Foscarnet prophylaxis of cytomegalovirus infections in patients undergoingallogeneic bone marrow transplantation (BMT): a dose-finding study

This is a dose-finding study using,foscarnet for CMV prophylaxis after allo geneic bone marrow transplantation (BMT) in 20 high risk patients (unrelate d donors, or T cell depleted, and/or advanced disease). Foscarnet was start ed on day +1 after BMT and continued until day +100, We explored four diffe rent dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positi ve CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/d ay between days 1 and 30 (induction) and between days 31 and 100 (maintenan ce) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6. All patients showed engraftment: PMN greater than or equal to 0.5 x 10(9 )/l at a median interval of 16, 21, 17, 15 days after BMT, and Pit greater than or equal to 30 x 10(9)/l on days 19,16, 17, 17 respectively. CMVAg-emi a was seen in 10 patients at a median interval of 53 days post-BMT (range 3 3-89) with a median of 10 CMV antigen+ cells (range 1-16), There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (5 0%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV d isease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels I II, IV (P = 0.07), The median number of CMV antigen-positive cells at diagn osis of CMV infection was different: 13 in dose levels I-II and two in dose levels m-Iv (P = 0.01), Increased creatininine was seen in 15 patients wit h a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. O verall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I- II and 19% for patients at dose levels III-IV. hi conclusion, foscarnet exh ibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and t ransplant-related mortality with acceptable and reversible renal toxicity.