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. 2024 Jun;30(6):803-809.
doi: 10.1016/j.cmi.2024.03.001. Epub 2024 Mar 8.

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

Anthony Febres-Aldana  1 , Fareed Khawaja  2 , Oscar Morado-Aramburo  2 , Terri Lynn Shigle  3 , Gabriela Rondon  4 , Joseph Sassine  5 , Amy Spallone  2 , Krithika Srinivasan  2 , Jeremy Ramdial  4 , Amin Alousi  4 , Richard Champlin  4 , George Chen  4 , May Daher  4 , Katayoun Rezvani  4 , Ella J Ariza-Heredia  2 , Elizabeth J Shpall  4 , Roy F Chemaly  6
Affiliations

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

Anthony Febres-Aldana et al. Clin Microbiol Infect. 2024 Jun.

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.

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Conflict of interest statement

AFA, OMA, GR, JS, KS, JR and AS have nothing to report.

FK receives research support from Eurofins Viracor. He received an honorarium from WebMD.

TLS has served on the Advisory board for Takeda.

EAH has received research support from Merck.

GC has received research funding from Merck.

EJS serves a s consultant for Mesoblast, Bayer, Novartis, Magenta, Cimeio Therapeutics AG and Celaid Therapeutics. She serves on the Scientific Advisory Board for Synthego Corporation, ASC Therapeutics, Adaptimmune, Navan, Zelluna Immunotherapy, FibroBiologics and Axio.

RFC serves as a consultant, speaker, or scientific advisor for ADMA Biologics, Janssen, Merck/MSD, Partner Therapeutics, Takeda, Shinogi, AiCuris, Roche/Genentech, Astellas, Adagio Therapeutics, Tether, Oxford Immunotec, Karius, and Ansun Pharmaceuticals. He received research grants paid to his institution from Merck/MSD, Karius, AiCuris, Ansun Pharmaceuticals, Takeda, Roche/Genentech, Oxford Immunotec, Freestyle, and Eurofins-Viracor. All other authors have no potential conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.. Cumulative incidence curves of mortality for the D-/R-, R+/LTV-, and R+/LTV+ groups.
(A) All-cause mortality and (B) cumulative incidence of non-relapse mortality with competing incidence of relapse (non-relapse mortality) are demonstrated. Cumulative incidence curves are compared using the Fine and Gray test using the D−/R− group as the reference level in all cases.
See this image and copyright information in PMC

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