Loiseau Pascale, Busson Marc, Balere Marie-Lorraine, Dormoy Anne, Bignon Jean-Denis, Gagne Katia, Gebuhrer Lucette, Dubois Valérie, Jollet Isabelle, Bois Monique, Perrier Pascale, Masson Dominique, Moine Agnès, Absi Léna, Reviron Denis, Lepage Virginia, Tamouza Ryad, Toubert Antoine, Marry Evelyne, Chir Zina, Jouet Jean-Pierre, Blaise Didier, Charron Dominique, Raffoux Colette
Service d'immunologie et histocompatibilité, hôpital Saint-Louis, AP-HP Paris, France.
Biol Blood Marrow Transplant. 2007 Aug;13(8):965-74. doi: 10.1016/j.bbmt.2007.04.010.
HLA matching between the donor and recipient improves the success of unrelated hematopoietic stem cell transplantation (HSCT). Because many patients in need of an unrelated transplant have only donors with mismatch, information is needed to evaluate the limits of HLA mismatching. We examined the association of survival, acute graft-versus-host disease (aGVHD) and relapse with HLA-A, -B, -C, -DRB, -DQB1, and -DPB1 mismatching in 334 patients coming from 12 French transplant centers and who received a non-T cell-depleted bone marrow graft from an unrelated donor. All patients were prepared with the use of myeloablative conditioning regimens. Our analyses demonstrate negative effects of HLA mismatching for either HLA-A, -B, -C, -DRB1, or -DQB1 loci on survival. Multivariate Cox analyses showed that a single mismatch was associated with a significant decrement in survival (P=.046, hazard ratio [HR]=1.41, confidence interval [CI] 95% 1.1-1.98). The presence of multiple mismatches was worse for survival (P=.003, HR=1.91, CI 95% 1.26-2.91) and severe aGVHD (grade III-IV) (P=.002, HR=2.51, CI95% 1.41-4.46). The cumulative incidences of aGVHD and relapse in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with 2, 1, or 0 DPB1 incompatibilities were 63%, 50%, and 51%, and 12%, 27%, and 20%, respectively, but these differences were not statistically significant. Similar differences of aGVHD and relapse, but not statistically significant, were observed in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with DPB1 disparities classified into permissive or nonpermissive mismatches according to Zino's classification based on a hierarchy of the immunogenicity of the HLA-DP molecules. "Missing killer cell immunoglobulin-like receptor (KIR) ligand" evaluated on the presence of HLA-C1, -C2, and Bw4 groups in the recipients was not associated with aGVHD, survival, and relapse in this cohort of non-T cell-depleted HSCT.
供体与受体之间的HLA配型可提高非亲缘造血干细胞移植（HSCT）的成功率。由于许多需要非亲缘移植的患者只有不匹配的供体，因此需要信息来评估HLA不匹配的限度。我们研究了来自12个法国移植中心、接受非T细胞去除的非亲缘供体骨髓移植的334例患者中，HLA - A、- B、- C、- DRB、- DQB1和 - DPB1不匹配与生存、急性移植物抗宿主病（aGVHD）和复发之间的关联。所有患者均采用清髓性预处理方案。我们的分析表明，HLA - A、- B、- C、- DRB1或 - DQB1位点的HLA不匹配对生存有负面影响。多因素Cox分析显示，单个不匹配与生存显著降低相关（P = 0.046，风险比[HR]=1.41，95%置信区间[CI] 1.1 - 1.98）。多个不匹配的存在对生存（P = 0.003，HR = 1.91，95% CI 1.26 - 2.91）和重度aGVHD（III - IV级）（P = 0.002，HR = 2.51，95% CI 1.41 - 4.46）更不利。在HLA - A、- B、- C、- DRB1和 - DQB1相同、DPB1不相容性分别为2个、1个或0个的配对中，aGVHD和复发的累积发生率分别为63%、50%和51%，以及12%、27%和20%，但这些差异无统计学意义。在根据基于HLA - DP分子免疫原性等级的齐诺分类法将DPB1差异分为允许或不允许不匹配的HLA - A、- B、- C、- DRB1和 - DQB1相同配对中，也观察到了aGVHD和复发的类似差异，但无统计学意义。根据受体中HLA - C1、- C2和Bw4组的存在情况评估的“缺失杀伤细胞免疫球蛋白样受体（KIR）配体”与该非T细胞去除的HSCT队列中的aGVHD、生存和复发无关。
