Bone marrow accumulation of perfluoroalkyl substances (PFASs) predicts post-transplant relapse in acute myeloid leukemia patients and associated with T-cell dysregulation.

Perfluoroalkyl substances (PFAS) are immunotoxic environmental pollutants, but their impact on hematopoietic stem cell transplantation (HSCT) remains unknown. We hypothesized that bone marrow (BM) accumulation of PFAS predicts acute myeloid leukemia (AML) relapse post-HSCT by dysregulating T-cell immunity. In a prospective cohort of 21 AML patients in morphological remission about one-month post-HSCT, we quantified 32 PFAS congeners in BM plasma and performed immunophenotyping of T-cell subsets. Patients who subsequently relapsed showed significantly elevated BM levels of PFOA, PFOS, 9Cl-PF3ONS, and PFUnDA compared to those sustaining remission, with all four congeners demonstrating high predictive accuracy for relapse in ROC analysis. Furthermore, in relapsed patients, PFOA, PFOS, 9Cl-PF3ONS, and 11Cl-PF3OUdS were specifically associated with a coordinated suppression of effector memory (TEM) and expansion of central memory (TCM) T-cells, suggesting that these PFASs might impair graft-versus-leukemia immunity by potentially mediating T-cell differentiation toward regulatory phenotypes, linking to AML relapse. This study provides the first clinical evidence linking BM PFAS accumulation to post-transplant relapse, potentially through T-cell immunotoxicity that compromises graft-versus-leukemia immunity. These findings also necessitate future studies to establish causal mechanisms through in vivo models and to develop clinical strategies for PFAS mitigation to improve curative outcomes in HSCT.