单倍体相合造血干细胞移植治疗35例重型再生障碍性贫血的临床研究

Clinical study of haploidentical allogeneic hematopoietic stem cell transplantation in the treatment of 35 patients with severe aplastic anemia

目的:探讨单倍体相合造血干细胞移植(Haplo-HSCT)治疗重型再生障碍性贫血(SAA)患者的临床疗效及预后影响因素。方法:选择接受Haplo-HSCT治疗的35例SAA患者,其中男25例,女10例,中位年龄24(9~37)岁。预处理方案包含环磷酰胺、氟达拉滨和抗人胸腺淋巴细胞球蛋白,部分患者加用白消安。采用环孢素、短程甲氨蝶呤方案预防移植物抗宿主病(GVHD)。于移植后1、3、6、12、24个月通过短串联重复序列聚合酶链反应(STR-PCR)观察干细胞植入情况,观察终点为患者移植后2年或死亡,分析患者长期生存及移植并发症情况。结果:35例患者中性粒细胞植入与血小板植入的中位时间分别为12(9~22)d、17(7~55)d。其中12例(34.28%)发生Ⅰ~Ⅲ度急性GVHD,4例(11.42%)发生慢性局限型GVHD。中位随访时间为14(0.23~24)个月,至随访结束有3例死亡(脓毒性休克1例,重症肺炎1例,消化道出血1例)。32例患者无病生存,无病生存中位时间为14.5(12~24)个月。存活的患者在移植后不同时间点STR-PCR检测结果均为完全供者嵌合体。结论:在SAA患者Haplo-HSCT中,采用改良预处理方案可获得供者造血干细胞稳定持续植入。

Objective:To explore the clinical therapeutic effect and prognostic factors of haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)in the treatment of severe aplastic anemia(SAA).Method:Thirty-five patients with SAA receiving Haplo-HSCT were enrolled.There were 25 males and 10 females with a median age of 24(9-37)years.Conditioning regimen contained cyclophosphamide,fludarabine and anti-thymocyte globulin.And some patients were treated with busulfan.Cyclosporine and methotrexate were used to prevent graft-versus-host disease(GVHD).The stem cell implantation was observed by STR-PCR at 1,3,6,12 and 24 months after transplantation.The follow-up end point was 2 years after transplantation or death,and the long-term survival and complications of transplantation were analyzed.Result:The median time of neutrophil implantation and platelet implantation in 35 SAA patients was 12(9-22)d and 17(7-55)d,respectively.Among them,12 cases(34.28%)developed acute GVHD ofⅠ-Ⅲdegree,and 4 cases(11.42%)developed chronic limited GVHD.The median follow-up time was 14(0.23-24)months,and 3 patients died(1 case of sepsis,1 case of severe pneumonia,and 1 case of gastrointestinal bleeding)by the end of the follow-up.Thirty-two patients survived free of disease and the median disease-free survival time was 14.5(12 to 24)months.By STR-PCR analysis,the patients survived at different time points after transplantation were complete donor chimeras.Conclusion:In the Haplo-HSCT patients with SAA,our modified conditioning regimen can be used to obtain stable and continuous donor hematopoietic stem cells implantation.