Infectious Disease Screening in Hematopoietic Cell Donors: Risk Assessment, Regulation, and Selective Donor Utilization

Donor-derived infections in hematopoietic cell transplantation (HCT) are uncommon but potentially severe complications that remain largely preventable through rigorous donor screening and risk mitigation strategies. Although reported incidence appears low, donor-derived infections are associated with substantial morbidity and mortality when transmission occurs in profoundly immunocompromised recipients. In the United States, donor eligibility is governed by Food and Drug Administration requirements for screening and testing for relevant communicable disease agents and diseases. European and international frameworks similarly require comprehensive donor evaluation and testing for major transmissible infections, with additional testing guided by epidemiologic and exposure risk. A key challenge across jurisdictions is distinguishing regulatory donor eligibility from clinical donor suitability and determining when individualized donor-recipient risk assessment is appropriate. Advances in nucleic acid testing have markedly shortened diagnostic window periods for blood-borne pathogens. Concurrently, highly effective antiviral therapies, particularly for hepatitis B and hepatitis C, have transformed select historically prohibitive infections into increasingly manageable risks. These developments have supported selective clinical consideration of donors who remain ineligible under traditional regulatory criteria when an applicable regulatory pathway permits use. This review examines pathogen-specific transmission risk, contemporary screening strategies, and evolving approaches to donor eligibility in HCT. Future donor screening frameworks will likely evolve toward adaptive, pathogen-specific models that integrate molecular diagnostics, recipient mitigation strategies, and real-world transplant outcomes to optimize both safety and donor access.