Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6

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 c...

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Published in:Blood Vol. 130; no. 8; p. 1062
Main Authors: Hill, Joshua A, Magaret, Amalia S, Hall-Sedlak, Ruth, Mikhaylova, Anna, Huang, Meei-Li, Sandmaier, Brenda M, Hansen, John A, Jerome, Keith R, Zerr, Danielle M, Boeckh, Michael
Format: Journal Article
Language:English
Published: United States 24.08.2017
Subjects:
Acute Disease
Adult
Chromosomes, Human - genetics
Chromosomes, Human - virology
Chronic Disease
Female
Graft vs Host Disease - genetics
Hematopoietic Stem Cell Transplantation
Herpesvirus 6, Human - genetics
Humans
Incidence
Inheritance Patterns - genetics
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Probability
Proportional Hazards Models
Risk Factors
Tissue Donors
Treatment Outcome
ISSN:1528-0020, 1528-0020
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Summary: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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ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2017-03-775759