COMBINED FOSCARNET-GANCICLOVIR TREATMENT FOR CYTOMEGALOVIRUS INFECTIONS AFTER ALLOGENEIC HEMATOPOIETIC STEM-CELL TRANSPLANTATION

Citation
A. Bacigalupo et al., COMBINED FOSCARNET-GANCICLOVIR TREATMENT FOR CYTOMEGALOVIRUS INFECTIONS AFTER ALLOGENEIC HEMATOPOIETIC STEM-CELL TRANSPLANTATION, Transplantation, 62(3), 1996, pp. 376-380
Citations number
20
Categorie Soggetti
Immunology,Surgery,Transplantation
Journal title
ISSN journal
00411337
Volume
62
Issue
3
Year of publication
1996
Pages
376 - 380
Database
ISI
SICI code
0041-1337(1996)62:3<376:CFTFCI>2.0.ZU;2-R
Abstract
In a previous study, we showed that patients under-going allogeneic he mopoietic stem cell transplantation (HSCT) who had cytomegalovirus (CM V) antigenemia with more than 4 CMV antigen-positive cells/200,000 hav e a high transplant-related mortality (TRM) rate, despite treatment wi th ganciclovir or foscarnet. In an attempt to reduce TRM, 32 allogenei c HSCT recipients, between the ages of 16 and 55 years (median, 35 yea rs), with CMV antigenemia (greater than or equal to 5 positive cells) developing at a median interval from HSCT of 49 days, were given combi nation treatment with foscarnet and ganciclovir for 15 days. The presc ribed dose was 180 mg/kg/day of foscarnet and 10 mg/kg/day of ganciclo vir: the median administered dose in the first 15 days, after adjustin g for creatinine levels and peripheral blood counts, was 64% for fosca rnet and 53% for ganciclovir. Maintenance was given with foscarnet and ganciclovir on alternate days for an additional 2 weeks. Thirty-one o f 32 patients were on cyclosporine, 30 were on systemic antibiotics, a nd 9 were on intravenous amphotericin. Median laboratory values on day s 1 and 15 of treatment were 1.0 and 1.1 mg/100 ml creatinine, 5.7 x 1 0(9)/L and 4.1 x 10(9)/L white blood cells, and 78 x 1.0(9)/L and 70 x 10(9)/L platelets. All patients cleared CMV antigenemia by day + 15, although CMV antigenemia recurred in 5 patients on maintenance therapy and in 14 patients off maintenance therapy: the dose of foscarnet (bu t not ganciclovir) received in the first 15 days was significantly low er in patients in whom antigenemia recurred within 30 days (P=0.0002). Six patients died , one with interstitial pneumonia, one with multior gan failure, and four with infections. Twenty-six patients survived 11 9-1051 days after transplant. The actuarial TRM rate at 1 year is 23%. Eighteen patients who had received unmanipulated bone marrow transpla nts from HLA-identical sibling were compared with 15 matched controls who had been treated with a single drug (either foscarnet or ganciclov ir) for CMV antigenemia (greater than or equal to 5 cells): the actuar ial 1 year TRM rate was 13% for patients receiving combined treatment, compared with 47% for controls receiving a single drug (P=0.02). This study shows that combined foscarnet-ganciclovir is one therapeutic op tion for allogenic HSCT recipients who develop CMV antigenemia with a high number of CMV antigen-positive cells. Treatment can be given toge ther with cyclosporine and antibiotics with appropriate dose reduction s, It produces prompt clearing of CMV infection, and may reduce TRM ra tes in comparison to single-agent therapy.