Incidence, etiology, risk factors, and outcomes of pre-engraftment bloodstream infections after first and second allogeneic hematopoietic cell transplantation

Abstract

Introduction: With an increasing number of allogeneic hematopoietic cell transplantations (allo-HCT) bloodstream infections (BSI) are still among the most common and serious complications. This study aimed to analyze the incidence, etiology, risk factors, and outcomes of pre-engraftment BSI after the first and the second allo-HCT.

Materials and methods: This is a retrospective study of 284 patients who underwent the first allo-HCT and 37 patients after the second allo-HCT at the National Research Center for Hematology in Moscow, Russia, from January 2018 till September 2021.

Results: Cumulative incidence of pre-engraftment BSI was 29.9% after the first allo-HCT and 35.1% after the second (p = .805). The median time to the first BSI was 9 days (range 0-61 days) after the first and 16 days (range 1-28 days) after the second allo-HCT (p = .014). A total of 113 pathogens were isolated during 94 BSI episodes after the first allo-HCT (gram-negative bacteria 52.2%; gram-positive bacteria 47.7%). Fourteen pathogens were isolated during 14 BSI episodes after the second allo-HCT (gram-negative bacteria 50.0%; gram-positive bacteria 50.0%). The only significant difference was found in the rate of carbapenem-resistant gram-negative bacteria, which was higher after the second allo-HCT compared to the first (57.1% vs. 13.6%; p = .048). Mismatched unrelated donor (hazards ratio [HR] 3.01; 95% confidence interval [CI]: 1.62-5.60; p < .0001) and haploidentical donor transplantations (HR 1.84; 95% CI: 1.02-3.33; p = .042) were the only independent risk factors associated with the higher risk of pre-engraftment BSI. Overall 30-day survival after all BSI episodes was 94.4%. Survival was lower after BSI during the second allo-HCT compared to the first (71.4% vs. 97.9%; p < .0001), particularly after BSI was caused by carbapenem-resistant gram-negative bacteria (25.0% vs. 100.0%; p = .0023). The non-relapse mortality rate at day +60 was 4.0%, and the risk was highly associated with primary graft failure (HR 9.62; 95% CI: 1.33-71.43), second allo-HCT (HR 6.80; 95% CI: 1.36-34.48), and pre-engraftment BSI caused by carbapenem-resistant gram-negative bacteria (HR 32.11; 95% CI: 4.91-210.15).

Conclusions: Pre-engraftment BSI is still a common complication after allo-HCT, particularly after mismatched unrelated and haploidentical donor transplantations. BSI incidence was slightly higher after the second allo-HCT with a significantly higher rate of carbapenem-resistant BSI. Although pre-engraftment BSI would generally follow a benign clinical course, survival was dramatically lower during the second allo-HCT, especially after carbapenem-resistant BSI.

Keywords: BSI; allo-HCT; bloodstream infections; pre-engraftment; risk factors.