title: Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia.
abstract: Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte-macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.
authors.affiliation: Preclinical and Clinical Research, Sandoz, Ltd, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Nissen
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
authors.forename: B
authors.initials: B
authors.lastname: Speck
authors.forename: A
authors.initials: A
authors.lastname: Milne
authors.forename: E C
authors.initials: EC
authors.lastname: Gordon-Smith
authors.forename: J
authors.initials: J
authors.lastname: Schaedelin
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000150:complications / Q000188:drug therapy*; D002648:Child; D003115:Colony-Stimulating Factors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006098:Granulocytes; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008264:Macrophages; D008297:Male; D009503:Neutropenia / Q000209:etiology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins