title: Combination prophylaxis with ganciclovir and cytomegalovirus (CMV) immune globulin after lung transplantation: effective CMV prevention following daclizumab induction.
abstract: Despite the serious direct and indirect deleterious effects caused by cytomegalovirus (CMV), the optimal prophylactic strategy remains unknown. We sought to determine whether combination prophylaxis using intravenous ganciclovir (GCV) and CMV-IVIG reduced the incidence of CMV compared to GCV alone. Donor CMV positive/recipient negative (D+/R-) patients received GCV (6 weeks i.v. + 6 weeks oral) and CMV-IVIG (every 2 weeks for 7 doses), while R+ patients received GCV (2 weeks i.v. + 4 weeks oral) and CMV-IVIG (every 2 weeks for 3 doses). The group receiving combination prophylaxis (GpA) was compared to a historical, case-controlled group receiving GCV alone (GpB). Groups were matched by CMV donor/recipient serology, pretransplant diagnosis, age, and sex in reverse chronological order. Cyclosporine, azathioprine, and prednisone were used in both groups. Additionally, GpA received daclizumab induction therapy. Groups were compared as to the incidence of CMV disease, CMV infection, and acute rejection (AR). In GpA, 38 patients were evaluable and matched to 48 patients in GpB. Three GpA patients (8%) (2 D+/R-) developed CMV disease vs. 16 patients (33%) in GpB, p = 0.0077, Fisher's exact. There was also a trend toward a delay in CMV onset (148 days in GpA vs. 92 days in GpB, p = 0.07, Mann-Whitney). CMV infection did not occur in GpA, and one case occurred in GpB. There was no difference in the incidence of AR (66% in GpA vs. 79% in GpB, p = 0.22, Fisher's exact) or the need for cytolytic therapy between groups. Despite the use of daclizumab induction therapy, combination prophylaxis with GCV and CMV-IVIG reduced the incidence and probably delayed the onset of CMV infection compared to GCV alone. Longer follow-up will be needed to evaluate the impact of combination therapy on the incidence of bronchiolitis obliterans syndrome (BOS).
authors.affiliation: Department of Medicine and Cardiothoracic Surgery,Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, AL, USA. david.weill@uchsc.edu
authors.forename: David
authors.initials: D
authors.lastname: Weill
authors.forename: Brion J
authors.initials: BJ
authors.lastname: Lock
authors.forename: Donavon L
authors.initials: DL
authors.lastname: Wewers
authors.forename: K Randall
authors.initials: KR
authors.lastname: Young
authors.forename: George L
authors.initials: GL
authors.lastname: Zorn
authors.forename: Lesley
authors.initials: L
authors.lastname: Early
authors.forename: James K
authors.initials: JK
authors.lastname: Kirklin
authors.forename: David C
authors.initials: DC
authors.lastname: McGiffin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use*; D006084:Graft Rejection; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D007136:Immunoglobulins / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D007074:Immunoglobulin G; D007136:Immunoglobulins; D000077561:Daclizumab; D015774:Ganciclovir