序贯强化预处理后进行移植物抗白血病诱导可预防异基因造血干细胞移植后难治性急性髓系白血病的复发

[Sequential intensified conditioning followed by graft-versus-leukemia induction could prevent relapse of refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

作者信息

Xuan Li, Fan Zhiping, Zhang Yu, Huang Fen, Dai Min, Li Yonghua, Nie Danian, Lin Dongjun, Jiang Qianli, Sun Jing, Xiao Yang, Liu Qifa

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

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出版信息

Zhonghua Yi Xue Za Zhi. 2015 Jun 23;95(24):1915-20.

PMID:26710693

Abstract

OBJECTIVE

To explore the therapeutic effects of sequential intensified conditioning regimen followed by graft-versus-1eukemia (GVL) induction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory advanced acute myeloid leukemia (AML).

METHODS

A total of 72 patients with refractory AML undergoing allo-HSCT from May 2001 to June 2013 were enrolled in this prospective study. Intensified conditioning included fludarabine + cytarabine plus total body irradiation + cyclophosphamide + etoposide. Cyclosporine A was withdrawn rapidly in a stepwise fashion if patients who did not experience acute graft-versus-host disease (aGVHD) at Day + 30 post-transplantation. Donor lymphocytes were infused in patients without grade II or more than grade II aGVHD at Day + 60 post-transplantation.

RESULTS

The median follow-up time was 655 (1-4 200) d post-transplantation. Except for one died of infection and one died of regimen-related toxicity (RRT), the other 70 patients achieved complete remission at the time of neutrophil reconstitution. The mortality of RRT was 1.4% (1/72). The 1-year cumulative incidence of aGVHD and 2-year incidence of chronic GVHD (cGVHD) post-transplantation were 60.7% ± 5.0% and 58.5% ± 4.7%. The 5-year cumulative incidence of relapse post-transplantation was 29.6% ± 6.6%. The 5-year non-relapse mortality was 28.8% ± 6.0%. The 5-year overall and disease-free survival were 51.0% ± 6.5% and 49.9% ± 6.4%. Multivariate analysis revealed that donor lymphocyte infusion, cGVHD and bone marrow blasts at Day 0 were independent prognostic factors for relapse (HR (95% CI): 0.042 (0.007-0.688), 0.009 (0.003-0.345), 3.385 (1.451-7.899)) and survival (HR (95% CI): 0.315 (0.146-0.621), 0.416 (0.200-0.866), 1.332 (1.158-1.533)).

CONCLUSION

The strategy of sequential intensified conditioning followed by GVL induction has an acceptable toxicity profile, and could decrease the relapse rate and improve the survival for refractory AML.

摘要

目的

探讨序贯强化预处理方案联合移植物抗白血病（GVL）诱导在难治性晚期急性髓系白血病（AML）异基因造血干细胞移植（allo-HSCT）中的治疗效果。

方法

本前瞻性研究纳入了2001年5月至2013年6月期间接受allo-HSCT的72例难治性AML患者。强化预处理包括氟达拉滨+阿糖胞苷加全身照射+环磷酰胺+依托泊苷。如果患者在移植后第30天未发生急性移植物抗宿主病（aGVHD），则逐步快速停用环孢素A。在移植后第60天，对无II级或以上aGVHD的患者输注供体淋巴细胞。

结果

移植后中位随访时间为655（1-4200）天。除1例死于感染和1例死于方案相关毒性（RRT）外，其他70例患者在中性粒细胞恢复时达到完全缓解。RRT死亡率为1.4%（1/72）。移植后1年aGVHD累积发生率和2年慢性GVHD（cGVHD）发生率分别为60.7%±5.0%和58.5%±4.7%。移植后5年复发累积发生率为29.6%±6.6%。5年非复发死亡率为28.8%±6.0%。5年总生存率和无病生存率分别为51.0%±6.5%和49.9%±6.4%。多因素分析显示，供体淋巴细胞输注、cGVHD和移植第0天骨髓原始细胞是复发（HR（95%CI）：0.04（0.007-0.688），0.009（0.003-0.345），3.385（1.451-7.899））和生存（HR（95%CI）：0.315（0.146-0.621），0.4（0.200-0.8），1.332（1.158-1.533））的独立预后因素。