经典全身照射联合FLAG方案预处理治疗难治／复发白血病患者的疗效分析

Curative efficacy of allogeneic hematopoietic stem cell transplantation using conditioning regimen of TBI/FLAG for refractory or relapsed leukemia patients

目的 探讨以经典全身放疗＋氟达拉滨联合中剂量阿糖胞苷、重组人粒细胞集落刺激因子（TBI＋ FLAG）预处理方案进行异基因造血干细胞移植（allo-HSCT）治疗难治/复发白血病患者的安全性及疗效.方法 回顾分析2012年5月至2015年12月收治的47例难治/复发白血病患者,其中急性淋巴细胞白血病14例,急性髓性白血病31例,慢性粒细胞白血病急变期2例,移植前患者骨髓均未达缓解,原始细胞比例为10％ ～98％,预处理均采用以TBI＋ FLAG为主方案.采用Kaplan Meier曲线分析移植物抗宿主病（GVHD）的累积发生率、累积复发率、总存活率（OS）和无病存活（DFS）率.结果 47患者中除1例预处理的的过程中合并感染细胞未植活外,46例患者均顺利植活,白细胞植活的时间中位数为17（11～25）天,血小板植活的时间中位数为21（11～70）天.急性GVHD的累积发生率为（62.3±7.3）％,其中Ⅱ～Ⅳ和Ⅲ～Ⅳ度的累积发生率分别为51.1％和28.4％,可评估的44例患者中,24例患者发生慢性GVHD,累积发生率为（77.1±11.2）％.移植后28天评估骨髓,46例患者均达完全缓解,经DNA检测证实均为完全供者嵌合状态.患者随访时间中位数为12（1～44）个月,25例患者存活（53.19％,25/47）,13例复发（27.65％,13/47）.HSCT后1年的OS为47.9％,DFS为45.5％.结论 以TBI＋ FLAG为主的预处理方案治疗难治/复发白血病是安全、有效的,移植后复发仍然是难治/复发白血病患者面临的主要风险,需要进一步探索预防移植后复发的方法.

Objective To explore the safety and efficacy of allogeneic hematopoietic stem cell transplantation （allo-HSCT） in refractory or relapsed leukemia patients undergoing total body irradiation and FLAG regimen consisting of fludarabine,cytarabine,granulocyte colony stimulating factor （TBI/FLAG）.Methods Forty-seven cases of refractory or relapsed leukemia treated in our hospital between May 2012 and December 2015 were analyzed retrospectively,including 14 cases of acute lymphoblastic leukemia,31 cases of acute myeloid leukemia,2 cases of acute transformation of chronic myelocytic leukemia.All patients did not achieve remission before bone marrow transplantation.The proportion of blast cells was 10%-98%.The TBI/FLAG was the main conditioning regimen.Kaplan-meier curve was used to analyze the cumulative incidence of GVHD,cumulative recurrence rate,overall survival rate （OS） and disease-free survival rate （DFS）.Results Of 47 cases,there was only one patient with infection during the preconditioning and the cell engraftment was not successful,and the rest 46 patients were successfully engrafted.The median time of leukocyte engraftment was 17 （11-25） days,and the median time of platelet engraftment was 21 （11-70） days.The cumulative incidence of acute GVHD was （62.3 ± 7.3）%,including 51.1% and 28.4% in Ⅱ and Ⅲ-Ⅳ grade respectively.Twenty-four patients suffered chronic GVHD in 44 assessable patients,and the cumulative incidence was （77.1 ± 11.2）%.The bone marrow was assessed 28 days after transplantation,and the results showed that 46 patients achieved complete remission,and DNA test confirmed complete donor chimerism.The median follow-up time was 12 （1-44） months,25 patients survived （53.19%,25/47）,and 13 relapsed （27.65%,13/47）.The 1-yearOS and DFS was 47.9% and 45.5% after transplantation.Conclusion TBI/FLAG-based regimen is safe and effective for refractory or relapsed leukemia,and the major risk still is relapse for refractory or relapsed leukemia patients after transplantation.The method of preventing recurrence needs to be further explored.