Impact of early bacteremia 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 highlighting Candida, Enterococcus, and gram-negative rods (GNRs) as predominant pathogens. However, the broader clinical impact of pathogen-specific bacteremia on post-HCT outcomes in PTCy recipients remains incompletely defined. We aimed to study allo-HCT outcomes in patients who developed bacteremia in 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 logistic and 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 treatment-related mortality (TRM). Adjusted covariates included patient age, gender, disease type, conditioning intensity, graft source, donor type, HCT-CI, and Karnofsky performance score. Results A total of 385 patients who developed bacteremia 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 3.9% received anti-thymocyte globulin. Graft source was peripheral blood stem cells (PBSC) in 54.8%, bone marrow 45.2% and 0.3% received cord blood. 51.2% had a Karnofsky Performance Score of <90 and 53.8% had HCT-comorbidity index score of >3. Among the patients studied, bloodstream infection with certain pathogens within the first 100 days post-transplant significantly influenced multiple clinical outcomes. In univariate analyses, bloodstream infection with Candida (HR 3.10, 95% CI 1.22–7.87, p = 0.017), Enterococcus spp. (HR 1.72, 95% CI 1.21–2.45, p = .003), and non-Enterobacteriaceae gram-negative rods (HR 2.34, 95% CI 1.34–4.08, p = .003) were associated with worse survival outcomes. TRM was significantly elevated in patients with bacteremia due to Candida (HR 3.27, 95% CI 1.43–7.48, p = .005), Enterococcus spp. (HR 1.84, 95% CI 1.15–2.94, p = .011), non-Enterobacteriaceae GNRs (HR 2.40, 95% CI 1.44–4.02, p < .001), and other fungal infections (HR 5.11, 95% CI 1.61–16.19, p = .006). Bacteremia with Enterococcus spp. (HR 1.66, 95% CI 1.12–2.47, p = 0.012) and yeast organisms (HR 9.74, 95% CI 2.37–40.02, p = 0.002) was also associated with increased risk of acute GVHD II-IV. Delayed neutrophil recovery was more frequent with infections due to Enterobacteriaceae (HR 1.27, 95% CI 1.01–1.59, p = 0.040). On multivariable analysis, invasive fungal infections and other fungal infections were associated with an increased risk of mortality (HR 3.10 95% CI 1.22–7.87; p = 0.017 and HR 3.74, 95% CI 1.07–13.07; p = 0.039, respectively). Non-Enterobacteriaceae gram negative rod bacteremia was also independently associated with inferior survival (HR 2.34; 95% CI, 1.34–4.08; p = 0.003). Additionally, Enterococcus bacteremia was significantly associated with an increased risk of developing acute GVHD grade II–IV (HR, 1.50; 95% CI, 1.00–2.26; p = 0.050). No other infections significantly affected outcomes in multivariable analyses. 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 due to Candida, Enterococcus spp., and non-Enterobacteriaceae GNRs were associated with worse survival and increased risk of acute GVHD. These findings highlight the importance of enhanced antimicrobial surveillance and interventions to protect patients against high-risk pathogens.

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