Burden and Impact of Infectious Complications After Allogeneic Hematopoietic Cell Transplantation in Older Patients:...

Infectious complications remain a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). With the increasing use of allo-HCT in older adults, the burden and clinical impact of infections in this population remain poorly characterized. The objective is to characterize the epidemiology of microbiologically documented infections during the first year after allo-HCT in patients aged ≥65 years and to identify risk factors for infectious complications. This retrospective multicenter study included consecutive patients aged ≥65 years undergoing a first allo-HCT in 13 Spanish centers between 2011 and 2023. Microbiologically documented infections occurring within the first year post-transplant, or until relapse or death, were analyzed. Cumulative incidence (CI), infection density, and multivariable models were used to identify risk factors and assess clinical outcomes. Overall, 568 of 726 allo-HCT recipients (78.2%) experienced ≥ 1 infectious episode, with an overall infection density of 8.77 per 1,000 patient-days. Viral and bacterial infections were most common, affecting 60.6% and 54.8% of patients, respectively. At 1 year, the CI of bacterial infection was 53.6% (density 4.31 per 1,000 patient-days), invasive fungal disease (IFD) 11.7% (density 0.47 per 1,000 patient-days), and CMV infection 44.0%. Infection-related mortality at 1 year was 12.4%, mainly driven by Gram-negative bacterial and Aspergillus infections. The occurrence of any infectious episode was independently associated with inferior overall survival (OS; HR 1.6, 95% CI 1.3-2.1) and higher non-relapse mortality (NRM; HR 3.4, 95% CI 2.3-4.9). Bacterial infections, IFD, and CMV infection were independently associated with inferior OS and increased NRM. Across infection-specific multivariable analyses, poor functional status, haploidentical transplantation, and GvHD emerged as the principal determinants of infectious burden, whereas antibacterial prophylaxis and letermovir were protective. In conclusion, in older allo-HCT recipients, infectious complications affected a large proportion of patients and have a substantial impact on survival. Functional status and donor type independently modulate susceptibility to infection, highlighting the need for refined risk stratification and tailored preventive strategies. Infection density may provide a useful complementary measure to better capture the burden of recurrent infectious events in this population.