A new analysis of data from a phase 3 clinical trial delineates how two immune-suppression treatments shape T cell immunity and lower or raise the risk of complications in recipients of stem cell transplants. The data from 324 patients suggest that clinicians must carefully weigh the application of cyclophosphamide and tacrolimus, as each drug had different long-term effects on the recovering T cell compartment and on the subsequent risk of infections and graft-versus-host disease (GVHD). “[These findings] begin to unravel the essential paradox of allogenic [stem cell transplant]: how to balance the hazard of robust donor T cell number, diversity, and function (GVHD) against the fundamentally beneficial role of T cells in immune health,” Susan DeWolf and colleagues write. Recipients of stem cell transplants must take drugs to suppress the immune system and prevent GVHD, which occurs when the transplanted immune cells attack their new host’s body. Clinicians then confront a tricky dilemma: they must keep T cells in check as the patient recovers to prevent GVHD, but they must also support the immune system’s recovery to ward off infections. DeWolf et al. examined the recuperation of the T cell arm of the immune system in recipients of stem cell transplants involved in a phase 3 clinical trial, who took either cyclophosphamide or a combination of tacrolimus and methotrexate after transplant. They sequenced more than 2,300 longitudinal samples and a massive collection of more than 180 million cells. Cyclophosphamide depleted all branches of T cells and delayed the cells’ recovery from a small starting pool, creating a bottleneck in T cell diversity that lasted for two years after transplant. This correlated with better protection against GVHD compared with tacrolimus, but also depleted anti-pathogen T cells and may have rendered the patients more vulnerable to severe infections.
Science Translational Medicine
Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant
21-Oct-2026