Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis

Mitsani, Dimitra; Nguyen, M. Hong; Kwak, Eun J.; Silveira, Fernanda P.; Vadnerkar, Aniket; Pilewski, Joseph; Crespo, Maria; Toyoda, Yoshiya; Bermudez, Christian; Clancy, Cornelius J.

doi:10.1016/j.healun.2010.04.022

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 29, Issue 9 , Pages 1014-1020, September 2010

Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis

Dimitra Mitsani, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
M. Hong Nguyen, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
Eun J. Kwak, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
Fernanda P. Silveira, MD, MS
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
Aniket Vadnerkar, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
Joseph Pilewski, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
Maria Crespo, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
Yoshiya Toyoda, MD, PhD
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
Christian Bermudez, MD
- Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
Cornelius J. Clancy, MD
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
- Department of Medicine, Pittsburgh VA Healthcare System, Pittsburgh, PA
- Reprint requests: Cornelius J. Clancy, MD, University of Pittsburgh, Infectious Diseases, 3550 Terrace St, Scaife Hall, Ste. 871, Pittsburgh, PA 15261. Telephone: 412-383-5193. Fax: 412-648-8455

published online 05 July 2010.

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.

Keywords: cytomegalovirus, valganciclovir, lung transplantation, D+/R-, alemtuzumab, risk factors