Lymphocyte subset reconstitution and clinical outcomes following haploidentical hematopoietic stem cell transplantation

作者：Peiyao Jiang, Xiao Zhou, Yu Cai, Jun Yang, Kun Zhou, Yin Tong, Chongmei Huang, Baoxia Dong, Huiying Qiu, Xiaowei Xu, Jiahua Niu, Chang Shen, Xinxin Xia, Ying Zhang, Xianmin Song, Liping Wan · 发表于：British Journal of Cancer · 年份：2026 · DOI：10.1038/s41416-026-03345-w · 研究领域：Hematopoietic Stem Cell Transplantation、Cytomegalovirus and herpesvirus research、Acute Myeloid Leukemia Research

BACKGROUND: Immune reconstitution is critical for outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its prognostic role in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) remains unclear. METHODS: We retrospectively analysed 577 patients who underwent T-cell replete haplo-PBSCT between 2016 and 2024. Longitudinal reconstitution of CD4⁺, CD8⁺ T cells and their subsets, CD3⁺CD69⁺, CD3⁺HLA-DR⁺ T cells, NK cells and B cells was assessed from 1 to 12 months post-transplant. Cox regression and causal mediation analyses were performed to identify prognostic associations and mechanisms. RESULTS: Early and robust regulatory T cell (Treg) reconstitution significantly reduced transplant-related mortality (TRM) and improved overall survival. Naïve CD8⁺ T cell recovery correlated with reduced TRM and relapse. Higher late CD3⁺CD69⁺ T cells were linked to decreased relapse risk. Sustained B cell reconstitution reduced TRM and was associated with a lower incidence of moderate-to-severe chronic graft-versus-host disease. Early Treg reconstitution was associated with lower cytomegalovirus (CMV) reactivation. Mediation analysis revealed that Treg recovery reduced TRM partially through suppression of CMV reactivation (ACME = -0.22, p = 0.032). CONCLUSION: Distinct lymphocyte subset reconstitution profiles predict transplant outcomes in haplo-PBSCT. Early Treg recovery, partly by limiting CMV reactivation, may serve as a target for immune-g...