allopurinol and Candidiasis

Infection during the induction phase of childhood acute lymphoblastic leukemia (ALL) is a major cause of morbidity and mortality. Several studies have indicated that genetically determined low serum levels of mannose-binding lectin (MBL), a component of innate immunity, are associated with increased risk for infections in patients receiving chemotherapy. Thus, these patients have been proposed to be candidates for MBL replacement therapy.. In a population-based cohort of 137 children with ALL treated at a single pediatric hematology-oncology center with an almost identical chemotherapy regimen, we studied the relationship between polymorphisms in the MBL gene (MBL2) and the MBL2 promoter and the risk of infections during the first 50 d of induction therapy.. No increased frequency of infection was seen for the children with genotypes encoding serum low levels of MBL. A higher incidence of fever (P < 0.004), infectious events (P = 0.025), days with neutropenia (P < 0.001) and a higher frequency of antimicrobial therapy (P = 0.0007) were seen in the young age group (<2.5 yr) compared with the older age group (> or =2.5 yr), independent of the MBL genotype.. MBL deficiency did not influence the frequency of infections in children receiving induction chemotherapy for ALL, not even in the youngest children (<2.5 yr) whom we found to have the highest risk for infections.

Topics: Adolescent; Age Factors; Allopurinol; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Candidiasis; Child; Child, Preschool; Cohort Studies; Disease Susceptibility; Doxorubicin; Female; Fever; Fungemia; Genotype; Humans; Immunity, Innate; Immunocompromised Host; Incidence; Infant; Infections; Male; Mannose-Binding Lectin; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Promoter Regions, Genetic; Remission Induction; Vincristine

A new type of antibody-enzyme conjugate was made, and its possible application to Candida infection was studied. Both lactoperoxidase and xanthine oxidase were conjugated to specific antibody against Candida albicans. In vitro microbiocidal activity of the new antibody-enzyme conjugate, when incubated together with xanthine and minute amount of halides, showed a remarkable level of candidacidal ability. When the new antibody-enzyme conjugate was given to Candida-infected mice, followed by injecting xanthine and a minute amount of halides, about 50% of these heavily infected mice survived, whereas all control nontreated mice died. These data suggest that the further eleboration of this new antibody-enzyme conjugate might lead us to improve our therapeutic methods of clinical medicine.

Topics: Animals; Antibodies, Fungal; Candida albicans; Candidiasis; Iodides; Lactoperoxidase; Male; Mice; Mice, Inbred C3H; Peroxidases; Xanthine Oxidase; Xanthines