title: Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis.
abstract: Sirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of cytomegalovirus (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 graft-versus-host disease (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% confidence interval [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 = .004). The adjusted HR was 0.22 (95% CI, 0.09-0.55; P = .001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR, 0.66; P = .14 and P = .35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials.
authors: Division of Infectious Diseases, Boston, MA 02115, USA. fmarty@partners.org
authors: Francisco M
authors: FM
authors: Marty
authors: Julie
authors: J
authors: Bryar
authors: Sarah K
authors: SK
authors: Browne
authors: Talya
authors: T
authors: Schwarzberg
authors: Vincent T
authors: VT
authors: Ho
authors: Ingrid V
authors: IV
authors: Bassett
authors: John
authors: J
authors: Koreth
authors: Edwin P
authors: EP
authors: Alyea
authors: Robert J
authors: RJ
authors: Soiffer
authors: Corey S
authors: CS
authors: Cutler
authors: Joseph H
authors: JH
authors: Antin
authors: Lindsey R
authors: LR
authors: Baden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007938:Leukemia / Q000145:classification / Q000628:therapy; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D012008:Recurrence; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus