CORRELATION BETWEEN HSV-1 RECIPIENT SEROSTATUS AND INCREASED MORTALITY IN A LARGE SINGLE CENTER COHORT OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT (HCT) RECIPIENTS

Background: Although acyclovir prophylaxis has led to major reductions in herpes simplex virus (HSV)-related complications among hematopoietic cell transplant (HCT) recipients, there are no data on the association between HSV serologic status and mortality post-HCT. We sought to compare outcomes in HCT recipients based on pre-transplant HSV-1 and HSV-2 serostatus among a cohort of patients receiving prolonged (minimum 1 year for VZV seropositivity) acyclovir prophylaxis.

Methods: Patients >= 18 years of age receiving their first allogenic transplant at Fred Hutchinson Cancer Research Center (FHCRC) from 2002 – 2012 were included in this retrospective cohort study. HSV serostatus was ascertained by HSV type-specific western blot prior to HCT. Patients were defined as positive for HSV-1, HSV-2, or both. We estimated the effect of survival outcomes at one year post-HCT based on HSV-1 and HSV-2 serostatus using a Cox proportional hazards model with covariates determined a priori including age, sex, graft type, donor relationship, disease risk, conditioning intensity, and Cytomegalovirus serostatus; acute graft-versus-host disease was added as a time dependent covariate.

Results: A total of 2035 adult patients were included in the cohort. The median age at time of transplant was 51 (IQR: 38.4-59.7). The cohort includes 1605 (79%) seropositive for HSV-1, 453 (22%) seropositive for HSV-2 (315 [15%] dual seropositive); 292 [14%] were seronegative for both. A total of 712 persons (35%) died within the first year after transplant. In a univariate model, HSV-1 seropositivity was significantly associated with mortality, (HR=1.32; 95% CI 1.13-1.54; p =0.0004) and this effect remained in a multivariate model (HR 1.35; 95% CI 1.11-1.66; p = .003). HSV-2 seropositivity, however, was neither associated with mortality in a univariate model (HR 1.02; 95% CI 0.88-1.18; p=0.77), nor in a multivariate model (HR 0.91; 95% CI 0.76-1.09; p = 0.31).

Conclusion: These results demonstrate a significant association between HSV-1 seropositivity and mortality in HCT recipients, despite the use of acyclovir prophylaxis in this cohort. Further studies aimed at examining the possible biological mechanisms for causality are warranted.