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.
Red blood cell depletion and cryopreservation of umbilical cord blood (UBC)
