FLAG方案治疗难治复发急性髓系白血病的临床研究

Clinic Outcome of FLAG Regimen treating Patients with Refractory and Relapse Acute Myeloid Leukemia

目的:通过回顾性分析FLAG治疗方案对初治诱导失败和难治复发急性髓系白血病(acute myeloid leukemia,AML)患者的疗效及患者预后,探讨患者的治疗选择及治疗时机。方法:对2006年7月至2013年7月住院治疗的38名初治诱导失效及难治/反复AML患者进行了回顾性分析。38例患者的中位年龄40.5(13-69)岁,根据疾病状态分为初次诱导失败组、再次诱导失败组、早期复发组、晚期复发组;根据危险分层分为预后良好、预后中等和预后不良组。结果:22例达CR(complete remission),5例达PR(partial remission),CR率为57.9%,总有效率OR(overall response)为71.1%。初次诱导失败组的CR率(12/16,75%)高于再次诱导失败组(3/7,42.9%)和晚期复发组(6/12,50%),预后较好组和预后中等组的CR率(5/8,62.5%,16/26,61.5%)高于预后不良组(1/4,25%)。危险分层与CR有关(P=0.03)[OR 25.9,(95%CI 1.2-545.4)],预后中等是CR的有利因素。在22例CR患者中,12例行造血干细胞移植,其中6例存活,另10例以大剂量阿糖胞苷和其它方案进行巩固治疗。总生存期为25月。单因素分析FLAG方案治疗反应与生存相关[HR=0.246,CR vs NR(95%CI 0.07-0.79)],(P=0.03),CR组和PR组2年累积生存率分别为62%和48%。预后良好、预后中等和预后不良组18个月累积生存率为73%、52%和36%(P=0.17);初次诱导失败组和再次诱导失败组18月累积生存率分别为65%和32%(P=0.19)。结论:FLAG方案治疗难治复发AML患者疗效确切,通过化疗获得缓解的患者可进一步采用造血干细胞移植或其它方案以巩固化疗效果和延长生存。

Objective:To evaluate the efficacy of FLAG regimen for treating patients with refractory/relaspse AML and their progonistic factors.Methods:The 38 patients with median age 40.5(range 13-69) were treated with FLAG regimen from July 2006 to July 2013 in hospital.According to disease status,all the patiens were divided into 4 different groups:early relapse group(3 patients),late relapse group(12 patients),first induction failure group(16 patients) and second induction failure group(7 patients);meanwhile,based on risk status,all above- mentioned patients were stratified into better(8 patients),intermediate(26 patients) and poor(4 patients) groups,respectively.Results:Twenty two cases achieved complete remission,5 cases achieved partial remission among 38 patients.The complete remission(CR) rate was 57.9%and the overall response(OR) rate was 71.7%.The CR rate was higher in first induction failure group(12/16,75%) than that in second induction failure group(3/7,42.9%) and late relapse group(6/12,50%).In better group and intermediate group,the CR rates(5/8,62.5%;16/26,61.5%) were higher than that in poor group(1/4,25%).The risk status was associated with the CR rate(P=0.03)[OR=25.9(95%CI 1.2-545.4)].The intermediate risk was favorable factor to CR.Out of 22 patients with CR,12 patients received allogenetic hematopoietic stem cell transplantation(allo-HSCT) and 10 patients received large dose of cytarabine or other regimens as consolidation treatments,6 patients who accepted allo-HSCT are still alive.The overall survival(OS) was25 months.The univariate analyses showed that the response to FLAG was accociated with OS[HR =0.246,CR vs NR(95%CI 0.07-0.79) P=0.03].The 2-year cumulative survial rates in CR group and PR group were 62%and 48%,respectively.The 18-month cumulative survival rate was 73%in better group,52%in intermediate group,36%in poor group(P =0.17);and 65%in first induction failure group and 32%in second induction failure group(P = 0.19).Conclusion:The efficacy of FLAG regimen has been confirmed to be effective for patients with refractory and relapse AML.The patients who achieved remission could acquire benefit from following HSCT or other consolidation chemotherapy,and their survials could be improved.