Related Experiment Videos
Recombinant human GM-CSF treatment of neutropenia in glycogen storage disease-1b
D Hurst1, L Kilpatrick, J Becker
1Division of Hematology/Oncology, Children's Hospital Oakland, California.
Insights
Recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) effectively increased neutrophil counts in patients with glycogen storage disease type 1b (GSD-1b). While beneficial for short-term infection treatment, local reactions may limit long-term use.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- Glycogen storage disease type 1b (GSD-1b) is characterized by chronic neutropenia and recurrent infections.
- Neutrophil dysfunction in GSD-1b impairs the immune response.
- Recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) is investigated for its potential to improve neutrophil counts.
Observation:
- Two patients with GSD-1b and chronic neutropenia received subcutaneous GM-CSF.
- Absolute neutrophil counts (ANC) significantly increased within 48 hours.
- Eosinophil counts also elevated; local reactions and febrile systemic reactions were noted with GM-CSF administration.
Findings:
- GM-CSF administration led to a rapid rise in absolute neutrophil counts.
- Despite no improvement in neutrophil superoxide anion generation, patients showed accelerated healing of cutaneous infections.
- Short-term GM-CSF treatment appears beneficial for serious infections in GSD-1b.
Implications:
- GM-CSF may be a valuable therapeutic option for short-term management of infections in GSD-1b.
- Further research into alternative dosing or formulations is needed for long-term GM-CSF therapy to mitigate adverse reactions.
- Granulocyte colony stimulating factor (G-CSF) is an alternative treatment option for GSD-1b that has not been associated with allergic reactions.
Purpose:
Recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) was administered to two patients with glycogen storage disease, type 1b (GSD-1b), with chronic neutropenia, neutrophil dysfunction, and recurrent infections in an effort to increase neutrophil counts and increase resistance to infections.
Patients And Methods:
The patients' baseline absolute neutrophil counts (ANC) ranged from 56 to 480 cells/mm3 despite increased granulocyte precursors in the bone marrow. GM-CSF was given s.c. at starting doses of 500 micrograms/m2/day divided into two doses.
Results:
After 48 h, ANC rose to 2,025 cells/mm3 and 3,132 cells/mm3, respectively. Absolute eosinophil counts also rose to 1,048 cells/mm3 (24%) and 4,820 cells/mm3 (33%) on days 10 and 9 in the two patients. Although an initial 10-day course of GM-CSF was tolerated in one patient without significant reactions, subsequent s.c. injections of GM-CSF were complicated by increasingly painful local reactions that necessitated discontinuation after 7 to 8 days. Intravenous infusion was associated with a febrile systemic reaction. Despite lack of improvement in neutrophil superoxide anion generation measured in one, both patients demonstrated unusually rapid healing of cutaneous infections on GM-CSF.
Conclusion:
Our experience suggests that GM-CSF may be useful for short-term treatment of serious infections in GSD-1b. However, alternate dosage schedules or different preparations of GM-CSF to diminish local reactions would be required for long-term maintenance therapy. Granulocyte colony stimulating factor (G-CSF) has also been shown to increase neutrophils in this disease and has not been associated with allergic reactions.