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

Abstract Background/Objective Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that HHV-6B plays a role in acute GVHD (aGVHD) following HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. Methods 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 papers were reviewed for the following requirements: (i) a statistical analysis of HHV-6B reactivation and aGVHD was described, (ii) HHV-6 reactivation was defined by PCR, and (iii) blood (plasma, serum or PBMCs) was used for HHV-6B PCR. Data were abstracted from publications that met these criteria (n=33). Publications were assigned to one of 3 groups: (1) HHV-6B reactivation was analyzed as a time-dependent risk factor for subsequent aGVHD (n=14), (2) aGVHD analyzed as a time-dependent risk factor for subsequent HHV-6B reactivation (n=1), and (3) analysis without temporal specification (n=18). Results A statistically significant association (p Conclusion HHV-6B reactivation is associated with aGVHD, and when studies have a temporal component to their design, HHV-6B reactivation is associated with subsequent aGVHD. Further research is needed to investigate whether antiviral prophylaxis reduces incidence or severity of aGVHD.