造血功能恢复且无致死性大出血发生;无患者出现肿瘤溶解综合征及神经系统不良反应;同时无3级及以上脏器不良反应发生(患者治疗前基础病除外)。结论VEN联合多药化疗治疗初诊ALAL的疗效值得肯定且治疗的相关不良反应可耐受。ObjectiveTo evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage(ALAL).MethodsA retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024.Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy,8 received VAA+P regimen,and 5 received V+IA regimen.Patients with FLT3 mutation were treated with FLT3 inhibitor,and Ph+patients received an additional tyrosine kinase inhibitor.Overall survival(OS),disease-free survival(DFS),and adverse events were analyzed.ResultsAccording to the World Health Organization 5th edition of the classification of hematolymphoid tumors,the immunophenotypes were T/myeloid mixed-phenotype acute leukemia(MPAL)(n=4),B/myeloid MPAL(n=7),and ALAL-not otherwise specified(n=2).Of the seven patients with B/myeloid MPAL,four were Ph+and belonged to the group with specific gene abnormalities of ALAL.Three patients had FLT3 mutation(one with FLT3-TKD mutation and two with FLT3-ITD mutation).Prior to the second course of consolidation therapy,the efficacy of venetoclax induction therapy was evaluated,and a complete response rate of 100%was achieved in 13 patients.In the subsequent consolidation therapy phase,one patient discontinued treatment and was lost to follow-up;nine patients underwent allogeneic hematopoietic stem cell transplantation,four of whom died due to posttransplant complications and five achieved DFS.Of the three patients(≥70 years old)who received consolidation therapy as before,two achieved DFS and one died due to central nervous system leukemia.The median OS time was not reached in 13 patients;the 75th percentile survival time was 12.0 months,with a 12-month cumulative survival rate of 64.5%.The median DFS time was not reached in all patients;the 75th percentile DFS time was 8.2 months,with a 12-month cum

关 键 词：维奈克拉 未明系列急性白血病 抗肿瘤联合化疗方案 

分 类 号：R733.71[医药卫生—肿瘤]