Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience

Anthony Febres-Aldana; Fareed Khawaja; Oscar Morado-Aramburo; Terri Lynn Shigle; Gabriela Rondon; Joseph Sassine; Amy Spallone; Krithika Srinivasan; Jeremy Ramdial; Amin Alousi; Richard Champlin; George Chen; May Daher; Katayoun Rezvani; Ella J Ariza-Heredia; Elizabeth J Shpall; Roy F Chemaly

doi:10.1016/j.cmi.2024.03.001

Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience

Clin Microbiol Infect. 2024 Mar 8:S1198-743X(24)00113-7. doi: 10.1016/j.cmi.2024.03.001. Online ahead of print.

Authors

Anthony Febres-Aldana¹, Fareed Khawaja², Oscar Morado-Aramburo², Terri Lynn Shigle³, Gabriela Rondon⁴, Joseph Sassine⁵, Amy Spallone², Krithika Srinivasan², Jeremy Ramdial⁴, Amin Alousi⁴, Richard Champlin⁴, George Chen⁴, May Daher⁴, Katayoun Rezvani⁴, Ella J Ariza-Heredia², Elizabeth J Shpall⁴, Roy F Chemaly⁶

Affiliations

¹ Department of Infectious Diseases, Infection Control & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Medicine, Division of Infectious Disease, Moffitt Cancer Center, Tampa, FL, USA.
² Department of Infectious Diseases, Infection Control & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Division of Pharmacy, The University of Texas MD Anderson Cancer Centre, Houston, TX, USA.
⁴ Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Infectious Diseases Section, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁶ Department of Infectious Diseases, Infection Control & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: rfchemaly@mdanderson.org.

PMID: 38460821
DOI: 10.1016/j.cmi.2024.03.001

Abstract

Objectives: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes.

Methods: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D^-/R^-, R⁺/LTV^-, and R⁺/LTV⁺. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D^-/R^- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions.

Results: The analysis included 1071 consecutive allo-HCT recipients: 131 D^-/R^-, 557 R+/LTV^-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D^-/R^- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV^- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV^-, R+/LTV+, and D^-/R^- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV^- compared with D^-/R^- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D^-/R^-.

Discussion: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.

Keywords: Cytomegalovirus; Haematopoietic cell transplantation; Immunocompromised; Letermovir; Prophylaxis.