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Outcomes of Hematopoietic Cell Transplantation Using Donors or Recipients with Inherited Chromosomally Integrated HHV-6

Overview
Journal Blood
Publisher Elsevier
Specialty Hematology
Date 2017 Jun 10
PMID 28596425
Citations 34
Authors
Affiliations
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Abstract

Human herpesvirus 6 (HHV-6) species have a unique ability to integrate into chromosomal telomeres. Mendelian inheritance via gametocyte integration results in HHV-6 in every nucleated cell. The epidemiology and clinical effect of inherited chromosomally integrated HHV-6 (iciHHV-6) in hematopoietic cell transplant (HCT) recipients is unclear. We identified 4319 HCT donor-recipient pairs (8638 subjects) who received an allogeneic HCT and had archived pre-HCT peripheral blood mononuclear cell samples. We screened these samples for iciHHV-6 and compared characteristics of HCT recipients and donors with iciHHV-6 with those of recipients and donors without iciHHV-6, respectively. We calculated Kaplan-Meier probability estimates and Cox proportional hazards models for post-HCT outcomes based on recipient and donor iciHHV-6 status. We identified 60 HCT recipients (1.4%) and 40 donors (0.9%) with iciHHV-6; both recipient and donor harbored iciHHV-6 in 13 HCTs. Thus, there were 87 HCTs (2%) in which the recipient, donor, or both harbored iciHHV-6. Acute graft-versus-host disease (GVHD) grades 2-4 was more frequent when recipients or donors had iciHHV-6 (adjusted hazard ratios, 1.7-1.9; = .004-.001). Cytomegalovirus viremia (any and high-level) was more frequent among recipients with iciHHV-6 (adjusted HRs, 1.7-3.1; = .001-.040). Inherited ciHHV-6 status did not significantly affect risk for chronic GVHD, hematopoietic cell engraftment, overall mortality, or nonrelapse mortality. Screening for iciHHV-6 could guide donor selection and post-HCT risk stratification and treatment. Further study is needed to replicate these findings and identify potential mechanisms.

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References
1.
Martin P, McDonald G, Sanders J, Anasetti C, Appelbaum F, Deeg H . Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2004; 10(5):320-7. DOI: 10.1016/j.bbmt.2003.12.304. View

2.
Hill J, Mayer B, Xie H, Leisenring W, Huang M, Stevens-Ayers T . The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality. Blood. 2017; 129(16):2316-2325. PMC: 5399484. DOI: 10.1182/blood-2016-10-748426. View

3.
Engdahl E, Dunn N, Niehusmann P, Wideman S, Wipfler P, Becker A . Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration. J Virol. 2017; 91(11). PMC: 5432873. DOI: 10.1128/JVI.02105-16. View

4.
Hill J, Zerr D . Roseoloviruses in transplant recipients: clinical consequences and prospects for treatment and prevention trials. Curr Opin Virol. 2014; 9:53-60. PMC: 4570620. DOI: 10.1016/j.coviro.2014.09.006. View

5.
Huang Y, Hidalgo-Bravo A, Zhang E, Cotton V, Mendez-Bermudez A, Wig G . Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome. Nucleic Acids Res. 2013; 42(1):315-27. PMC: 3874159. DOI: 10.1093/nar/gkt840. View