Phase I study of recombinant human granulocyte-macrophage colony-stimulating factor in patients with bone marrow failure and malignancy.
Twenty-five patients with malignancy and/or bone marrow failure were treated with recombinant human granulocyte macrophage colony-stimulating factor (rh GM-CSF) (specific activity 5 x 10(7) units/mg, purity greater than 95%) given by continuous intravenous infusion at various fixed dose levels (15-500 micrograms/m2/day), as part of a phase I study. Treatment was associated with marked increases in white blood cell counts (2-70 fold), consisting mainly of neutrophilic granulocytes. Significant increases were also observed in eosinophils, monocytes and lymphocytes. In addition six patients had multilineage responses characterized by increases in platelet counts (greater than 2 fold and greater than 100,000/mm3) and reticulocyte counts (greater than 2 fold). Three of these 6 patients did not require red cell or platelet transfusion for 17 to 37 weeks. Treatment also resulted in an increase in bone marrow cellularity and myeloid: erythroid cell ratio. The common side effects were constitutional symptoms and bone pain. These findings demonstrate that rh GM-CSF is well tolerated when given by continuous IV infusion and is a potent stimulator of hematopoiesis in vivo.
Vadhan-Raj
S
S
Department of Clinical Immunology, M.D. Anderson Hospital and Tumor Institute, Houston, Texas 77030.
Kellagher
M J
MJ
Keating
M
M
Walters
R
R
Gutterman
J U
JU
D001853:Bone Marrow / Q000473:pathology*; D003115:Colony-Stimulating Factors / Q000627:therapeutic use* / Q000633:toxicity; D004341:Drug Evaluation; D004906:Erythrocyte Count; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D009369:Neoplasms / Q000188:drug therapy*; D010976:Platelet Count; D011994:Recombinant Proteins / Q000627:therapeutic use* / Q000633:toxicity
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor