A systematic review and meta-analysis of HHV-6 and mortality after hematopoietic cell transplant

Christopher J Stathis; Harrison Zhu; Kristen Carlin; Tuan L Phan; Danny Toomey; Joshua A Hill; Danielle M Zerr

doi:10.1038/s41409-024-02398-w

A systematic review and meta-analysis of HHV-6 and mortality after hematopoietic cell transplant

Bone Marrow Transplant. 2024 Sep 8. doi: 10.1038/s41409-024-02398-w. Online ahead of print.

Authors

Christopher J Stathis^#^{1

2}, Harrison Zhu^#^{2

3}, Kristen Carlin⁴, Tuan L Phan^{2

5}, Danny Toomey^{2

6}, Joshua A Hill^{7

8

9}, Danielle M Zerr¹⁰

Affiliations

¹ Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² HHV-6 Foundation, Santa Barbara, CA, 93108, USA.
³ Baylor College of Medicine, Houston, TX, USA.
⁴ Seattle Children's Research Institute, Seattle, WA, USA.
⁵ Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁶ Geisinger Commonwealth School of Medicine, Scranton, PA, 18509, USA.
⁷ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁸ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁹ Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁰ Seattle Children's Research Institute and Department of Pediatrics, University of Washington, Seattle, WA, USA. Danielle.zerr@seattlechildrens.org.

^# Contributed equally.

PMID: 39245683
DOI: 10.1038/s41409-024-02398-w

Abstract

Human herpesvirus-6B (HHV-6B) reactivation has been associated with non-relapse mortality (NRM) and overall mortality (OM) following allogeneic hematopoietic stem cell transplant (HCT). We performed a systematic review and meta-analysis to better quantify the association. Studies were included if they systematically tested a cohort of HCT recipients for HHV-6 infection or reactivation and described mortality for patients with and without HHV-6B. Random effects models were used to assess the pooled effect of HHV-6B positivity on each outcome of interest. Bayesian aggregation was additionally performed if models included 10 or fewer studies. Eight studies were included in the NRM analysis, which demonstrated a significant association between HHV-6 detection and NRM (pooled effect: 1.84; 95% CI: 1.29-2.62) without significant heterogeneity (I² = 0.0%, p = 0.55). A Bayesian aggregation of the raw data used to construct the NRM random effects model supported these findings (95% credible interval: 0.15-1.13). Twenty-five studies were included in OM analysis, which showed a significant positive association (pooled effect: 1.37; 95% CI: 1.07-1.76), though considerable heterogeneity was observed (I² = 36.7%, p < 0.05). HHV-6 detection is associated with NRM and OM following HCT. Randomized trials are warranted to evaluate if preventing or treating HHV-6B reactivation improves outcomes.