Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis

Eleftheria Kampouri; Danniel Zamora; Erika S Kiem; Winnie Liu; Sarah Ibrahimi; Rachel L Blazevic; Erika A Lovas; Louise E Kimball; Meei-Li Huang; Keith R Jerome; Masumi Ueda Oshima; Marco Mielcarek; Danielle M Zerr; Michael J Boeckh; Elizabeth M Krantz; Joshua A Hill

doi:10.1016/j.cmi.2023.07.026

Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis

Clin Microbiol Infect. 2023 Jul 31:S1198-743X(23)00354-3. doi: 10.1016/j.cmi.2023.07.026. Online ahead of print.

Authors

Eleftheria Kampouri¹, Danniel Zamora², Erika S Kiem¹, Winnie Liu¹, Sarah Ibrahimi¹, Rachel L Blazevic¹, Erika A Lovas¹, Louise E Kimball¹, Meei-Li Huang³, Keith R Jerome⁴, Masumi Ueda Oshima⁵, Marco Mielcarek⁵, Danielle M Zerr⁶, Michael J Boeckh⁷, Elizabeth M Krantz¹, Joshua A Hill⁸

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
² Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
³ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁴ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁶ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
⁷ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁸ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: Jahill3@fredhutch.org.

PMID: 37532126
PMCID: PMC10828110 (available on 2025-01-31)
DOI: 10.1016/j.cmi.2023.07.026

Abstract

Objectives: Letermovir for cytomegalovirus (CMV) prophylaxis in allogeneic haematopoietic cell transplant (HCT) recipients has decreased anti-CMV therapy use. Contrary to letermovir, anti-CMV antivirals are also active against human herpesvirus-6 (HHV-6). We assessed changes in HHV-6 epidemiology in the post-letermovir era.

Methods: We conducted a retrospective cohort study of CMV-seropositive allogeneic HCT recipients comparing time periods before and after routine use of prophylactic letermovir. HHV-6 testing was at the discretion of clinicians. We computed the cumulative incidence of broad-spectrum antiviral initiation (foscarnet, (val)ganciclovir, and/or cidofovir), HHV-6 testing, and HHV-6 detection in blood and cerebrospinal fluid within 100 days after HCT. We used Cox proportional-hazards models with stabilized inverse probability of treatment weights to compare outcomes between cohorts balanced for baseline factors.

Results: We analysed 738 patients, 376 in the pre-letermovir and 362 in the post-letermovir cohort. Broad-spectrum antiviral initiation incidence decreased from 65% (95% CI, 60-70%) pre-letermovir to 21% (95% CI, 17-25%) post-letermovir. The cumulative incidence of HHV-6 testing (17% [95% CI, 13-21%] pre-letermovir versus 13% [95% CI, 10-16%] post-letermovir), detection (3% [95% CI, 1-5%] in both cohorts), and HHV-6 encephalitis (0.5% [95% CI, 0.1-1.8%] pre-letermovir and 0.6% [95% CI, 0.1-1.9%] post-letermovir) were similar between cohorts. First HHV-6 detection occurred at a median of 37 days (interquartile range, 18-58) in the pre-letermovir cohort and 27 (interquartile range, 25-34) in the post-letermovir cohort. In a weighted model, there was no association between the pre-versus post-letermovir cohort and HHV-6 detection (adjusted hazard ratio, 1.08; 95% CI, 0.44-2.62).

Discussion: Despite a large decrease in broad-spectrum antivirals after the introduction of letermovir prophylaxis in CMV-seropositive allogeneic HCT recipients, there was no evidence for increased clinically detected HHV-6 reactivation and disease.

Keywords: Allogeneic haematopoietic cell transplantation; CMV prophylaxis; HHV-6; Letermovir; Post-transplantation cyclophosphamide.

Abstract

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