Impact of Early Bloodstream Infections on Clinical Outcomes Following Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GVHD Prophylaxis.

Abstract

Background: Bloodstream infections (BSIs) remain a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT), particularly during the post-transplant neutropenia and immune reconstitution phase. Notably, studies have identified high rates of BSI in the early post-transplant period with PTCy regimens, including single-center cohorts that have highlighted Candida, Enterococcus, and gram-negative rods (GNRs) as predominant pathogens. However, the broader clinical impact of pathogen-specific BSI on post-HCT outcomes in PTCy recipients remains incompletely defined. We aimed to study allo-HCT outcomes in patients who developed BSI in the first 100 days.

Methods: We performed a retrospective, registry-based cohort analysis using dataset P-5242 from the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult patients who underwent allo-HCT with PTCy-based GVHD prophylaxis between 2009 and 2016 were included. Microbiologically confirmed BSIs within the first 100 days post-HCT were categorized by pathogen. Multivariable Cox proportional hazards models were used to evaluate associations between specific pathogens and acute GVHD (grade II-IV), chronic GVHD, time to neutrophil engraftment (ANC ≥ 500), overall survival (OS), and Non-relapse mortality (NRM). Adjusted covariates included patient age, gender, disease type, conditioning intensity, graft source, donor type, Hematopoietic Cell Transplantation-Comorbidity Index, and Karnofsky performance score.

Results: A total of 385 patients who developed BSI within the first 100 days post-transplant were included. The mean age was 50.0 years (SD 18.6), and 60.5% were male. 49.1% had acute myeloid leukemia (AML), 15.8% had acute lymphoblastic leukemia (ALL), 26.5% had myelodysplastic syndrome (MDS), and 8.6% had non-malignant diseases. Total body irradiation (TBI) was used in 56.4% patients, and only 5.7% received anti-thymocyte globulin. Graft sources were peripheral blood stem cells (PBSC) in 54.8%, bone marrow in 45.2%, and cord blood in 0.3%. 51.2% had a Karnofsky Performance Score of <90, and 53.8% had an HCT-comorbidity index score>3. In multivariable analysis, Candida infections and Enterococcus were associated with inferior survival (HR 3.369, 95% CI, p < 0.001, and HR 1.497, 95% CI, p = 0.049, respectively). Non-Enterobacteriaceae gram-negative rod BSI was also independently associated with inferior non-relapse mortality (HR 2.198; 95% CI, p = 0.003).

Conclusions: This analysis demonstrates that early bloodstream infections significantly alter clinical outcomes in allogeneic hematopoietic stem cell transplant recipients receiving PTCy-based GVHD prophylaxis. Infections caused by Candida, Enterococcus species, and non-Enterobacteriaceae GNRs were associated with poorer survival. These findings highlight the importance of enhanced antimicrobial surveillance and interventions to protect patients against high-risk pathogens.