2121. The Impact of Donor CMV Serostatus on Outcomes of CMV Infections in the Era of Letermovir
Authors: Aramburo Oscar Morado , Spallone Amy , Khawaja Fareed , Sassine Joseph , Srinivasan Krithia , Febres-Aldana Anthony J , Shigle Terri Lynn , Rondon Gabriella , Ramdial Jeremy , Shpall Elizabeth , Ariza-Heredia Ella , Chemaly Roy F 
Published: December 2022

Abstract

Background
Cytomegalovirus (CMV) infection is a frequent complication after allogeneic hematopoietic cell transplant (allo-HCT) and may increase the risk of other viral infections through its immunomodulatory effects. Donor CMV serology (seropositive [D+] or seronegative donor [D-]) in CMV-seropositive (R+) or seronegative recipients (R-) may impact outcomes post allo-HCT. We analyzed the significance of donor CMV serostatus in a large cohort of alloHCT recipients.

Methods
This is a single-center, retrospective cohort study of 651 allo-HCT recipients cared for at our institution between March 2016 and December 2018. Data on baseline demographics, transplant characteristics, preventive strategies, CMV infection characteristics, and transplant-related outcomes (development of graft versus host disease (GVHD), all-cause mortality, and non-relapse mortality) were collected. A univariate analysis was performed for outcomes of interest using CMV serostatus D-/R- as a control group.

Results
Out of the 651 allo-HCT recipients, 77 were D-/R-, 43 D+/R-, 290 D+/R+, and 241 D-/R+ (table 1). Most patients underwent HCT for AML (40%), received myeloablative conditioning (51%), and had a matched unrelated donor (MUD) HCT (46%). In 2018, letermovir was used in 27% of the D+/R+, 18% of the D-/R+ allo-HCT recipients (table 1) for a total of 116 (55%) allo-HCT recipients. Compared to the CMV D-/R- group, D+/R+ and D-/R+ groups (table 2) had a greater incidence of clinically signicant CMV infections (CS-CMVi) (3.9% vs. 40% vs. 50.6%; all p&lt; 0.01, respectively), CMV end organ disease (0% vs. 14.8% vs. 19.1%; all p&lt; 0.001, respectively), and refractory/resistant (R/R) CMV infections (0% vs. 5.5% vs. 12.4%; all p&lt; 0.03, respectively) with 48 weeks of allo-HCT. CS-CMVi and R/R CMV was more common in D-/R+ allo-HCT when compared to D+/R+ group (50.6% vs. 40.0%, p&lt; 0.001). D-/R+ allo-HCT had worse non-relapse mortality at day 100 compared to D-/R- (3.9% vs. 10.8%, p=0.07). Table 1:Baseline characteristicsTable 2:Outcome analysis

Conclusion
Allo-HCT recipients with CMV seronegative donor and recipient had less CMV related complications and a trend towards better survival when compared to D-/R+ allo-HCT. CMV D-/R+ HCT recipients had greater CMV related complications when compared to CMV D+/R+ HCT recipients, possibly due to the protective affect of donor seropositivity.

Disclosures
Terri Lynn Shigle, PharmD, BCOP, Takeda: Advisor/Consultant Gabriella Rondon, MD, Omeros: Advisor/Consultant Elizabeth Shpall, MD, Adaptimmune: Advisor/Consultant|Affimed: License agreement|Axio: Advisor/Consultant|Bayer Helathcare Pharmaceuticals: Honoraria|Fibroblasts and FibrioBiologics: Advisor/Consultant|Navan: Advisor/Consultant|NY Blood Center: Advisor/Consultant|Takeda: License agreement Ella Ariza-Heredia, MD, MERCK: Grant/Research Support Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.