超强预处理allo-HSCT联合GVL诱导策略治疗难治性急性淋巴细胞白血病74例

摘要

Objective To explore the safety and effectiveness of sequential intensified conditioning regimen combined with graft-versus-1eukemia (GVL) induction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory advanced acute lymphoblastic leukemia (ALL).Methods A total of 74 patients with refractory ALL,undergoing allo-HSCT from Jan.2005 to Dec.2014,were enrolled in this study.Intensified conditioning was:fludarabine + cytarabine plus total body irradiation + cyclophosphamide + etoposide.Cyclosporine A was withdrawn rapidly in a stepwise fashion if patients did not experience acute graft-versus-host disease (aGVHD) by day + 30 post-transplantation.Donor lymphocytes were infused in patients without grade Ⅱ or more than grade Ⅱ aGVHD by day + 60 post-transplantation.Results Except for one who died of infection and one who died of regimen-related toxicity (RRT),the remaining 72 patients achieved complete remission at the time of neutrophil reconstitution.The mortality of RRTs was 1.4％ (1/74).The 5-year cumulative incidence of relapse post-transplantation was (29.2 ± 6.1)％.The 5-year non-relapse mortality was (30.4 ± 5.6) ％.The 5-yesr overall and disease-free survival was (49.5 ± 5.9) ％ and (48.2 ± 5.9) ％ respectively.The 5-year leukemia relapse rate,overall and disease-free survival were similar between patients with B-cell ALL and T-cell ALL (P =0.929,P =0.652,P =0.691).Multivariate analysis revealed that donor lymphocyte infusion,chronic GVHD and bone marrow blasts on day 0 were independent prognostic factors for relapse and survival (P =0.043,P=0.026,P＜0.001;P=0.045,P=0.029,P＜0.001).Conclusion The strategy of sequential intensified conditioning combined with GVL induction could decrease the relapse rate and improve the survival for refractory ALL.%目的 探讨超强预处理异基因造血干细胞移植(allo-HSCT)联合移植物抗白血病(GVL)诱导策略治疗难治性未缓解急性淋巴细胞白血病(ALL)的安全性和有效性.方法 将2005年1月至2014年12月行allo-HSCT的74例难治性ALL患者纳入此研究.序贯超强预处理方案为氟达拉滨+阿糖胞苷+全身放疗+环磷酰胺+依托泊苷.GVL诱导策略包括:移植后第30天对未发生急性移植物抗宿主病(GVHD)者给予快速递减免疫抑制剂,至第60天未发生Ⅱ度或以上急性GVHD者给予供者淋巴细胞输注(DLI).结果 除2例在移植后1周内分别死于感染和预处理相关毒性外,其他受者均在粒系重建时获得完全缓解.预处理相关致死率为1.4％(1/74).白血病的5年复发率为(29.2±6.1)％,5年非复发死亡率为(30.4±5.6)％,5年总存活率(OS)和无病存活率(DFS)为(49.5±5.9)％和(48.2±5.9)％.B淋巴细胞ALL和T淋巴细胞ALL患者的5年复发率、OS和DFS无显著差异(P=0.929、P=0.652和P=0.691).DLI、慢性GVHD和移植0天骨髓幼稚细胞是移植后复发和生存的独立预后因素(P=0.043、P=0.026及P＜0.001;P=0.045、P=0.029及P＜0.001).结论序贯超强预处理allo-HSCT联合GVL诱导策略能降低难治性ALL复发率和提高受者的存活率.