Knoll et al. [1] present a retrospective study of 86 cytomegalovirus (CMV)-seropositive umbilical cord blood transplant (CBT) recipients receiving standard-dose acyclovir/valacyclovir prophylaxis in which they analyzed the incidence of CMV reactivation and disease through day 100 post-CBT. They report that 59% of subjects had any detectable CMV DNA for an overall incidence rate of .69/100 patient-days. Two subjects developed CMV disease, and there were no CMV-attributable deaths. These findings were similar to our reports of CMV reactivation and disease in CBT recipients receiving high-dose acyclovir/valacyclovir prophylaxis, but the incidence appears to be lower than what we reported in CBT recipients receiving standard-dose acyclovir/valacyclovir prophylaxis.
The discrepancy in the incidence of CMV reactivation is likely due in part to the increased sensitivity of our institution’s CMV PCR assay, which resulted in a median initial viral load of 40 IU/mL. Important differences in the characteristics of the cohorts must also be considered in interpreting these findings, including the conditioning regimens, conditioning intensity, and rates of graft-versus-host disease. In particular, sirolimus was used for graft versus host disease prophylaxis in 74% of subjects in the study by Knoll et al. versus in 0% of subjects in our studies, and decreased rates of CMV reactivation are well documented in subjects receiving sirolimus. Although there are potential concerns for toxicity related to high-dose valacyclovir, a large randomized controlled trial using 8000 mg valacyclovir per day after transplant did not demonstrate increased toxicity compared with 3200 mg acyclovir [2], and there was no difference in the proportion of subjects developing acute kidney injury among those receiving a standard versus intensive CMV prophylaxis strategy in our prior study [3].
The data presented by Knoll et al. demonstrate the importance of developing a better understanding of how transplantation practices across institutions affect CMV reactivation risk and associated complications, and prevention strategies can then be customized accordingly. Multicenter studies of sufficient sample size will be important to achieve this goal, particularly with the addition of new prophylactic options.
ACKNOWLEDGMENTS
Financial disclosure: This work was supported by the National Institutes of Health (grants 5K23AI119133-03 to J.A.H. and K24HL093294 to M.B.). Additional resources were provided by the National Institutes of Health (grants HL088021, CA78902, CA18029, HL122173, and P50 HL110787-05).
Footnotes
Conflict of interest statement: J.A.H. has served as a consultant for Chimerix Inc. and Nohla Therapeutics, Inc. and has received research support from Shire, all outside of the submitted work. M.B. reports grants and personal fees from Merck and Co.; grants and personal fees from Astellas, Shire, Roche/Genentech, Gilead, and Chimerix; and personal fees from Clinigen and Microbiotix, outside the submitted work. S.A.P. has served as a consultant for Chimerix and Merck.
REFERENCES
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