摘要
目的 联合使用脂质体米托蒽醌、维奈克拉、高三尖杉酯碱、奥雷巴替尼治疗儿童难治/复发急性髓系白血病(AML),并评估其疗效和安全性.方法 入组患者为复发AML或存在预后不良相关的分子学异常,如 NUP98重排、FUS∷ERG、CBFA2T3∷GLIS2、FLT3-ITD、-7/7q等,且一线治疗一疗程未缓解的初诊AML患者.脂质体米托蒽醌、维奈克拉、高三尖杉酯碱、奥雷巴替尼(MVHO)联合治疗,每个疗程在骨髓抑制期均给予口服左氧氟沙星及泊沙康唑预防感染.评价一疗程缓解率,客观反应率,无事件生存率和总生存率,并评价该方案的血液学毒性及感染发生率.结果 入组15例患者,MVHO治疗1到2个疗程后,总反应率(CR+CRi+PR)86.7％,1个疗程缓解率(CR+Cri)80％.2例患者因治疗无反应或疾病进展终止该方案.11例接受造血干细胞移植,1例移植后复发.累积复发率为7.7％.8个月的无病生存率和总生存率分别为64.2％和100％.可评价方案安全性的共22个疗程,未发生致死性感染及出血事件.其中5个疗程未发生突破性感染,1个疗程中发生脓毒性休克,3级以上感染发生率78.2％.最常见的4级以上治疗相关副反应为粒细胞缺乏和血小板减少,发生率分别为100％和43.4％.结论 MVHO用于儿童难治/复发AML的治疗安全有效,提示该方案可能可以尝试用于儿童AML的一线治疗.
Abstract
Objective To investigate the efficacy and safety of regimen combined Liposomal Mitoxantrone,Venetoclax,Homoharringtonine,and Olverembatinib(MVHO)in the treatment of refractory or relapsed acute myeloid leukemia.Methods Patients with relapsed or newly diagnosed acute myeloid leukemia with poor prognosis related adverse molecular abnormalities,such as NUP98rearrangements,FUS∷ERG,CBFA2T3∷GLIS2,and del7/7q,who did not achieve complete remission(CR)after one course of first-line chemotherapy were enrolled.Patients received the MVHO regimen,which included liposome mitoxantrone,venetoclax,homoharringtonine,and Olverembatinib.Prophylactic oral levofloxacin and posaconazole were administered from day 8 through whole myelosuppression period of every cycles.One cycle response rate,total response rate,event-free survival(EFS)rate,hematologic toxicity,and infection during this study were evaluated.Results A total of 15 patients were enrolled.After cycle one,the remission rate(CR plus CR with incomplete hematological recovery,CR+Cri)was 80％.The total objective response rate(ORR,CR+Cri+partial response[PR])was 86.7％.A total of 2 patients discontinued because of no response or disease progression,and 11 patients underwent hematopoietic stem cell transplantation(HSCT),after which 1 patient experienced relapse.The cumulative incidence of relapse(CIR)was 7.7％.The 8-month EFS rate was 64.2％(±19％)and the OS rate was 100％.Among 22 cycles of MVHO treatment,there were no associated fatal infections or bleeding events.There were 18 episodes of breakthrough infection occurred in 22 cycles of MVHO.There was 1 case of septic shock,and the incidence of≥grade 3 infection was 78.2％.Common grade 4 treatment-related adverse events were neutropenia,which was experienced by 100％of patients,and grade 4 thrombocytopenia,which was experienced by 43.4％of patients.Conclusions MVHO therapy was effective and reasonably well tolerated in pediatric patients with refractory or relapsed acute myeloid leukemia,suggesting that it may comprise a suitable first-line treatment option for pediatric AML patients.
基金项目
上海交通大学医学院儿科学院儿童急性髓系白血病临床研究中心项目(ELYZX200206)
维普
万方数据