Histocompatibility and Immunogenetics Laboratory, Gartnavel General Hospital, Glasgow, UK.
Blood and Marrow Stem Cell Transplant Unit, Beatson, West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK.
Bone Marrow Transplant. 2014 May;49(5):657-63. doi: 10.1038/bmt.2014.8. Epub 2014 Feb 17.
The effect on survival of including HLA-DPB1 in a 12-allele matching strategy was retrospectively evaluated in 130 patients with acute leukaemia and myelodysplasia undergoing T-cell-depleted PBSC transplantation using unrelated donors. Patients received alemtuzumab in vivo T-cell depletion as part of a myeloablative (MA; n=61) or reduced-intensity conditioning regimen (n=69). No difference in OS was seen with single-locus mismatching (mm) when 10 conventional alleles (HLA-A, B, C, DRB1 and DQB1) were considered. However, the addition of HLA-DPB1 matching data proved highly discriminatory. Mismatches were identified in 87% of patients previously considered fully matched (1DPmm=49pts: 2DPmm=28pts), and in the 9/10 group 22 patients were reclassified as double and 16 as triple mismatches. In 10/10 transplants, there was a distinct trend to poorer OS with double DPB1 mm. If all 12 loci were considered, 98% of single mm were at HLA-DPB1. Furthermore, cumulative mm at two or more loci was associated with significantly poorer 3-year OS (34% vs 48%, P=0.013: hazard ratio 1.8 (95% confidence interval 1.14-3.06; P=0.017), although his detrimental effect was only apparent using MA conditioning, in which reduced OS was associated with increased chronic GVHD (61% vs 16%, P=0.018) and nonrelapse mortality (30% vs 9%, P=0.039).
在 130 例接受非血缘供者去T 细胞 PBSC 移植的急性白血病和骨髓增生异常综合征患者中,回顾性评价了包含 HLA-DPB1 的 12 等位基因匹配策略对生存的影响。患者接受了 Alemtuzumab 体内 T 细胞耗竭,作为清髓(MA;n=61)或强度降低的预处理方案(n=69)的一部分。当考虑 10 个常规等位基因(HLA-A、B、C、DRB1 和 DQB1)时,单一位点不匹配(mm)在 OS 方面没有差异。然而,添加 HLA-DPB1 匹配数据证明具有高度的鉴别力。在以前被认为完全匹配的患者(1DPmm=49pts:2DPmm=28pts)中,87%的患者存在错配,在 9/10 组中,22 例患者被重新分类为双错配,16 例为三错配。在 10/10 移植中,双 DPBMm 与较差的 OS 存在明显趋势。如果考虑所有 12 个位点,98%的单 mm 都位于 HLA-DPB1。此外,两个或更多位点的累积 mm 与显著较差的 3 年 OS 相关(34%vs48%,P=0.013:风险比 1.8(95%置信区间 1.14-3.06;P=0.017),尽管这种不利影响仅在使用 MA 预处理时才明显,在 MA 预处理中,降低 OS 与慢性 GVHD(61%vs16%,P=0.018)和非复发死亡率(30%vs9%,P=0.039)增加相关。