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

被引:53
作者
Hill, Joshua A. [1 ,2 ]
Magaret, Amalia S. [2 ,3 ,4 ]
Hall-Sedlak, Ruth [3 ]
Mikhaylova, Anna [4 ]
Huang, Meei-Li [3 ]
Sandmaier, Brenda M. [1 ,5 ]
Hansen, John A. [1 ,5 ]
Jerome, Keith R. [2 ,3 ]
Zerr, Danielle M. [1 ,6 ]
Boeckh, Michael [1 ,2 ]
机构
[1] Univ Washington, Dept Med, Seattle, WA USA
[2] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis, Seattle, WA 98109 USA
[3] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA
[4] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[5] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA
[6] Univ Washington, Dept Pediat, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
HUMAN-HERPESVIRUS; 6; VERSUS-HOST-DISEASE; HUMAN-HERPESVIRUS-6; REACTIVATION; IDENTIFICATION; MUTATIONS; VIRUS;
D O I
10.1182/blood-2017-03-775759
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1062 / 1069
页数:8
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