PI-01. Risk factors for bloodstream infections after first allogeneic hematopoietic stem cell transplantation

Summary

Bloodstream infections (BSI) are a major cause of morbidity and mortality among allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. The purpose of this study was to analyze BSI incidence, risk factors and the outcomes after first allo-HCT.

Materials and methods

This retrospective study included 242 patients (50.4% males and 49.6% females) who underwent first allo-HCT in the National Research Center for Hematology during from January 2018 to April 2021. The median age was 35 years (range 17-65 years). Allo-HSCTs were performed from matched related donor (MRD) in 68 (28.1%), matched unrelated donor (MUD) in 51 (21.1%), mismatched unrelated donor (MMUD) in 41 (16.9%), and haploidentical donor in 82 (33.9%) cases. A total of 98 (40.5%) patients without extended spectrum beta-lactamase (ESBL) producing bacteria obtained from rectal swabs received fluoroquinolone-based prophylaxis. Primary and secondary graft failure was detected in 27 (11.2%), and grade II-IV acute GvHD – in 58 (24.0%) patients, accordingly.

Results

Overall, a total of 113 BSI episodes were registered in 95 (39.2%) patients, with one pathogen in 79 cases (83.2%), and 2 or more in 16 (16.8%) patients. The cumulative incidence of pre-engraftment and post-engraftment BSI were 31.0% and 11.0%, accordingly. The median time from allo-HSCT till pre-engraftment and post-engraftment BSI was 8 (range 2-33) days and 64 (range 0-142) days, accordingly. One pathogen was isolated in 94 (82.7%) episodes, two or more – in 19 (17.3%) episodes. A total of 134 different pathogens were isolated: 81 (60.4%) of them were gram-negative, and 53 (39.6%) were gram-positive bacteria. Bloodstream isolates were represented by Escherichia coli (25.3%; n=34), Klebsiella spp (17.9%; n=24), coagulase negative staphylococci (11.2%; n=15), Staphylococcus aureus (9.7%; n=13), Enterobacter spp (9.7%; n=13), streptococci viridans (8.9%; n=12), Pseudomonas aeruginosa (5.9%; n=8), Enterococcus spp (6.7%; n=9), including 6 cases of E.faecium BSI, and other (4.5%; n=6). Among Enterobacter 26.7% (n=19) were ESBL, and 14.0% (n=10) were carbapenemase-producing. In univariate analysis the pre-engraftment BSI risk correlated significantly with donor type, primary graft failure and neutropenia duration of ≥22 days. For post-engraftment BSI, the most significant risk factors were secondary graft failure and poor graft function, donor type, acute GvHD grade II-IV, and acute gut GvHD (Table 1). In multivariate model the pre-engraftment BSI risk was significantly higher in MMUD compared to MRD transplants (HR=2.19; 95% CI:1.08-4.43; p=0.03), wherein post-engraftment BSI cases the most important risk factors were secondary graft failure (HR=30.33 95% CI:8.74-105.20; р<0.0001), poor graft function (HR=18.54 95% CI:4.55-75.62; р<0.0001), and acute gut GvHD (HR=5.62 95% CI: 1.22-25.96; p=0.027). The overall 30-day survival after BSI was 89.9%. It was lower after poly-microbial (76.2%) compared to gram-positive (94.9%) and gram-negative (92.5%) BSI episodes (р=0.06).

Conclusions

Gram-negative bacterial BSI after allo-HCT prevailed in this study. The most significant factors of pre-engraftment BSI were MMUD transplantations, whereas secondary graft failure, secondary poor graft function and acute gut GvHD were associated with higher risk of post-engraftment BSI. Overall 30-day survival was lower after polymicrobial BSI episodes.

Keywords

Hematopoietic stem cell transplantation, bloodstream infections, risk factors.