title: Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis.
abstract: BACKGROUND
  Valganciclovir prophylaxis is advocated for lung transplant recipients, but its efficacy is unknown.
  
  
  METHODS
  Retrospective review was done of 109 donor-positive/recipient-negative lung transplant patients who received alemtuzumab induction and valganciclovir for cytomegalovirus prophylaxis.
  
  
  RESULTS
  Median duration of follow-up after transplant was 27 months. Valganciclovir dose reductions (< 900 mg/day or renal-equivalent) were required for 18 patients (17%) due to toxicity, most commonly for neutropenia (n = 15) or gastrointestinal symptoms (n = 2). Of the 109 patients, 34 (31%) had no CMV infections, 45 (41%) had asymptomatic viremia, and 30 (27%) had CMV disease. CMV disease developed off prophylaxis in 10 patients (18%) at a median of 8.7 months after transplant and 2 months after valganciclovir discontinuation. Breakthrough disease occurred during prophylaxis in 10 patients (9%) at a median of 6.7 months. Patients with asymptomatic viremia or no CMV infection received prophylaxis for median 8.6 and 8.7 months, respectively. Risk factors for CMV disease by univariate analysis were increased age (p = 0.01), single-lung transplant (p = 0.03), chronic obstructive pulmonary disease (p = 0.05), reduced-dose valganciclovir (p = 0.001), and less than 6 months of prophylaxis (p = 0.005). By multivariate analysis, advanced age (p = 0.01) and reduced-dose valganciclovir (p = 0.0006) were independent risk factors for CMV disease. CMV disease developed in 4 patients (4%) due to ganciclovir-resistant viruses. CMV-attributable mortality was 5% (5 of 109), including 100% (4 of 4) with ganciclovir-resistant disease.
  
  
  CONCLUSIONS
  Valganciclovir prophylaxis among donor-positive/recipient-negative lung transplant recipients delayed but did not eliminate CMV disease or CMV-related deaths and was limited by toxicity and ganciclovir-resistance. Our experience suggests that valganciclovir at reduced-doses or for less than 6 months is sub-optimal in preventing CMV disease.
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Mitsani
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Kwak
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Silveira
authors.forename: Aniket
authors.initials: A
authors.lastname: Vadnerkar
authors.forename: Joseph
authors.initials: J
authors.lastname: Pilewski
authors.forename: Maria
authors.initials: M
authors.lastname: Crespo
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Christian
authors.initials: C
authors.lastname: Bermudez
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000517:prevention & control / Q000635:transmission; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control; D016041:Heart-Lung Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use; D012086:Reoperation / Q000706:statistics & numerical data; D012189:Retrospective Studies; D017741:Survivors; D013997:Time Factors; D014019:Tissue Donors; D014230:Triazoles / Q000627:therapeutic use; D000077562:Valganciclovir; D065819:Voriconazole
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D000074323:Alemtuzumab; D000077562:Valganciclovir; D065819:Voriconazole; D015774:Ganciclovir