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供者特异性抗人白细胞抗原(HLA)抗体针对 HLA-DP/-DQ 对脐血移植中植入的不良影响。

Adverse effect of donor-specific anti-human leukocyte antigen (HLA) antibodies directed at HLA-DP/-DQ on engraftment in cord blood transplantation.

机构信息

Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Center for Research and Application of Cellular Therapy, Kyoto University Hospital, Kyoto, Japan.

Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Center for Research and Application of Cellular Therapy, Kyoto University Hospital, Kyoto, Japan.

出版信息

Cytotherapy. 2023 Apr;25(4):407-414. doi: 10.1016/j.jcyt.2022.10.005. Epub 2022 Nov 2.

Abstract

BACKGROUND AIMS

While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in the recipient before transplantation are associated with graft failure in cord-blood transplantation (CBT), effects of DSAs other than against HLA-A, -B or -DRB1 on transplantation outcomes remained poorly understood.

METHODS

We retrospectively analyzed 567 single-unit CBT recipients to evaluate impact of DSAs against HLA-DP and -DQ on CBT outcomes.

RESULTS

Among 143 recipients (25.2%) who had anti-HLA antibodies, nine harbored DSAs against HLA-DP or -DQ. DSAs against HLA-DP or -DQ were associated with a significantly lower neutrophil engraftment rate (55.6% versus 91.8%, P = 0.032) and with a marginally lower platelet engraftment rate (46.7% versus 75.3%, P = 0.128) at day 100 after transplantation, compared with patients without anti-HLA antibodies. Time to neutrophil and platelet engraftment in patients with DSAs for HLA-DP or -DQ was significantly longer than that in patients without anti-HLA antibodies (median, 25 versus 21 days, P = 0.002 in neutrophil; median 61 versus 46 days, P = 0.014 in platelet). Cumulative incidence of bacterial infection at day 100 was significantly greater (88.9% versus 57.1%, P = 0.024), and re-transplant-free survival was marginally lower (55.6% versus 76.8%, P = 0.132) in patients with DSAs against HLA-DP or -DQ, compared with those without anti-HLA antibodies. These findings suggest that DSAs against HLA-DP or -DQ lead to unfavorable engraftment, which may increase risk of bacterial infection, and reduce survival soon after CBT.

CONCLUSIONS

Our results suggest the importance of evaluating DSAs against HLA-DP and -DQ in recipients before selecting CB units.

摘要

背景目的

虽然移植前受者体内针对人白细胞抗原(HLA)的供体特异性抗体(DSA)与脐血移植(CBT)中的移植物衰竭有关,但除 HLA-A、-B 或 -DRB1 以外的 DSA 对移植结局的影响仍知之甚少。

方法

我们回顾性分析了 567 例单份 CBT 受者,以评估针对 HLA-DP 和 -DQ 的 DSA 对 CBT 结局的影响。

结果

在 143 例(25.2%)有抗 HLA 抗体的受者中,有 9 例携带针对 HLA-DP 或 -DQ 的 DSA。与无抗 HLA 抗体的受者相比,针对 HLA-DP 或 -DQ 的 DSA 与显著较低的中性粒细胞植入率(55.6%比 91.8%,P=0.032)和边缘较低的血小板植入率(46.7%比 75.3%,P=0.128)相关,在移植后 100 天。针对 HLA-DP 或 -DQ 的 DSA 患者的中性粒细胞和血小板植入时间明显长于无抗 HLA 抗体的患者(中位数,25 天比 21 天,P=0.002;中位数,61 天比 46 天,P=0.014)。第 100 天的细菌感染累积发生率显著较高(88.9%比 57.1%,P=0.024),针对 HLA-DP 或 -DQ 的 DSA 患者的无复发生存率略低(55.6%比 76.8%,P=0.132),与无抗 HLA 抗体的患者相比。这些发现表明,针对 HLA-DP 或 -DQ 的 DSA 导致植入不良,这可能增加细菌感染的风险,并在 CBT 后不久降低生存率。

结论

我们的结果表明,在选择 CB 单位之前,评估受者针对 HLA-DP 和 -DQ 的 DSA 非常重要。

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