Beelen D W, Ottinger H D, Elmaagacli A, Scheulen B, Basu O, Kremens B, Havers W, Grosse-Wilde H, Schaefer U W
Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany.
Blood. 1997 Dec 15;90(12):4725-35.
The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts <500/microL (13 v 17 days) or <1,000/microL (16 v 19 days) and unsupported platelet counts <20,000/microL (11 v 15 days) or <50, 000/microL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% +/- 10% but ranged between 86% +/- 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% +/- 9% in recipients of GVHD-matched transplants (P < .003). The 2-year survival estimates were 54% +/- 10% for patients with alternative family donors and 65% +/- 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.
在血液系统恶性肿瘤患者中，前瞻性比较了来自基因型人类白细胞抗原（HLA）相同的同胞（n = 36）或其他家族供者（n = 24）的重组人粒细胞集落刺激因子动员的异基因外周血干细胞（PBSC）移植后的临床结果、细胞免疫重建和造血嵌合情况。34例可评估的HLA相同同胞供者患者中的32例以及所有其他家族供者患者均实现了三系造血植入。两组患者达到外周血中性粒细胞计数<500/μL（13天对17天）或<1000/μL（16天对19天）以及无支持的血小板计数<20000/μL（11天对15天）或<50000/μL（19天对24天）的中位时间间隔，以及红细胞和血小板输注需求均无显著差异。60例研究患者中Ⅱ至Ⅳ级急性移植物抗宿主病（GVHD）的累积概率为48%±10%，但在供者至少有一个HLA - A、B、DR、DQ、DP抗原与急性GVHD方向不一致的患者中为86%±12%，在GVHD匹配移植受者中为25%±9%（P < 0.003）。其他家族供者患者的2年生存率估计为54%±10%，HLA相同同胞供者患者为65%±9%。多因素分析确定移植前疾病分期、患者年龄和急性GVHD是总体生存和无病生存的独立预测因素，而仅其他家族供者对这些临床终点没有不良影响。移植后第一年每月对外周血T辅助细胞亚群、B细胞和单核细胞进行监测，结果显示两组患者的免疫细胞重建过程几乎相同。此外，在移植后12个月内，通过性染色体和可变串联重复序列分析，两组患者中完全嵌合患者的比例没有差异。总之，对于缺乏HLA相同同胞供者的患者，来自其他家族供者的PBSC是异基因移植的一个有吸引力的来源，应与来自其他家族供者的骨髓移植进行进一步比较评估。
