Human Herpesvirus-6B Reactivation Is a Risk Factor for Grades II to IV Acute Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

•HHV-6B is associated with aGVHD after allogeneic HCT.•Patients with HHV-6B reactivation are 2 to 3 times more likely than those without to develop aGVHD. Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many...

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Published in:Biology of blood and marrow transplantation 2018-11, Vol.24 (11), p.2324-2336
Main Authors: Phan, Tuan L., Carlin, Kristen, Ljungman, Per, Politikos, Ioannis, Boussiotis, Vicki, Boeckh, Michael, Shaffer, Michele L., Zerr, Danielle M.
Format: Article
Language:English
Subjects:
Acute Disease
Adolescent
Adult
Aged
Female
Graft vs Host Disease - etiology
Graft vs Host Disease - pathology
Graft-versus-host disease
Hematopoietic Stem Cell Transplantation - methods
Herpesvirus 6, Human - pathogenicity
Human herpesvirus-6
Humans
Male
Middle Aged
Neoplasm Grading
Risk factor
Risk Factors
Transplantation Conditioning - methods
Young Adult
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Summary:•HHV-6B is associated with aGVHD after allogeneic HCT.•Patients with HHV-6B reactivation are 2 to 3 times more likely than those without to develop aGVHD. Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that human herpesvirus-6B (HHV-6B) plays a role in acute GVHD (aGVHD) after HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. PubMed and EMBASE databases were searched using terms for HHV-6, HCT, and aGVHD, yielding 865 unique results. Case reports, reviews, articles focusing on inherited chromosomally integrated HHV-6, poster presentations, and articles not published in English were excluded. The remaining 467 articles were reviewed for the following requirements: a statistical analysis of HHV-6B reactivation and aGVHD was described, HHV-6B reactivation was defined by PCR, and blood (plasma, serum, or peripheral blood mononuclear cells) was used for HHV-6B PCR. Data were abstracted from publications that met these criteria (n = 33). Publications were assigned to 1 of 3 groups: (1) HHV-6B reactivation was analyzed as a time-dependent risk factor for subsequent aGVHD (n = 14), (2) aGVHD was analyzed as a time-dependent risk factor for subsequent HHV-6B reactivation (n = 1), and (3) analysis without temporal specification (n = 18). A statistically significant association (P 
ISSN:1083-8791
1523-6536
DOI:10.1016/j.bbmt.2018.04.021