Reactivations of Cytomegalovirus, Human Herpes Virus 6, and Epstein-Barr Virus Differ with Respect to Risk Factors and Clinical Outcome after Hematopoietic Stem Cell Transplantation

Abstract

One hundred two recipients of hematopoietic stem cell transplants (HSCTs) 45, from siblings and 57 from matched unrelated donors, were followed for cytomegalovirus (CMV), human herpes virus (HHV) 6, and Epstein-Barr Virus (EBV) reactivation by quantitative polymerase chain reaction in the context of immunologic reconstitution and posttransplantation complications. CMV, EBV, and HHV6 DNA copies (>100 copies/10 5 cells) were detected in 34%, 27%, and 26% of patients, respectively. The presence of 100 copies of EBV or CMV was associated with posttransplant complications: 29/66 versus 6/36 ( P < .01) or 24/66 versus 4/36 ( P = .01). CMV reactivation was more frequent among patients with acute graft-versus-host disease grade ≥I: 17/35 versus 18/67 ( P < .05). Older patient age of adults >16 year (2/16 versus 33/86; P < .05) and, to a lesser extent, CMV IgG positivity before HSCT (34/84 versus 1/10; P = .08) or an HLA-mismatched graft (9/16 versus 26/86; P = .08) constituted risk factors for CMV reactivation, which resulted in a higher rate of bacterial pneumonia (7/11 versus 28/91; P = .04). EBV reactivation risk was associated with donor EBV IgG seropositivity (28/84 versus 0/10; P = .03) and donor female gender (18/47 versus 10/55; P = .03). In contrast to EBV and CMV, EBV reactivation itself was associated with encephalitis (5/8 versus 23/94; P = .013), which was also seen as a trend among HHV6 reactivations (8/8 versus 46/94; P = .08). Multivariate analysis demonstrated that these factors play independent roles in the reactivation of the investigated herpes viruses.