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非清髓性造血干细胞移植后并发移植物抗宿主病的相关因素分析
引用本文:李庆山,毛平,王顺清,莫文健,张玉平,应逸,邓婷芬.非清髓性造血干细胞移植后并发移植物抗宿主病的相关因素分析[J].中华器官移植杂志,2008,29(8).
作者姓名:李庆山  毛平  王顺清  莫文健  张玉平  应逸  邓婷芬
作者单位:广州市第一人民医院血液科,510180
基金项目:广东省广州市科技计划,广东省科技计划 
摘    要:目的 探讨和分析非清髓性造血干细胞移植(NST)后并发移植物抗宿主病(GVHD)的相关因素.方法 选择34例血液病患者,其中重型再生障碍性贫血(SAA)15例,重型β-地中海贫血(TM)1例,肿瘤性血液病18例;进行无关供者脐带血造血干细胞移植(UCBT)11例,同胞供者骨髓联合外周血干细胞移植7例,外周血造血干细胞移植(PBSCT)16例.移植前采用以抗胸腺细胞球蛋白(ATG)、抗淋巴细胞球蛋白(ALG)或者氟达拉滨强效免疫抑制为基础的非清髓性预处理方案.GVHD的预防采用短程的甲氨蝶呤(MTX)联合环孢素A(CsA).观察非清髓性造血干细胞移植后的临床特点以及急、慢性移植物抗宿主病的发生情况;分析发生慢性移植物抗宿主病(cGVHD)的相关因素.结果 NST的植入率为91.2%.移植后7例肿瘤性血液病患者形成了供、受者造血细胞混合嵌合体(MC),给予供者淋巴细胞输注(DLI)2~9次后,例由MC转变为供者造血细胞完全嵌合体(FDC).随访12(3~96)个月,共发生Ⅰ~Ⅱ度急性移植物抗宿主病(aGVHD)5例,GVHD 15例.经统计学分析,发现年龄大的肿瘤性血液病患者经以ATG为基础的NST后,再给予DLI,其cGVHD的发生率高,且合并感染,对治疗的反应差;而以氟达拉滨为基础的NST患者发生cGVHD后治疗反应较好.移植100 d前后患者分别死亡3例和5例,其中3例死于广泛性cGVHD.结论 患者的年龄大、有合并症、以ATG为基础的预处理方案、肿瘤性血液病是NST后患者并发cGVHD的危险因素.

关 键 词:移植物抗宿主病  造血干细胞移植

Related factor analysis of graft-versus-host disease post nonmyeloablative stem cell transplantation
Abstract:Objective To explore and analyze the related factors of graft-versus-host disease (GVHD) post nonmyeloablative stem cell transplantation (NST) for haematologic diseases.Methods Thirty-four patients including severe aplastic anemia (SAA) (n=15),halassemia major (TM) (n=1) and malignant haematologie diseases (n=18) underwent unrelated umbilical cord blood transplantation (UCBT) (n=11) and sibling donor bone and peripheral blood stem cell transplantation (PBSCT) (n=7) or PBSCT (n=16).Nonmyeloablative conditioning regimens consisted of intensive immunosuppression based on anti-themocyte globulin (ATG),nti-T-lymphocyte globulin (ALG) or fludarabine.GVHD prophylaxis mainly consisted of short course methotrexate and eyclosporine (CsA).Clinical characteristics,nd acute and chronic GVHD were observed.The correlative factors of cGVHD were analyzed.Results Thirty-one (91.2%) patients achieved successful engraftment.In 7 malignant haematologic patients after transplantation,C occurred and after 2 to 9 procedures of DLI,C in 5 cases was turned to FDC.During the median duration of 12 months follow-up,5 patients suffered from acute GVHD of degree Ⅰ to Ⅱ,nd 15 patients from cGVHl3.Statistical analysis showed those patients who received NST-based ATG followed by DLI were characterized with high-rate of cGVHD and infection,nd poor response to treatment.However,n the patients with cGVHD receiving NST-based fludarabine the response to treatment was satisfactory.There were 3 and 5 deaths before and 100 days after transplantation,espectively,nd among them, patients died from cGVHD. Conclusion The risk factors of cGVHD post NST included age complications,ATC-base preconditioning regimen and malignant hematologic diseases.
Keywords:Graft vs host disease  Haematopoietic stem cell transplantation
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