Double Umbilical Cord Blood Transplant Patients Have a Higher Risk of HHV-6 Infection.

Abstract

By age 2 years, 90% of children will have had primary infection with human herpesvirus 6 (HHV-6), which then becomes latent. HHV-6 can subsequently reactivate and cause disease in an immunosuppressed person. To investigate the effect of high-dose acyclovir as a prophylaxis against HHV-6 infection and to investigate the risk factors for having a positive HHV-6 quantitative polymerase chain reaction (PCR) assay, we identified a cohort of hematopoietic cell transplant (HCT) patients who had clinical indications for obtaining a HHV-6 PCR assay from 2003–2005 and evaluated their prospectively collected data. A total of 442 patients, including children and adults, obtained a hematopoietic cell transplantation from 2003–2005. Of this cohort, 137 were tested for HHV-6 with a PCR assay (median age 19 years; range 0.3–68 years). A positive HHV-6 PCR assay was found in 38 of the patients. The cell source included single (n=26) or double umbilical cord blood (UCBT, n=67), bone marrow (BM, n=25) and peripheral blood (PB, n=19). The median age was not significantly different for patients who tested positive compared to those patients who tested negative for HHV-6. About 50% of the patients received high-dose acyclovir. There was no significant difference in the cumulative incidence of a positive HHV-6 PCR assay by post-transplant day 100 in patients who received high-dose acyclovir (1500mg/m2/day) compared to those who did not receive high-dose acyclovir (p=0.8). Double umbilical cord blood transplant patients had 6 times higher risk of a positive HHV-6 PCR assay compared to BM or PB transplant patients, after adjusting for the transplant conditioning regimen (Hazard ratio=6.2, 95%CI 1.79–21.35, p=0.004). Compared to single UCBT patients, double UCBT patients still had 2 times higher risk of a positive HHV-6 PCR assay (95%CI 1.1– 7.4, p=0.03). For double UCBT, a significantly higher rate of positive HHV-6 PCR assay was found for those patients who received a myeloablative conditioning regimen compared to a non-myeloablative regimen (p=0.01). The use of Fludarabine was not significantly different between myeloablative and non-myeloablative conditioning regimens in those patients who received a double UCBT. In summary, we did not find statistical evidence that high-dose acyclovir was an effective prophylaxis against HHV-6 infection, though the analysis may be hampered by low power. We did find that double umbilical cord blood transplant patients are at high risk of having a positive HHV-6 PCR assay compared to BM, PB and single UCBT patients. The underlying reason for this increased risk is unclear and further investigation will be clinically valuable.