Cytomegalovirus Immunoglobulin for Prophylaxis and Treatment of Cytomegalovirus Infection in the (Val)Ganciclovir Era: A Single-Center Experience
Cristina Lopez Garcia-Gallo, Christian García Fadul, Rosalia Laporta, Francisca Portero, Isabel Millan, Piedad Ussetti
Department of Pulmonology, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain
Ann Transplant 2015; 20:661-666
Available online: 2015-11-05
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 >38oC), 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.
Keywords: Cytomegalovirus, Cytomegalovirus Infections, Ganciclovir, Immunoglobulins, Lung Transplantation