Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients.

The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

The effects of cidofovir 1% with and without cyclosporin a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study.

OBJECTIVE: To evaluate the efficacy of cidofovir 1% eyedrops with and without cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis (AKC). DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four patients with acute adenoviral keratoconjunctivitis of recent onset. METHODS: Patients were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir 10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily, and 4) sodium chloride four times daily (control). The diagnosis was confirmed by adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME MEASURES: Severity of conjunctival injection, conjunctival chemosis, punctate epithelial keratitis during the course of treatment, and presence and severity of corneal subepithelial infiltrates were evaluated by a clinical score. Duration until subjective improvement of symptoms was recorded. RESULTS: The frequency of severe corneal opacities was lower with cidofovir (P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were clinically similar to the signs of the initial viral inflammation. They first appeared 8 to 12 days after beginning of treatment and completely subsided 7 to 28 days after discontinuation of cidofovir. The outcome measures of local inflammation did not differ between the four treatment groups. Cyclosporin A did not alter the course of the infection. CONCLUSIONS: Cidofovir lowers the frequency of severe corneal opacities, but its clinical use 4 to 10 times daily at a 1% concentration is limited by local toxicity. Further clinical studies to find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an improved pharmaceutical preparation, are required.