EARLY TREATMENT OF CMV INFECTIONS IN ALLOGENEIC BONE-MARROW TRANSPLANT RECIPIENTS WITH FOSCARNET OR GANCICLOVIR

Twenty-five patients with hematologic malignancies (n = 21) or aplasti c anemia (n = 4) undergoing an allogeneic BMT from an HLA-identical si bling developed cytomegalovirus (CMV) antigenemia at a mean interval f rom BMT of 41 days (range 16-141 days). All patients were treated at t he time of antigenemia in the absence of other signs of CMV disease wi th ganciclovir (n = 13) or foscarnet (n = 12) if the WBC count was < 2 .5 x 10(9)/l or the patient had aplastic anemia. The two groups were c omparable for age, sex and disease status. There were more patients re ceiving T cell-depleted grafts in the foscarnet group (58% vs 15%, p = 0.003). The first course of treatment was planned to last a minimum o f 10 days: foscarnet was given at 180 mg/kg/day, and ganciclovir at 10 mg/kg/day. Patients still showing pp65-positive cells continued treat ment in the absence of adverse effects such as cytopenia and/or increa sed creatinine levels. Maintenance treatment was given for 3-4 weeks. End-points of the study were (1) clearing of CMV antigenemia, (2) tole rance and side-effects, and (3) progression to CMV disease. Both agent s were effective in clearing CMV antigenemia: 14 of 25 patients were C MV antigen-negative by day 14 of treatment and all surviving patients were negative by day +50. Renal toxicity was seen mainly in the foscar net group but caused discontinuation of the drug only in one patient. Myelotoxicity was seen in the ganciclovir group and again could be con trolled in 12 of 13 patients. Six patients progressed to develop inter stitial pneumonia (IF), three in each group, and all six died of this complication. The risk of progression was higher in patients receiving T cell-depleted marrow (33% vs 18%, p = 0.3) and for patients not cle aring CMV antigen by day +14 (45% vs 7%; p = 0.09). Survival at 1 year is 62% vs 69% in the foscarnet/ganciclovir groups, respectively (p = 0.9). In conclusion, (1) both drugs are effective in clearing CMV anti genemia, (2) cytopenia and renal toxicity are seen but can be controll ed, and (3) in spite of early treatment some patients may progress to develop CMV disease, especially recipients of a T cell-depleted graft.