Stimulation of hematopoiesis in patients with bone marrow failure and in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor

S. Vadhan-Raj, S. Buescher, A. LeMaistre, M. Keating, R. Walters, C. Ventura, W. Hittelman, Hal Broxmeyer, J. U. Gutterman

Research output: Contribution to journalArticle

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Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotential hematopoietin. To assess the toxicity and biological activity of recombinant human GM-CSF (rhGM-CSF) in vivo, 25 patients with malignancy or bone marrow failure were treated with rhGM-CSF (specific activity ~5 x 107 U/mg) as part of a phase I trial. The treatment was administered by continuous intravenous (IV) infusion daily for 2 weeks at fixed dose levels and repeated after a 2-week rest period. Over the entire dose range tested (15 to 500 μg/m2/d), rhGM-CSF treatment was associated with dramatic increases (two- to 70-fold) in total leukocyte counts, which consisted predominantly of neutrophils, bands, eosinophils, and monocytes. Furthermore, six of the 14 patients with one or more cytopenias that received at least two cycles of treatment had multilineage responses characterized by twofold or greater increases in platelet count to a level above 100,000, twofold or greater increases in corrected reticulocyte count, and a reduced requirement for red cell transfusions. Three of these patients became independent of both red cell and platelet transfusions for 17 to 37 weeks of follow-up. Treatment was associated also with an increase in bone marrow cellularity and frequency of cycling progenitor cells. The treatment was well tolerated; side effects included constitutional symptoms and bone pain. These results demonstrated that rhGM-CSF has a significant impact on hematopoiesis in patients with advanced malignancy and also in patients with bone marrow failure.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalBlood
Volume72
Issue number1
StatePublished - 1988
Externally publishedYes

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Hematopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Bone
Bone Marrow
Neoplasms
Platelets
Hematopoietic Cell Growth Factors
Cells
Reticulocyte Count
Therapeutics
Platelet Transfusion
Bioactivity
Platelet Count
Leukocyte Count
Eosinophils
Intravenous Infusions
Human Activities
Toxicity
Monocytes
Neutrophils

ASJC Scopus subject areas

  • Hematology

Cite this

Vadhan-Raj, S., Buescher, S., LeMaistre, A., Keating, M., Walters, R., Ventura, C., ... Gutterman, J. U. (1988). Stimulation of hematopoiesis in patients with bone marrow failure and in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor. Blood, 72(1), 134-141.

Stimulation of hematopoiesis in patients with bone marrow failure and in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor. / Vadhan-Raj, S.; Buescher, S.; LeMaistre, A.; Keating, M.; Walters, R.; Ventura, C.; Hittelman, W.; Broxmeyer, Hal; Gutterman, J. U.

In: Blood, Vol. 72, No. 1, 1988, p. 134-141.

Research output: Contribution to journalArticle

Vadhan-Raj, S, Buescher, S, LeMaistre, A, Keating, M, Walters, R, Ventura, C, Hittelman, W, Broxmeyer, H & Gutterman, JU 1988, 'Stimulation of hematopoiesis in patients with bone marrow failure and in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor', Blood, vol. 72, no. 1, pp. 134-141.
Vadhan-Raj, S. ; Buescher, S. ; LeMaistre, A. ; Keating, M. ; Walters, R. ; Ventura, C. ; Hittelman, W. ; Broxmeyer, Hal ; Gutterman, J. U. / Stimulation of hematopoiesis in patients with bone marrow failure and in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor. In: Blood. 1988 ; Vol. 72, No. 1. pp. 134-141.
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