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移植物中CD34+细胞及T细胞亚型对HLA相合同胞异基因外周血造血干细胞移植预后的影响

The impact of CD34+ calls and T cells subsets in grafts on prognosis of HLA-identical sibling allogeneic peripheral blood stem cell transplantation

摘要目的 探讨移植物中CD34+细胞及T细胞剂量对HLA相合同胞异基因外周血造血干细胞移植(allo-PBSCT)预后的影响.方法 流式细胞术检测移植物中CD34+细胞,CD3+、CD3+CD4+及CD3+CD8+T细胞含量,按患者体重计算出移植物中单个核细胞(MNC),CD34+细胞,CD3+、CD3+CD4+及CD3+CD8+T细胞数量,根据中位数分别将患者分为高剂量组和低剂量组,比较高剂量和低剂量组患者移植后造血重建、移植物抗宿主病(GVHD)、移植相关死亡(TRM)、复发、总体生存(OS)率以及无病生存(DFS)率的发生情况.结果 CD34+细胞高剂量组(34例)移植后中性粒细胞和血小板的恢复速度显著加快(P值均<0.05).CD3+CD4+、CD3+CD8+T细胞高剂量组和相应低剂量组相比,Ⅱ-Ⅳ度aGVHD发生率有增高趋势(P值分别为0.089和0.098).CD3+CD4+及CD3+CD8+T细胞高剂量组和相应低剂量组相比,TRM显著增高(P值均<0.05);多因素分析显示,CD3+CD4+和CD3+CD8+T细胞输注剂量是患者TRM的影响因素(RR分别为13.12和25.90,P值均<0.05).各高剂量组和相应低剂量组比较复发率差异无统计学意义(P值均>0.05).CD3+ CD4+及CD3+CD8+T细胞高剂量组分别和相应低剂量组相比,OS显著降低(P值均<0.05);多因素分析显示,CD3+CD4+和CD3+CD8+T细胞输注剂量是患者OS的影响因素(RR分别为3.71和3.01,P值均<0.05);CD3+CD4+T细胞高剂量组和低剂量组相比,DFS显著降低(P值均<0.05);多因素分析显示,CD3+CD4+T细胞输注剂量(RR=6.91,P=0.011)是患者DFS的影响因素.结论 高剂量CD34+细胞移植可加快移植后造血重建;移植物中高含量的CD3+CD4+及CD3+CD8+T细胞会增加患者TRM,降低OS或DFS.

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abstractsObjective To study the influence of CD34+ and T cells doses in grafts on prognosis after HLA-identieal sibling allngeneic peripheral blood stem cell transplantation (allo-PBSCT).Methods Sixtyfive patients received HLA-identical sibling allo-PBSCT were studied.The numbers of CD34+,CD3+,CD3+ CD4+ and CD3+ CD8+ T cells in the grafts were measured by fluorescence-activated cell sorting (FACS).The doses of MNC,and the above cells in grafts were calculated as per kilogram of recipient' s body weight.The patients were divided into high-dose ( HD ) or low-dose ( LD ) groups according to median dose of those cells,respectively.Hematopoiesis reeonstitution,incidence of graft versus host disease ( GVHD ),transplant-related mortality (TRM) ,overall survival (OS) ,and disease-free survival ( DFS ) were analyzed.Results HD CD34+ cells significantly accelerated nentrophil and platelet reeonstitution (P<0.05).There seems a trend toward increasing incidence of grade Ⅱ~Ⅳ acute GVHD (aGVHD)in HD CD3+ CD4+~ and CD3+ CD8+ T cells groups compared with those LD groups ( P = 0.089 and 0.098,respectively).The TRM rates were significantly higher and OS rates were significantly in HD CD3+ CD4+ and CD3+ CD8+ T cells groups than in LD groups,respectively ( both P < 0.05 ).Multivariate analyses showed that CD3+ CD4+ and CD3+ CD8+ T cells doses in grafts were significant risk factors for TRM [ relative risk (RR) were 13.12 and 25.90,respectively,both P <0.05] and for OS (RR were 3.71 and 3.01,respectively,both P< 0.05).The DFS rate was significantly lower in HD CD3 + CD4+ T cells groups than in LD groups(P<0.05 ).Multivariate analyses showed that CD3+ CD4+ cells dose in grafts was a significant risk factor for DFS (RR=6.91,P=0.011).Conclusions High dose CD34+ cells in grafts significantly accelerate hematopeietic reconstitution.Transfusion of high doses CD3+ CD4 + and CD3+ CD8+ cells increases TRM,but decrease OS or DFS.

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