A. Bacigalupo et al., COMBINED FOSCARNET-GANCICLOVIR TREATMENT FOR CYTOMEGALOVIRUS INFECTIONS AFTER ALLOGENEIC HEMATOPOIETIC STEM-CELL TRANSPLANTATION, Transplantation, 62(3), 1996, pp. 376-380
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.