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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。
AIM To investigate the effect of monoclonal antibodies against basil-agaist T cells and hematopoietic progenitor cells in vitro in vitro on Baleximab (Shuolai) and to investigate the therapeutic effect of the antibody against graft-versus-host disease (GVHD) in HLA-incompatible bone marrow transplantation . Methods Experimental observation divided into two groups. (1) Bareixi group: 72 patients with leukemia received bone marrow transplantation without haploidentical T cell depletion, and Balaixi monoclonal antibody was used to prevent GVHD; (2) Control group: the same as above before November 2000 Fifteen patients with leukemia who underwent bone marrow transplantation did not use basiliximab to prevent GVHD. The ability of basiliximab to react with CTLp was detected by limiting dilution method. The inhibitory effect of basiliximab on granulocyte macrophage-derived progenitor cells was evaluated in semi-solid hematopoietic progenitor cell culture system CFUGM), erythroid progenitor cells (CFUE) and megakaryocyte progenitor cells (CFUMK) colonies. Results All the 72 cases of Baxilb group received hematopoietic reconstitution after the bone marrow transplantation. The direct evidence of bone marrow biopsy showed complete donor hematopoiesis. There was no significant difference compared with the control group. The incidences of acute grade Ⅱ ~ Ⅳ GVHD in Barexide group and control group were 12.5% (9 cases) and 33.3% (5 cases) respectively after transplantation, the difference was statistically significant (P = 0.045). The chronic wide type GVHD incidence, the difference was not statistically significant. Immune cell reconstruction was observed dynamically within 18 months after transplantation. CD3, CD8, CD19, NK cells and CD56 cells recovered to normal levels within 12 months and CD4 cells recovered within 18 months after transplantation. The median follow-up time was 22 months, 42 patients were disease-free and Kaplan Meier survival curves were analyzed. The 2-year disease-free survival was estimated to be 58.3%. There was no significant difference in disease-free survival and recurrence between basilix group and control group. Experiments with donor bone marrow mononuclear cells showed that basiliximab significantly reduced the number of CTLp cells in 10 to 100 fold but did not affect the proliferation of CFUGM, BFUE and CFUMK colonies of normal hematopoietic progenitor cells. Conclusion Baxizumab can selectively limit and reduce allogeneic T cells and thus reduce the incidence of severe acute GVHD. The hematopoietic reconstitution of leukemia patients after bone marrow transplantation is unaffected without increasing the recurrence rate and infection rate.