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Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human
B U Mueller1, F Jacobsen, K M Butler
1Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892.
Insights
Granulocyte colony-stimulating factor (G-CSF) effectively treated zidovudine (AZT)-induced neutropenia in pediatric HIV patients. This allowed children to continue AZT therapy at therapeutic doses, improving treatment outcomes.
Area of Science:
- Pediatric Hematology
- Infectious Diseases
- Pharmacology
Background:
- Bone marrow suppression is a primary dose-limiting toxicity of zidovudine (AZT) in pediatric HIV patients.
- Neutropenia necessitates AZT dose reduction or discontinuation, potentially compromising treatment efficacy.
Purpose of the Study:
- To evaluate the efficacy and safety of subcutaneous granulocyte colony-stimulating factor (G-CSF) in pediatric patients experiencing neutropenia during AZT therapy.
- To determine if G-CSF can enable patients to tolerate therapeutic doses of AZT.
Main Methods:
- Nineteen pediatric patients with absolute neutrophil counts < 0.8 x 10(9)/L during AZT therapy received G-CSF via a sliding dosing schedule.
- G-CSF was administered to maintain absolute neutrophil counts between 1.5 and 5.0 x 10(9)/L.
- Patients were monitored for 2 to 12 months for hematologic parameters and tolerability.
Main Results:
- G-CSF significantly increased median leukocyte counts (2.0 to 4.14 x 10(9)/L) and absolute neutrophil counts (1.02 to 2.96 x 10(9)/L).
- 17 of 19 patients successfully tolerated therapeutic AZT doses (120-180 mg/m2 every 6 hours) with G-CSF support.
- G-CSF was generally well-tolerated, with mild thrombocytopenia observed in nine patients.
Conclusions:
- Subcutaneously administered G-CSF is an effective strategy to manage AZT-related neutropenia in pediatric HIV patients.
- G-CSF therapy facilitates the continuation of AZT at therapeutic doses, potentially improving antiretroviral treatment adherence and outcomes.
- G-CSF offers a viable option for patients experiencing dose-limiting neutropenia during AZT treatment.
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.