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

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^＋CIM^＋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，CD^3＋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。

Objective To study the influence of CD34^＋ and T cells doses in grafts on prognosis after HLA-identical sibling allogeneic 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 reconstitution, 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 neutrophil and platelet reconstitution （P 〈 0.05 ）. There seems a trend toward increasing incidence of grade Ⅲ - 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 6＋ cells dose in grafts was a significant risk factor for DFS （ RR = 6. 91, P = 0.011 ）. Conehtsions High dose CD34 ^＋ cells in grafts significantly accelerate hematopoietic reconstitution. Transfusion of high doses CD3^ ＋ CD4 ^＋ and CD3 ^＋ CD8^ ＋ cells increases TRM, but decrease OS or DFS.