The Effect Of Donor and Recipient Statin Treatment On Infections After Allogeneic Hematopoietic Cell Transplantation
Authors: Seo Sachiko , Boeckh Michael , Storer Barry E. , Schubert Mark M , Rotta Marcello , Sandmaier Brenda M. , Mielcarek Marco 
Published: October 2019

Background
Recent studies have reported that statin use is associated with improved outcomes in immunocompetent patients with bacterial sepsis and respiratory virus disease. We have reported previously that statin use in donors or recipients was associated with reduced risks of severe acute graft-versus-host disease (GVHD) or chronic GVHD, respectively, after allogeneic hematopoietic cell transplantation (HCT). In the present study, we analyzed the influence of donor and recipient statin use on the incidence of infections and infection-outcomes after allogeneic HCT.

Patients and Methods
A previously reported cohort of HCT recipients (BBMT 16:1463-6, 2010) was used for the analyses. The cohort included 1206 allogeneic HCT recipients (no statin treatment: n=1130; statin treatment: n=76) transplanted between 2001 and 2008 at the Fred Hutchinson Cancer Research Center. Recipients were considered “statin-treated” when a statin was used to treat hyperlipidemia before and after HCT-conditioning. In addition, for all 567 sibling donors in the same cohort, the statin treatment status at the time of stem cell donation was assessed by review of medical records (no statin treatment: n=480, statin treatment: n=87; Blood 115:1288-95, 2010). The associations between statin use and risks of incident infections or infection-related mortality were evaluated using Cox proportional hazards models.

Results
Among 1206 HCT recipients, the following proportions experienced first infectious events within 100 days after HCT: bacteremia, 23% (n=275); CMV reactivation, 23% (n=277); respiratory viral infection with upper and/or lower respiratory tract involvement, 8.0% (n=97), and with only lower respiratory tract involvement (LRI), 1.8% (n=22). Within 1 year after HCT, 13% (n=153) developed invasive fungal infections and 3.7% (n=45) developed CMV disease. The overall incidences of bacteremia, invasive fungal infection, CMV reactivation, CMV disease, and LRI were not impacted by recipient or donor statin use. Recipient statin-use, however, was associated with a significantly increased cumulative incidence of gram-negative bacteremia (adjusted HR 2.15 [95% CI, 1.1-4.1], p=0.02), an association not observed with donor statin use. The risk of 30-day mortality attributable to gram-negative bacteremia was not significantly affected by recipient or donor statin use. Finally, the risk of respiratory viral infections was increased in recipients transplanted from statin-treated donors compared with those transplanted from donors not treated with a statin (adjusted HR 2.7 [95% CI, 1.3-5.6], p=0.01). There were no progressions to LRI among recipients transplanted from statin-treated donors (0% vs. 15%, p=0.15).

Conclusions
Recipient or donor statin use did not alter incidence of most infections after allogeneic HCT. However, while recipient statin use was associated with an increased risk of gram-negative bacteremia, donor statin use was associated with an increased risk of recipient respiratory viral infections without affecting mortality or progression to LRI. The mechanisms underlying these associations remain unknown. Validation of the findings in other large cohorts and, ultimately, randomized trials are needed.

Disclosures:
Boeckh: Merck: Consultancy, Research Funding.