巴利昔单克隆抗体预防HLA不相合骨髓移植中移植物抗宿主病  

Basiliximab for prophylaxis of graft-versus-host disease in mismatched bone marrow transplantation

作　　者：纪树荃[1] 陈惠仁[1] 王恒湘[1] 阎洪敏[1] 刘静[1] 薛梅[1] 朱培瑜[1] 肖名华[1] 

机构地区：[1]解放军空军总医院血液科,北京100036

出　　处：《中华器官移植杂志》2005年第10期606-609,共4页Chinese Journal of Organ Transplantation

基　　金：解放军总后勤部卫生部高新技术资助项目

摘　　要：目的研究巴利昔(商品名:舒莱)单克隆抗体体外对异基因反应T细胞和造血祖细胞的作用;探讨该抗体在预防HLA不相合骨髓移植中移植物抗宿主病(GVHD)的疗效。方法实验观察分两组。(1)巴利昔组:白血病患者72例,接受单倍型相合未去T细胞的骨髓移植,用巴利昔单克隆抗体预防GVHD;(2)对照组:2000年11月前进行上述相同骨髓移植的白血病患者15例,未用巴利昔单克隆抗体预防GVHD。用有限稀释方法检测巴利昔单抗对细胞毒介导的靶细胞前体(CTLp)的反应能力,在半固体造血祖细胞培养体系中检测巴利昔单抗对粒巨噬系祖细胞(CFUGM)、红系祖细胞(CFUE)及巨核系祖细胞(CFUMK)集落增殖的影响。结果巴利昔组72例骨髓移植后均取得造血重建,骨髓植活直接证据检测证实为完全供者造血,与对照组比较,差异无统计学意义。巴利昔组和对照组移植后急性Ⅱ～Ⅳ度GVHD发生率分别为12.5%(9例)和33.3%(5例),差异有统计学意义(P=0.045);两组的慢性广泛型GVHD发生率比较,差异无统计学意义。移植后18个月内动态观察免疫细胞重建,CD3、CD8、CD19、NK细胞及CD56细胞在12个月内可恢复至正常水平,CD4细胞在移植后18个月内恢复。随访中位数时间22个月,无病生存42例,KaplanMeier生存曲线分析,估计2年无病生存达58.3%。巴利昔组和对照组比较,无病存活和复发率差异无统计学意义。采用供者骨髓单个核细胞进行实验,显示巴利昔单抗能明显降低CTLp细胞生成,降低的数量在10～100倍,但不影响正常造血祖细胞CFUGM、BFUE和CFUMK集落的增殖。结论巴利昔单抗可选择性的限制和减少异基因反应T细胞,从而减少严重急性GVHD的发生率;白血病患者骨髓移植后造血重建未受影响,不增加复发率和感染率。Objective To investigate the effects of Basiliximab on alloreactive T lymphocytes precursors, hematopoietic progenitor cells by ex vivo assay and prophylaxis of graft-versus-host disease （GVHD） in mismatched bone marrow transplantation. Methods Two groups were set up： （1） Basiliximab group including 72 leukemia patients subject to haploidentical bone marrow transplantation （BMT） with Basiliximab for prophylaxis of GVHD without ex vivo T-cell depletion. （2） Control group having 15 patients receiving the same regimen before Nov. 2000, without Basiliximab for GVHD prophylaxis. Limiting-dilution method was used to determine the effect of Basiliximab on reactivity of cytotoxic T lymphocyte precursors （CTLP）. In the semi-solid hematopoietic culture system, the effect of Basiliximab on the colony proliferation of CFU-GM, BFU-E and CFU-Meg was measured. Results In Basiliximab group, 72 patients established trilineage with full donor hematopoietic reconstitution. Engraftment rate showed no statistical difference between the two groups. The incidence of grade Ⅱ-Ⅳ GVHD was 12. 5 % （9 cases） in Basiliximab group and 33.3 % （5 cases） in control group respectively （P〈0. 05）. The extensive chronic GVHD had no statistical difference between two groups. Immune reconstitution was achieved in 18 months, blood CD3, CD8, CD19 and CD56 cells were returned to normal levels in 12 months, and CD4 cells became normal in 18 months after transplantation. The median follow-up duration was 22 months and there were 42 patients with disease-free survival. Kaplan-Meler life curve revealed the 2-year disease-free survival rate was 58. 3 %. There was no statistically significant difference in the disease-free survival and rate of relapse between the two groups. The experiment with donor mononuclear cells of bone marrow showed Basiliximab significantly reduced the number and frequency of CTLP by 10-fold to 100-fold, but had no effect on the colony proliferation of normal hematopoietic cells of CFU-GM, BFU-E a

关 键 词：抗体 单克隆 骨髓移植 移植物抗宿主病 单克隆抗体 HLA不相合 预防 GVHD发生率 造血祖细胞 粒-巨噬系祖细胞 CFU-MK 

分 类 号：R733.71[医药卫生—肿瘤]