Correspondence

Low-Dose Filgrastim Therapy for Chronic Neutropenia

N Engl J Med 1993; 329:1280-1281October 21, 1993

Article

To the Editor:

Filgrastim (recombinant human granulocyte colony-stimulating factor) is available for the treatment of chemotherapy-induced neutropenia. It is currently being investigated for use in bone marrow transplantation, aplastic anemia, myelodysplastic syndrome, and other chronic neutropenic states. The currently recommended doses of 120 to 350 μg per square meter of body-surface area are based on data on the treatment of chemotherapy-induced neutropenia, which is aimed at inducing proliferation of progenitor cells that have been depleted1-3. Many chronic neutropenic states, however, are characterized by ineffective hematopoiesis. In this situation, there is peripheral-blood cytopenia although the bone marrow is normocellular or hypercellular. In some of these diseases, such as the myelodysplastic syndrome, the obstacle to differentiation of blood cells can be overcome by therapy with hematopoietic growth factor in conventional doses4.

Low doses of granulocyte-macrophage colony-stimulating factor are effective in the treatment of chronic neutropenia related to myelodysplastic syndrome, human immunodeficiency virus (HIV) infection, and idiopathic neutropenia5. We report the use of low-dose filgrastim therapy in five patients with neutropenia related to myelodysplastic syndrome, one with multiple myeloma, one with HIV infection, and one with Shwachman's syndrome. The drug was first given in a dose of 5 μg per square meter per day by subcutaneous injection. The dose was increased to 10, 15, or 30 μg per square meter to achieve a neutrophil count above 1500 per cubic millimeter (Table 1Table 1Effect of Filgrastim on Neutrophil Counts of Patients with Chronic Neutropenia.). The patients have been treated for a median of 7 weeks (range, 2 to 38), with no loss of response. No noteworthy toxicity has been associated with treatment.

It is possible that substantial protection against prolonged neutropenia may result from the use of filgrastim in doses markedly lower than those currently recommended. The use of lower doses would reduce the cost of treatment. The annual cost of treatment per patient in the United Kingdom is over 29,000 pounds ($45,000) (a figure based on the currently recommended once-only use of a 300-μg vial costing 80 pounds [$125], at a dose of 150 μg per square meter per day). This has meant that treatment is inaccessible to many patients who may benefit from therapy with hematopoietic growth factor. With low-dose treatment, the annual cost could be reduced to 3,500 pounds ($5,400) (a figure based on multiple uses of a 300-μg vial, at a dose of 20 μg per square meter per day). Such savings could be realized only with multiuse vials or smaller, single-dose vials, since at present filgrastim (Neupogen, Amgen, Thousand Oaks, Calif.) is available in 300-μg vials to be used once only. Randomized trials are required to determine the efficacy of low-dose filgrastim therapy in reducing the incidence and severity of infections in patients with chronic neutropenia.

Richard S. Kaczmarski, M.R.C.P.
Ghulam J. Mufti, M.R.C.Path.
King's College School of Medicine and Dentistry, London SE5 9PJ, United Kingdom

5 References

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   Kaczmarski RS, Pozniak A, Lakhani A, Harvey E, Mufti GJ. A pilot study of low-dose recombinant human granulocyte-macrophage colony-stimulating factor in chronic neutropenia. Br J Haematol 1993;84:338-340
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