Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection

J Pediatr. 1992 Nov;121(5 Pt 1):797-802. doi: 10.1016/s0022-3476(05)81918-3.

Abstract

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.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • HIV Infections / blood
  • HIV Infections / therapy*
  • Humans
  • Infant
  • Leukocyte Count
  • Male
  • Neutrophils
  • Pilot Projects
  • Platelet Count
  • Zidovudine / administration & dosage*
  • Zidovudine / adverse effects

Substances

  • Granulocyte Colony-Stimulating Factor
  • Zidovudine