单倍体造血干细胞移植模式下供者HLA-Bw4对移植后NK细胞重建及移植相关死亡风险的影响

The impact of donor human leukocyte antigen-Bw4 allele on natural killer cell reconstitution and transplant-related mortality in haploidentical transplantation

目的探讨在接受来自母体或旁系供者的非去T细胞单倍体造血干细胞移植时, 供者HLA-Bw4表达对NK细胞重建和移植预后的影响。方法本研究前瞻性入组了32例接受来自母体或旁系的供者非去T细胞单倍体移植患者(队列1), 评估供者HLA-Bw4表达对NK细胞重建的影响;同时回顾性研究了278例接受来自母体或旁系的供者非去T细胞单倍体移植患者(队列2), 分析供者HLA-Bw4对HSCT预后的影响。同时还分别比较了在接受移植后环磷酰胺(PT-Cy)和不接受PT-Cy的情况下, 供者HLA-Bw4表达对HSCT预后影响的差异。结果编码HLA-Bw4的供者促进了NK细胞的重建和功能恢复, PT-Cy体内应用并未影响供者HLA-Bw4促进NK细胞重建。编码HLA-Bw4的供者与移植相关死亡率(Transplantation-related mortality, TRM), 尤其是感染相关的TRM(infection-related TRM)降低相关, PT-Cy体内应用并未影响供者HLA-Bw4降低TRM。结论在进行来自母体或旁系供者的非体外去T细胞单倍体移植时, 编码HLA-Bw4的供者有助于快速NK细胞重建和功能恢复, 并且与较低的TRM(尤其是感染相关TRM)显著相关。这些结果表明, 供者HLA-Bw4的表达对于单倍体移植患者的临床结果具有重要意义。因此, 在供受者选择和移植策略中, 考虑供者HLA-Bw4可能具有临床意义。

Objective To investigate the impact of donor human leukocyte antigen(HLA)-Bw4 expression on natural killer(NK)cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation(HSCT)from maternal or related donors without ex vivo T-cell depletion.Methods This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors(cohort 1)to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution.Furthermore,a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors(cohort 2)to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes.Thus,a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide(PT-Cy)conditioning.Results Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery,which remained unaffected by PT-Cy.Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality(TRM),particularly mortality related to infections.The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion,the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM,especially infection-related mortality.These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT.Hence,the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.