Successful preemptive cidofovir treatment for CMV antigenemia after dose-reduced conditioning and allogeneic blood stem cell transplantation

Background Cidofovir (CDV) is a nucleotide analogue with proven in vitro ef fects against cytomegalovirus (CMV) and adenovirus and has been successfull y used in the treatment of CMV retinitis in AIDS patients. Methods. We performed a prospective study to evaluate the efficacy of CDV i n 17 patients with hematological malignancies after allogeneic blood stem c ell transplantation from related (n=3) and unrelated (n=14) donors. Dose-re duced conditioning (DRC) regimen consisted of busulfan (Bu)/fludarabine (Fl u) (n=9) and idarubicin/cytosine arabinoside/Flu (n=1). Myeloablative condi tioning (MC) was performed with Bu/cyclophosphamide (Cy)/etoposide (Eto) (n =4), Bu/Cy (n=2), and total body irradiation (TBI)/Cy/Eto (n=1). Antithymoc yte globulin (ATG) was used in seven patients with DRC and in six patients with MC. In all patients, either the donor, host, or both were CMV IgG posi tive pretransplant. Indication for therapy was preemptive treatment of prim ary CMV antigenemia defined as two consecutive positive tests of pp65 antig enemia assay after transplant. In case of response with a decreasing number of pp65-positive leukocytes, CDV was scheduled in a dosage of 5 mg/kg body weight once a week for 2 weeks followed by maintenance therapy every 2 wee ks in an outpatient setting. All patients received probenecid and prehydrat ion as recommended. Patients were monitored using an immunostaining assay f or pp65 antigen and a qualitative and quantitative CMV polymerase chain rea ction (PCR). Success of treatment was defined as negativity for the pp65 an tigen. Results. After DRC, nine of ten patients (90%) showed a response with seven of nine revealing a complete clearance of the virus (pp65 negative, qualit ative PCR negative). In the remaining two responders, treatment was changed to ganciclovir because of either renal impairment or slow clearance of ant igenemia. Only one of seven patients in the MC group experienced a temporar y clearance of pp65 antigen. After MC, two patients experienced CMV disease . Treatment-related toxicity rate was moderate with four patients developin g reversible renal impairment (creatinine 133-180 mu mol/L); one patient wi th proteinuria and three patients with complaints of nausea and vomiting. Conclusion. Our data suggest the feasibility of CDV administration in patie nts after allogeneic transplantation, In the recommended dose, it might be used successfully for low-risk patients, e.g., after DRC or organ transplan tation, in an outpatient setting.