Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection.
Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D015658:HIV Infections / Q000097:blood / Q000628:therapy*; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils; D010865:Pilot Projects; D010976:Platelet Count; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D016179:Granulocyte Colony-Stimulating Factor; D015215:Zidovudine