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Meta-Analysis
. 2024 Dec;59(12):1683-1693.
doi: 10.1038/s41409-024-02398-w. Epub 2024 Sep 8.

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

Christopher J Stathis #  1   2 , Harrison Zhu #  2   3 , Kristen Carlin  4 , Tuan L Phan  2   5 , Danny Toomey  2   6 , Joshua A Hill  7   8   9 , Danielle M Zerr  10
Affiliations
Meta-Analysis

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

Christopher J Stathis et al. Bone Marrow Transplant. 2024 Dec.

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.

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Conflict of interest statement

Competing interests: CS, HZ, KC, TP, and DT have no conflicts to disclose. JAH provides consulting for Allovir, Gilead, Karius, Symbio, and receives research support from Allovir, Gilead, Karius, and Merck. DMZ received research funding from Merck and served as a consultant for AlloVir by serving on clinical endpoint adjudication committees for two studies. Ethics approval and consent to participate: Our study is exempt from IRB approval as all data is publicly available.

Figures

Fig. 1
Fig. 1
PRISMA Flowchart.
Fig. 2
Fig. 2
a Non relapse mortality associated with HHV-6 positivity: Random effects model. b Non relapse mortality associated with HHV-6 positivity: Bayesian Aggregation.
Fig. 3
Fig. 3
a Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Stem Cell Source. b Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Age. c Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Follow-up Period.
Fig. 3
Fig. 3
a Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Stem Cell Source. b Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Age. c Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Follow-up Period.
Fig. 3
Fig. 3
a Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Stem Cell Source. b Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Age. c Risk of Overall Mortality with HHV-6 Positivity, Subgroup analysis by Follow-up Period.
Fig. 4
Fig. 4
Funnel Plot of Studies evaluating Overall Mortality.
See this image and copyright information in PMC

References

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