Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation
Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation
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DOI：
10.1182/blood-2014-05-576041
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发表时间：
2014-10-16
期刊：
影响因子：
20.3
通讯作者：
Anasetti, Claudio
中科院分区：
文献类型：
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作者：
Pidala, Joseph;Lee, Stephanie J.;Anasetti, Claudio
我们研究了目前非亲属供体异体造血细胞移植（HCT）的结果，以确定供体-受体HLA匹配的临床意义。在1999年至2011年间首次因急性髓性白血病、急性淋巴细胞白血病、慢性髓性白血病和骨髓增生异常综合征接受骨髓清除无关骨髓或外周血HCT的成人和儿童患者被纳入研究。所有人都有HLA-A， -B， -C和-DRB1的高分辨率分型。在总数（n=8003）中，8/8 （n=5449）、7/8 （n=2071）和6/8 （n=483）匹配。HLA不匹配（6-7/8）与HLA匹配病例（8/8）相比，显著增加了II至IV级和III至IV级急性移植物抗宿主病（GVHD）、慢性GVHD、移植相关死亡率（TRM）和总死亡率。不匹配的类型（等位基因/抗原）和位点（HLA-A、-B、-C和-DRB1）与总死亡率无关。在8/8例匹配病例中，HLA-DPB1和-DQB1错配导致急性GVHD加重，HLA-DPB1错配降低复发率。非容许型HLA-DPB1等位基因错配与容许型HLA-DPB1错配或HLA-DPB1匹配相比具有更高的TRM，在8/8（和10/10）匹配病例中，与容许型HLA-DPB1错配相比，总死亡率增加。HLA-A, -B， -C和-DRB1的完全匹配是最佳非亲属供体HCT存活所必需的，并且建议避免HLA-DPB1不匹配，否则hla匹配对。
We examined current outcomes of unrelated donor allogeneic hematopoietic cell transplantation (HCT) to determine the clinical implications of donor-recipient HLA matching. Adult and pediatric patients who had first undergone myeloablative-unrelated bone marrow or peripheral blood HCT for acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome between 1999 and 2011 were included. All had high-resolution typing for HLA-A, -B, -C, and -DRB1. Of the total (n=8003), caseswere 8/8 (n=5449), 7/8 (n=2071), or 6/8 (n=483) matched. HLA mismatch (6-7/8) conferred significantly increased risk for grades II to IV and III to IV acute graft vs host disease (GVHD), chronic GVHD, transplant-related mortality (TRM), and overall mortality compared with HLA-matched cases (8/8). Type (allele/antigen) and locus (HLA-A, -B, -C, and -DRB1) of mismatch were not associated with overall mortality. Among 8/8 matched cases, HLA-DPB1 and -DQB1 mismatch resulted in increased acute GVHD, and HLA-DPB1 mismatch had decreased relapse. Nonpermissive HLA-DPB1 allele mismatch was associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 8/8 (and 10/10) matched cases. Full matching at HLA-A, -B, -C, and -DRB1 is required for optimal unrelated donor HCT survival, and avoidance of nonpermissive HLA-DPB1 mismatches in otherwise HLA-matched pairs is indicated.