Transplantation and cellular therapy · 2026
Impact of Early Bloodstream Infections on Clinical Outcomes Following Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GVHD Prophylaxis.
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Shahzad Moazzam, Amin Muhammad Kashif, Munir Amna Bint I, Patan Shajadi, Rukh Shah, Akbari Amir Reza, Khaliq Aroog, Yaseen Laiba, Humayun Muhammad Abdullah, Zaheer Amna, Kennedy Vanessa, Snow Anson E, Hamadani Mehdi, McGuirk Joseph, Mushtaq Muhammad Umair
Аннотация
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.
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.