Tiercy J M, Bujan-Lose M, Chapuis B, Gratwohl A, Gmür J, Seger R, Kern M, Morell A, Roosnek E
National Reference Laboratory for Histocompatibility, University Hospital, Geneva, Switzerland.
Bone Marrow Transplant. 2000 Aug;26(4):437-41. doi: 10.1038/sj.bmt.1702529.
Patients transplanted with marrow from an HLA-ABDR serologically matched unrelated donor suffer from more post-transplant complications than those who are transplanted with marrow from an HLA-identical sibling. This is most likely due to either HLA-ABDR incompatibilities not resolved by standard techniques and/or HLA polymorphisms not tested for by routine tissue typing (HLA-Cw,-DQ). By resolving these incompatibilities by molecular techniques combined with the in vitro cytotoxic T lymphocyte precursor frequency (CTLpf) test, we have shown that a high degree of HLA compatibility is associated with increased patient survival. However, higher requirements for HLA matching decrease the number of available donors. We have estimated the probability of finding an HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1 compatible donor based on 104 consecutive unrelated bone marrow donor searches initiated between January 1995 and December 1997, with December 1998 as the endpoint. For 96 patients (92.3%), one or more ABDR-identical donors were listed in the Bone Marrow Donor Worldwide Registry (BMDW). After contacting the registries, we obtained at least one (mean, 5.36; range, 1-20; total, 461) blood sample for 86 patients. A highly compatible donor was identified for 33/86 patients (38.4%), after testing an average number of 4.5 donors/patients (range, 1-13). However, by accepting an HLA-DRB3 or -DQB1 or -Cw incompatibility, this number would be as high as 68.6%. Approximately half of the patients (n = 40) for whom a search had been initiated have been transplanted: 22 patients with a perfectly matched donor, 15 patients with an HLA-DRB3 or -DQB1 or -Cw mismatch and three with other mismatches. The average time needed to identify the most compatible donor was 4 months. Extremely long searches seemed to be less useful, because after testing the first seven, a more compatible donor was seldom found. These results show that even when requirements for compatibility are high, the chances of finding a donor remain considerably low.
接受人类白细胞抗原（HLA）-ABDR血清学匹配的无关供体骨髓移植的患者，比接受HLA完全相同的同胞骨髓移植的患者，术后并发症更多。这很可能是由于标准技术未能解决的HLA-ABDR不相容性和/或常规组织分型（HLA-Cw、-DQ）未检测到的HLA多态性。通过分子技术结合体外细胞毒性T淋巴细胞前体频率（CTLpf）试验解决这些不相容性问题后，我们发现高度的HLA相容性与患者生存率的提高相关。然而，对HLA匹配的更高要求减少了可用供体的数量。我们根据1995年1月至1997年12月启动的104例连续无关骨髓供体搜索，并以1998年12月为终点，估算了找到HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1相容供体的概率。在全球骨髓供体登记处（BMDW）中，96例患者（92.3%）列出了一个或多个ABDR相同的供体。在联系登记处后，我们为86例患者获取了至少一份（平均5.36份；范围1-20份；共461份）血样。在平均检测4.5个供体/患者（范围1-13个）后，为33/86例患者（38.4%）鉴定出高度相容的供体。然而，如果接受HLA-DRB3或-DQB1或-Cw不相容性，这个数字将高达68.6%。大约一半（n = 40）已启动搜索的患者已经接受了移植：22例患者接受了完全匹配的供体，15例患者接受了HLA-DRB3或-DQB1或-Cw不匹配的供体，3例患者接受了其他不匹配的供体。鉴定出最相容供体所需的平均时间为4个月。极长时间的搜索似乎用处不大，因为在检测前七个供体后，很少能找到更相容的供体。这些结果表明，即使对相容性的要求很高，找到供体的机会仍然相当低。
