Tiercy J-M, Stadelmann S, Chapuis B, Gratwohl A, Schanz U, Seger R A, Faveri G Nicoloso de, Kern M, Morell A, Schwabe R, Schneider P
Transplantation Immunology Unit/LNRH, University Hospital, Geneva, Switzerland.
Bone Marrow Transplant. 2003 Sep;32(6):623-7. doi: 10.1038/sj.bmt.1704229.
Unrelated hematopoietic stem cell transplantation (HSCT) is a recognized therapy for hematological diseases and over 8 million HLA-typed donors are ready to donate. Increased international exchanges and rapid requests through the Bone Marrow Donor Worldwide (BMDW) ask for standardized quality assurance. Since no such standards have been established to date, we tested a pilot program in order to evaluate donor availability and quality of HLA typing of the Swiss Registry. The 18500 donors of the registry have been analyzed by serology for HLA-AB and by molecular typing for HLA-DR. Through three successive annual quality control (QC) exercises, a total of 114 donor requests were sent to 13 blood transfusion centers responsible for donor recruitment asking for a blood sample. Donors were randomly selected according to recruitment periods (1988-1993; 1994-1997; 1998-2000), and to homozygosity for HLA-A and/or -B antigens. An additional 80 frozen blood samples from the repository corresponding to the three periods (n=26) and to the 2001 period (n=54) were also included in the HLA study. HLA-AB typings were done by polymerase chain reaction-sequence specific primers (PCR-SSP) and all discrepancies were retyped. The results showed that 79 samples provided by 69.3% of the requested donors were received within 14 days, and 19 samples (16.7%) were received in >14 days. Altogether, an 86% rate of donor availability was observed, independent of the recruitment period. Among the requested donors, 16 (14%) were not available: for medical reasons (two), for personal reasons (eight), for loss (one), and for an unknown reason (five). The HLA-A/B DNA typing results of 166 homozygous and 12 heterozygous blood samples showed that 437/439 (99.5%) of the assigned A/B antigens were correct. However in 36/178 donors (20.2%) an HLA-A or -B antigen had been missed (34 donors) or misassigned (two donors) by serology, with a decreasing discrepancy rate of 30% (1988-1993) to 18.5% in 2001. Assuming that HLA-A or -B homozygotes are found in 10-15% of the donors and that correct assignments have been observed in nearly 100% of the donors, an overall error rate of 4-5% would be expected for the national registry HLA-AB typing. These data show that standardized quality control for donor availability and HLA typing is feasible, and we propose that this model could be applied to the registries participating in bone marrow donor worldwide.
非亲缘造血干细胞移植（HSCT）是治疗血液系统疾病的一种公认疗法，全球有超过800万已进行HLA分型的供者愿意捐献。国际交流的增加以及通过全球骨髓捐献者（BMDW）提出的快速请求，要求有标准化的质量保证。由于迄今为止尚未建立此类标准，我们测试了一个试点项目，以评估瑞士登记处的供者可用性和HLA分型质量。该登记处的18500名供者已通过血清学方法进行HLA-AB分型，并通过分子分型方法进行HLA-DR分型。通过连续三次年度质量控制（QC）活动，总共向负责供者招募的13个输血中心发送了114份供者请求，要求提供血样。根据招募时期（1988 - 1993年；1994 - 1997年；1998 - 2000年）以及HLA-A和/或 -B抗原的纯合性随机选择供者。另外，来自对应于这三个时期（n = 26）和2001年时期（n = 54）的储存库的80份冷冻血样也被纳入HLA研究。HLA-AB分型通过聚合酶链反应 - 序列特异性引物（PCR-SSP）进行，所有差异均重新分型。结果显示，69.3%的被请求供者提供的79份样本在14天内收到，19份样本（16.7%）在超过14天后收到。总体而言，观察到供者可用性率为86%，与招募时期无关。在被请求的供者中，16名（14%）不可用：因医疗原因（2名）、个人原因（8名）、丢失（1名）以及原因不明（5名）。166份纯合和12份杂合血样的HLA-A/B DNA分型结果显示，指定的A/B抗原中有437/439（99.5%）是正确的。然而，在36/178名供者（20.2%）中，血清学方法遗漏了（34名供者）或错误指定了（2名供者）一个HLA-A或 -B抗原，差异率从1988 - 1993年的30%下降到2001年的18.5%。假设在10 - 15%的供者中发现HLA-A或 -B纯合子，并且在几乎100%的供者中观察到正确的分型，那么国家登记处HLA-AB分型的总体错误率预计为4 - 5%。这些数据表明，对供者可用性和HLA分型进行标准化质量控制是可行的，我们建议该模式可应用于参与全球骨髓捐献者登记的机构。
