Impact of infectious complications on outcomes after allogeneic hematopoietic stem cell transplantation in elderly patients: A geth-TC study

Abstract

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) is increasingly performed in elderly patients, a population affected by immunosenescence, which may increase susceptibility to infections and negatively impact alloHSCT outcomes. Despite this, data on the spectrum and timing of infectious complications in older recipients remain limited. This study describes the etiology, frequency, and temporal distribution of infections in a large cohort of elderly alloHSCT recipients. Methodology We conducted a retrospective review of all patients aged ≥65 who underwent a first alloHSCT between 2011 and 2023 across 12 Spanish centers. We collected all microbiological isolates (bacteria, fungi, viruses, and parasites) obtained during the first year post-transplant or until death or relapse, whichever occurred first. Results A total of 625 patients were included, 63.4% were male and the median age was 68 years (range 65-84). The most common diagnoses were acute myeloblastic leukemia (44.3%) and myelodysplastic and/or myeloproliferative neoplasms (33.8%). ECOG 0 was present in 52.2% of patients, HCT-CI <3 in 58.1%, and high/very high DRI in 26.5%. Peripheral blood was the stem cell source in 87.0% of cases. Donors included HLA-identical siblings (28.6%), haploidentical relatives (34.2%), HLA-matched unrelated (28.0%) and HLA-mismatched unrelated (9.1%) donors. Myeloablative conditioning was used in 24.2% of patients, and 54.9% received post-transplant cyclophosphamide-based GvHD prophylaxis. A total of 493 patients (78.9%) experienced at least one infectious episode (median 2, range 1-22). Bacterial infections were the most common, with 727 bacterial isolates in 351 patients (56.2%), with 14.4% experiencing ≥3 episodes. Among these, Gram-negative bacteria predominated (439 isolates, 60.4%), primarily Escherichia coli (174, 39.6%), Klebsiella pneumoniae (47, 10.7%), and Pseudomonas aeruginosa (42, 9.6%). Gram-positive bacteria accounted for 285 isolates (39.2%), led by Staphylococcus epidermidis (97, 34.0%) and Enterococcus spp. (81, 28.4%). The median time to first bacterial infection was 16 days, with bloodstream and urinary tract infections being the most frequent. Notably, multidrug resistance was present in 21.0% of bacterial isolates. A total of 154 fungal infections were identified in 114 patients (18.2%), with 98 (63.6%) yeast infections, mostly caused by Candida spp., affecting 72 patients (11.5%) and a median onset of 29 days. Invasive mold infections, mainly due to Aspergillus spp., were diagnosed in 56 patients (9.0%), with a median onset at 49 days and recurrence occurring in 9.1% of these cases. Viral infections were also common: cytomegalovirus (CMV) infection was detected in 273 patients (43.7%), with 77 (12.3%) experiencing recurrence and 21 (3.4%) developing CMV disease, predominantly affecting the gastrointestinal tract, at a median onset of 41 days. Ebstein-Barr virus infection was observed in 21 patients (3.4%), with only 2 patients (0.3%) progressing to post-transplant lymphoproliferative disorder. A total of 164 respiratory viruses were identified in 128 patients (20.5%), chiefly rhinovirus (47, 28.7%), SARS-CoV-2 (33, 20.1%), and influenza virus (27, 16.5%), with a median onset of 118 days. Other viral infections including herpes simplex virus, human herpesvirus 6, Varicella-Zoster virus, and disseminated adenovirus were less common (<3%). Additionally, BK virus-associated cystitis was diagnosed in 90 patients (14.4%). Parasitic infections were rare, occurring in only 10 patients (1.6%). These involved Toxoplasma gondii, Cryptosporidium spp., and Giardia lamblia, with a median onset of 111 days post-transplant. The median follow-up was 5 years. At the last follow-up, 277 patients (44.3%) remained alive. The 1-year overall survival and disease-free survival were 62.4% and 55.6%, respectively. Non-relapse mortality and infection-related mortality (IRM) at 1-year were 23.9% and 12.3%, respectively. The main pathogens responsible for IRM were Aspergillus spp. and Escherichia coli. Conclusions Infections are a major cause of morbidity and mortality in elderly alloHSCT patients, driven by early bacterial/fungal and late viral infections. Further studies comparing these findings with younger cohorts are needed to optimize supportive care and clarify age-specific risk factors.