Anti-thymocyte globulin-resistant CD4+ memory T cells contribute to haplo-fever after allogeneic hematopoietic stem cell transplantation

作者：Hanjun Huang, Ting Lü, Honglin Duan, Jingtao Huang, Quan Gu, Hui Cheng, Zengkai Pan, Xiaoxia Hu · 发表于：Blood Science · 年份：2026 · DOI：10.1097/bs9.0000000000000280 · 研究领域：Hematopoietic Stem Cell Transplantation、T-cell and B-cell Immunology、Cytomegalovirus and herpesvirus research

Haplo-fever (HF) is a form of non-infectious fever that occurs shortly after haploidentical (HID) hematopoietic stem cell transplantation (HSCT). Its clinical significance, risk factors, and pathophysiology, particularly in the context of anti-thymocyte globulin (ATG)-based prophylaxis for graft-versus-host disease (GvHD), remain largely unknown. Here, we retrospectively analyzed clinical data from 143 consecutive HID HSCT recipients. Patients with HF exhibited a higher incidence of chronic GvHD, a lower risk of measurable residual disease recurrence, and improved event-free survival, particularly among those receiving ATG-based acute GvHD prophylaxis. Identified risk factors for HF included higher infused doses of CD34 + cells, mononucleated cells, CD3 + T cells, and CD4 + memory T cells. At 90 days post-transplant, patients with HF demonstrated elevated absolute numbers of CD4 + memory T cells and activated CD4 + and CD8 + T cells. RNA sequencing of peripheral blood CD3 + T cells at day 2 post-transplant revealed transcriptional signatures of T-cell activation and an abundance of activated CD4 + memory T cells as hallmarks of HF. Using multiple complementary approaches, we demonstrated the impact of HF on transplant outcomes, identified its risk factors, and elucidated the underlying cellular and molecular mechanisms.