U.O. Ematologia, Ospedale Policlinico San Martino, Genova, Italy.
Ematologia, Università Federico II, Napoli, Italy.
Biol Blood Marrow Transplant. 2018 Jan;24(1):119-126. doi: 10.1016/j.bbmt.2017.10.002. Epub 2017 Oct 9.
We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.
我们研究了 HLA 错配对 318 例连续接受未经处理的单倍体相合骨髓移植,随后接受移植后环磷酰胺(PTCy)治疗的患者结局的影响。我们检测了 HLA 错配抗原的数量对总生存率(OS)和非复发死亡率(NRM)的影响,而移植物抗宿主病(GVHD 和复发的方向的 HLA 错配则用于预测。最后,我们研究了宿主抗移植物(HVG)方向的 HLA 错配数量是否与移植物排斥相关。231 对供体-受者(72%)在-HLA 基因座存在 4/8 错配。HLA 错配不能预测 2 年 OS(风险比,.83;P = .58)和 NRM(亚风险比,1.08;P = .93)。急性 GVHD 的累积发生率(P = .13)、1 年慢性 GVHD(P = .84)和复发率(P = .26)与单向 GVH 错配无关。同样,HVG 方向的 HLA 错配数量与移植物排斥之间也没有观察到相关性。在多变量分析中,移植时的疾病进展是生存、NRM、复发和移植物排斥的最强预测因素。总之,在使用骨髓作为干细胞来源和 PTCy 预防 GVHD 时,HLA 错配程度不应作为选择家族单倍体相合供者的标准。