ABSTRACT
A retrospective study was performed to collect information regarding efficacy and toxicity of cidofovir (CDV) in allogeneic stem cell transplant patients. Data were available on 82 patients. The indications for therapy were cytomegalovirus (CMV) disease in 20 patients, primary preemptive therapy in 24 patients, and secondary preemptive therapy in 38 patients. Of the patients, 47 had received previous antiviral therapy with ganciclovir, foscarnet, or both drugs. The dosage of CDV was 1 to 5 mg/kg per week followed by maintenance every other week in some patients. The duration of therapy ranged from 1 to 134 days (median, 22 days). All patients received probenecid and prehydration. Ten of 20 (50%) patients who were treated for CMV disease (9 of 16 with pneumonia) responded to CDV therapy, as did 25 of 38 (66%) patients who had failed or relapsed after previous preemptive therapy and 15 of 24 (62%) patients in whom CDV was used as the primary preemptive therapy. Of the patients, 21 (25.6%) developed renal toxicity that remained after cessation of therapy in 12 patients. Fifteen patients developed other toxicities that were potentially due to CDV or the concomitantly given probenecid. No toxicity was seen in 45 (61.6%) patients. Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy. However, additional studies are needed before CDV can be recommended for preemptive therapy.
Subject(s)
Cytomegalovirus Infections/drug therapy , Cytosine/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Organophosphonates , Organophosphorus Compounds/administration & dosage , Adolescent , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/standards , Antiviral Agents/toxicity , Child , Child, Preschool , Cidofovir , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Cytosine/analogs & derivatives , Cytosine/standards , Cytosine/toxicity , Data Collection , Drug Evaluation , Humans , Infant , Male , Middle Aged , Organophosphorus Compounds/standards , Organophosphorus Compounds/toxicity , Renal Insufficiency/chemically induced , Renal Insufficiency/virology , Retrospective Studies , Survival Rate , Transplantation, Homologous/adverse effects , Treatment OutcomeABSTRACT
A sensitive assay for 5-methylcytosine in DNA has been developed based on stable isotope dilution gas chromatography-mass spectrometry with selected ion monitoring. 5-[( 2H3]-Methyl)cytosine and [methyl-2H3]thymine have been synthesized as internal standards for analysis of DNA following acid digestion, conversion of pyrimidines to volatile t-butyldimethylsilyl derivatives, and separation in 3 min by gas chromatography. Submicrogram amounts of DNA have been analyzed for 5-methylcytosine content in the range 0.02-1.5 mol%. The estimated limit of quantitative measurement is 0.3 pmol of methylated base in a DNA hydrolysate. The method is compared with other techniques for quantitative measurement of methylated bases in DNA, and 5-methylcytosine levels and precision of analysis for calf thymus, pBR322, and phi X-174 DNAs are reported and compared with literature values. The method can readily be adapted to the accurate high-sensitivity analysis of other methylated bases in DNA.
