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亲缘 HLA 单倍型不合移植中谁是最佳供者?

Who is the best donor for a related HLA haplotype-mismatched transplant?

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; and.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; and Peking-Tsinghua Center for Life Sciences, Beijing, China.

出版信息

Blood. 2014 Aug 7;124(6):843-50. doi: 10.1182/blood-2014-03-563130. Epub 2014 Jun 10.

Abstract

The best donor for a related donor for a human leukocyte antigen (HLA) haplotype-mismatched transplant for hematological neoplasms is controversial. We studied outcomes in 1210 consecutive transplant recipients treated on a uniform protocol. Younger donors and male donors were associated with less nonrelapse mortality (NRM; hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.01-0.39; P = .008 and HR = 0.65; 95% CI = 0.49-0.85; P = .002) and better survival (HR = 0.73; 95% CI = 0.54-0.97; P = .033 and HR = 0.73; 95% CI = 0.59-0.91; P = .005). Father donors were associated with less NRM (HR = 0.65; 95% CI = 0.45-0.95; P = .02), acute graft-versus-host disease (GVHD) (HR = 0.69; 95% CI = 0.55-0.86; P = .001), and better survival (HR = 0.66; 95% CI = 0.50-0.87; P = .003) compared with mother donors. Children donors were associated with less acute GVHD than sibling donors (HR = 0.57; 95% CI = 0.31-0.91; P = .01). Older sister donors were inferior to father donors with regard to NRM (HR = 1.87; 95% CI = 1.10-3.20; P = .02) and survival (HR = 1.59; 95% CI = 1.05-2.40; P = .03). Noninherited maternal antigen-mismatched sibling donors were associated with the lowest incidence of acute GVHD compared with parental donors and noninherited paternal antigen-mismatched sibling donors. Specific HLA disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA haplotype-mismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms.

摘要

对于 HLA 单倍型不匹配的血液病患者,寻找最佳的亲缘供者一直存在争议。我们通过研究 1210 例接受同种异体移植患者的治疗结果,制定了一套统一的治疗方案。结果显示,年轻的供者和男性供者的非复发死亡率(NRM)较低(风险比 [HR] = 0.30;95%置信区间 [CI] = 0.01-0.39;P =.008 和 HR = 0.65;95% CI = 0.49-0.85;P =.002),且生存状况更好(HR = 0.73;95% CI = 0.54-0.97;P =.033 和 HR = 0.73;95% CI = 0.59-0.91;P =.005)。与母亲供者相比,父亲供者的 NRM 较低(HR = 0.65;95% CI = 0.45-0.95;P =.02),急性移植物抗宿主病(GVHD)(HR = 0.69;95% CI = 0.55-0.86;P =.001)的发生率较低,生存状况更好(HR = 0.66;95% CI = 0.50-0.87;P =.003)。与同胞供者相比,儿童供者的急性 GVHD 发生率较低(HR = 0.57;95% CI = 0.31-0.91;P =.01)。与父亲供者相比,年龄较大的姐姐供者的 NRM 更高(HR = 1.87;95% CI = 1.10-3.20;P =.02),生存状况更差(HR = 1.59;95% CI = 1.05-2.40;P =.03)。与父母供者和非血缘 HLA 单倍型不匹配的同胞供者相比,非血缘、母系 HLA 抗原不匹配的同胞供者的急性 GVHD 发生率最低。特定的 HLA 差异与移植结果无显著相关性。我们的数据表明,在血液病患者中,与 HLA 单倍型不匹配的亲缘供者相比,哪些 HLA 单倍型不匹配的亲缘供者与最佳的移植结果相关。

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