Submitted January 22, 2007
Accepted March 26, 2007
Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis
Francisco M. Marty*, Julie Bryar, Sarah K. Browne, Talya Schwarzberg, Vincent T. Ho, Ingrid V. Bassett, John Koreth, Edwin P. Alyea, Robert J. Soiffer, Corey S. Cutler, Joseph H. Antin, and Lindsey R. Baden
Division of Infectious Diseases, Brigham & Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Division of Medical Oncology, Brigham & Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
* Corresponding author; email: fmarty{at}partners.org.
Sirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of CMV disease. Whether sirolimus has a similar effect on CMV reactivation after allogeneic hematopoietic stem-cell transplantation (HSCT) is not known. We evaluated 606 patients who underwent HSCT between April 2000 and June 2004 to identify risk factors for CMV reactivation 100 days after transplantation. The cohort included 252 patients who received sirolimus-tacrolimus for GVHD prophylaxis; the rest received non-sirolimus-based regimens. An initial positive CMV DNA hybrid capture assay was observed in 225 patients (37.1%) at a median 39 days after HSCT for an incidence rate of 0.50 cases/100 patient-days (95% CI, 0.44-0.57). Multivariable Cox modeling adjusting for CMV donor-recipient serostatus pairs, incident acute GVHD, as well as other important covariates, confirmed a significant reduction in CMV reactivation associated with sirolimus-tacrolimus-based GVHD prophylaxis, with an adjusted HR of 0.46 (95% CI 0.27-0.78, p=0.004). The adjusted HR was 0.22 (95% CI 0.09-0.55, p=0.001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR 0.66, p=0.14 and 0.35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials.
