Cytomegalovirus Immunoglobulin for Prophylaxis and Treatment of Cytomegalovirus Infection in the (Val)Ganciclovir Era: A Single-Center Experience

Ann Transplant. 2015 Nov 5:20:661-6. doi: 10.12659/aot.894694.

Abstract

Background: Evidence concerning the effectiveness of anti-cytomegalovirus immunoglobulin (CMVIg) following lung transplantation in the era of new antiviral agents is limited and controversial.

Material and methods: At-risk patients (donor seropositive/recipient seronegative [D+/R-] and R+) received valganciclovir for 3 months (R+) or 6 months (D+/R). CMVIg (2 mg/kg) was given to D+/R- patients on days 1, 4, 8, 15, and 30 post-transplant, then monthly for a further year. Patients with valganciclovir-induced leukopenia were switched to CMVIg (2 mg/kg) prophylaxis. Tissue-invasive disease was treated with intravenous ganciclovir with CMVIg (2 mg/kg) every other day for 1 week and then weekly until discharge.

Results: Of 159 patients analyzed, 26 (17%) were D+/R-. Cytomegalovirus (CMV) viremia was more frequent in D+/R- recipients than in R+ patients (61% vs. 35%; P<0.05), but developed at a similar time (mean 10±6 vs. 11±7 months) and resolved in all cases following treatment. One patient developed clinical and laboratory signs of CMV syndrome (fever >38°C), leukopenia, and detection of CMV in blood. Ten patients developed tissue-invasive disease after completion of prophylaxis (5 pneumonitis and 5 gastrointestinal disease); all were successfully treated with combined intravenous ganciclovir and CMVIg. None of the 18 donor seropositive/recipient seronegative patients who were switched from valganciclovir to CMVIg for persistent leukopenia developed CMV viremia during treatment. No cases of CMV infection or disease were attributable to ganciclovir-resistant strains. During follow-up, 44 patients died (4/26 R+/D- [15%], 40/133 R+ [30%), none directly due to CMV infection.

Conclusions: Combined prophylaxis with valganciclovir and CMVIg delayed CMV viremia and tissue-invasive disease in D+/R- lung transplant recipients, and prevented CMV-related mortality and development of ganciclovir resistance. CMVIg monotherapy prophylaxis was effective in R+ patients with ganciclovir-related toxicity.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / prevention & control*
  • Female
  • Ganciclovir / analogs & derivatives
  • Graft Rejection / prevention & control*
  • Humans
  • Immunoglobulins / therapeutic use*
  • Immunoglobulins, Intravenous
  • Lung Transplantation
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Valganciclovir
  • Young Adult

Substances

  • Antiviral Agents
  • Immunoglobulins
  • Immunoglobulins, Intravenous
  • cytomegalovirus-specific hyperimmune globulin
  • Valganciclovir
  • Ganciclovir