Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Blood. 2011 Nov 24;118(22):5957-64. doi: 10.1182/blood-2011-06-362111. Epub 2011 Oct 3.
Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft failure in mismatched hematopoietic stem cell transplantation; however, their role in the development of graft failure in matched unrelated donor (MUD) transplantation remains unclear. We hypothesize that DSAs against a mismatched HLA-DPB1 locus is associated with graft failure in this setting. The presence of anti-HLA Abs before transplantation was determined prospectively in 592 MUD transplantation recipients using mixed-screen beads in a solid-phase fluorescent assay. DSA identification was performed using single-Ag beads containing the corresponding donor's HLA-mismatched Ags. Anti-HLA Abs were detected in 116 patients (19.6%), including 20 patients (3.4%) with anti-DPB1 Abs. Overall, graft failure occurred in 19 of 592 patients (3.2%), including 16 of 584 (2.7%) patients without anti-HLA Abs compared with 3 of 8 (37.5%) patients with DSA (P = .0014). In multivariate analysis, DSAs were the only factor highly associated with graft failure (P = .0001; odds ratio = 21.3). Anti-HLA allosensitization was higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in women with 1 (P = .008) and 2 or more pregnancies (P = .0003) than in men. We conclude that the presence of anti-DPB1 DSAs is associated with graft failure in MUD hematopoietic stem cell transplantation.
抗 HLA 供体特异性抗体(DSA)已被报道与不合型造血干细胞移植中的移植物失功有关;然而,其在匹配的无关供体(MUD)移植中导致移植物失功的作用仍不清楚。我们假设针对错配 HLA-DPB1 位点的 DSA 与此种情况下的移植物失功有关。在 592 例 MUD 移植受者中,使用固相荧光检测法中的混合珠,前瞻性地检测了移植前抗 HLA Abs 的存在情况。使用含有相应供体 HLA 错配抗原的单抗原珠进行 DSA 鉴定。在 116 例患者(19.6%)中检测到抗 HLA Abs,包括 20 例(3.4%)抗 DPB1 Abs 患者。总的来说,在 592 例患者中有 19 例(3.2%)发生移植物失功,其中 584 例无抗 HLA Abs 的患者中有 16 例(2.7%)发生移植物失功,而 8 例有 DSA 的患者中有 3 例(37.5%)发生移植物失功(P =.0014)。在多变量分析中,DSA 是唯一与移植物失功高度相关的因素(P =.0001;优势比=21.3)。总的来说,女性的抗 HLA 同种致敏率高于男性(30.8%比 12.1%;P<0.0001),且 1 次(P =.008)和 2 次或以上妊娠(P =.0003)的女性高于男性。我们得出结论,抗 DPB1 DSA 的存在与 MUD 造血干细胞移植中的移植物失功有关。