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

• Published in: Blood Vol. 130; no. 8; pp. 1062 - 1069
• 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 Elsevier Inc 24.08.2017; American Society of Hematology
• 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; Transplantation; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2017-03-775759

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; P = .004-.001). Cytomegalovirus viremia (any and high-level) was more frequent among recipients with iciHHV-6 (adjusted HRs, 1.7-3.1; P = .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. •Inherited ciHHV-6 was detected in 1.4% of HCT recipients and 0.9% of their donors.•Acute GVHD grades 2-4 and cytomegalovirus viremia were more frequent when recipients or donors had inherited ciHHV-6.