A pilot phase II study of alternate day ganciclovir and foscarnet in preventing cytomegalovirus (CMV) infections in at-risk pediatric and adolescent allogeneic stem cell transplant recipients.

Background: Prophylaxis with ganciclovir or foscarnet post allogeneic stem cell transplant (AlloSCT) reduces cytomegalovirus (CMV) disease. Combination ganciclovir/foscarnet is more effective than monotherapy in HIV patients with CMV retinitis. We hypothesized that alternate day ganciclovir and foscarnet for the prevention of CMV during the first 100 days after AlloSCT would be safe and effective.

Procedure: Fifty-three pediatric and adolescent AlloSCT recipients receiving 57 AlloSCTs where donors and/or recipients were CMV seropositive received ganciclovir (5 mg/kg/48 hr) alternating with foscarnet (90 mg/kg/48 hr) from myeloid recovery (>or=ANC 750/mm3) until Day +100.

Results: Patients were: M:F 31:22; age 6 years (0.8-18 years); donor sources: 25 related peripheral blood/bone marrow, 3 unrelated adult peripheral blood, 26 unrelated cord blood, and 3 related cord blood. GVHD prophylaxis included tacrolimus/mycophenolate mofetil (MMF). Median-nucleated and CD34 cell counts were 7.3x10(8)/kg and 5.07x10(6)/kg, respectively, for BM/PBSC; 4.07x10(7)/kg and 1.69x10(5)/kg, respectively, for CB. Despite a 36.5% probability of Grades II-IV acute GVHD, no patient developed systemic CMV disease. Five percent had Grade IV hematological toxicity that required discontinuation of ganciclovir. Twenty-five percent required discontinuation of foscarnet secondary to electrolyte abnormalities and/or renal dysfunction that were presumed to be multifactorial in origin. Probability of 1-year overall survival was 58.8%.

Conclusions: Alternate day ganciclovir/foscarnet in AlloSCT recipients where recipient and/or donor is seropositive appears to be tolerable and 100% effective in preventing CMV systemic disease. A randomized study will be required to determine if this approach is superior to other CMV prophylactic designs.