Bacterial Prophylaxis in Patients with Acute Gvhd; Who Is at Risk for Bloodstream Infections?
Authors: Wallis Whitney , Gulbis Alison , Wang Tao , Chen Karen , Kitko Carrie Lynn , MacMillan Margaret L. , Pidala Joseph , Riches Marcie L. , Spellman Stephen R. , Arora Mukta , Alousi Amin M. 
Published: November 2021

Consensus on the need for antibacterial prophylaxis in patients with acute graft-vs.-host disease (AGVHD) has not been established with practices varying across centers. The aim of this study was to determine the risk for bacterial bloodstream infections (BSI) from neutrophil engraftment through day 100 post-hematopoietic cell transplant (HCT) in patients with AGVHD and whether organ involvement and severity impact this risk.

Methods: The cause-specific hazards for developing BSI after-engraftment by day 100 was compared between patients with and without grade II-IV AGVHD by treating AGVHD as a time-dependent variable.

Results: A total of 4064 adult patients who underwent a matched related, matched unrelated, or mismatched unrelated T-cell replete, marrow or blood HCT for AML, ALL, or MDS from 2008-2012 within the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients, 62% of which had lower GI involvement and 70% had skin involvement. In multivariate analysis (MVA), the hazard ratio for BSI was 1.83 (95% CI: 1.53-2.18; p&lt;0.0001) in those with grade II-IV AGVHD vs. those with grade 0/I. Patients with grade III/IV AGVHD had the highest risk for BSI (HR 2.45; 95% CI 1.99-3.0; p &lt;0.0001) with a borderline risk for those with grade II (HR 1.35; 95% CI 1.03-1.77; p=0.0275). Patients with lower GI involvement had higher risk when compared to those with grade II-IV AGVHD without GI involvement (HR 1.54; 95% CI 1.17-2.02; p=0.0019) with risk being incrementally higher with each lower GI stage (1-4). Patients with isolated stage 3 skin AGVHD (n=214) did not have significantly higher risk for BSI (HR 1.25; 95% CI 0.82-1.91; p= 0.3); however, those with isolated stage 4 (n=27) had higher risk (HR 3.30; 95% CI 1.74-6.27; p=0.0003) when compared to those with grade 0/I AGVHD. In MVA, patients who developed a BSI between engraftment and day 100 post-transplant had worse survival (HR 1.64, 95% CI 1.43-1.87; p &lt;0.001) and higher non-relapse mortality (NRM), HR 2.22; 95% CI 1.91-2.59; p &lt;0.001). When evaluating type of infections: Gram negative bacteremia was seen in a higher proportion of patients (7%) with lower GI involvement vs. 4% in those without lower GI involvement and 4% in those with grade 0/1 AGVHD (p &lt;0.01). Staphylococcus aureus bacteremia was seen in a higher proportion of patients with grade 2-4 AGVHD with skin involvement (4%) vs. 2% in those without skin involvement and 1% in those with grade 0/1 AGVHD (p &lt;0.01).

Conclusions: Patients with grade II-IV AGVHD are at higher risk for BSI compared to patients with grade I AGVHD or no AGVHD. Those with lower GI involvement or with stage 4 skin AGVHD are at highest risk. The development of BSI is associated with worse survival and higher NRM. Strategies for the lowering the risk for BSI in high risk patients are needed.

Figure 1 Figure 1.

Disclosures

Gulbis: EUSA Pharma: Other: Advisory board participation. Kitko: Vanderbilt University Medical Center: Current Employment; Co-investigator on two NIH grants as part of the cGVHD consortium: Research Funding; Horizon: Membership on an entity's Board of Directors or advisory committees; PER: Other: PER - CME educational talks about GVHD. MacMillan: Equilium: Other: DSMB member; Incyte: Consultancy; Jazz Pharmaceuticals: Consultancy. Pidala: CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Regeneron: Consultancy; Pharmacyclics: Other: Clinical trial support, Research Funding; Incyte: Consultancy; Takeda: Other: Clinical trail support; Novartis: Other: Clinical trail support; BMS: Other: Clinical trial support, Research Funding; Johnson and Johnson: Other; Jannssen: Other: Clinical trial support; BMS: Other; AbbVie: Other. Riches: Jazz Pharmaceuticals: Other: Payment; BioIntelect: Membership on an entity's Board of Directors or advisory committees; ATARA Biotherapeutics: Other: Payment. Arora: Kadmom: Research Funding; Syndax: Research Funding; Pharmacyclics: Research Funding.