Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation

Blood. 1991 May 1;77(9):2065-71.

Abstract

Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow Transplantation*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cyclosporins / therapeutic use
  • Drug Evaluation
  • Female
  • Fever / prevention & control
  • Graft vs Host Disease / prevention & control
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Hodgkin Disease / therapy
  • Humans
  • Infection Control
  • Leukemia / therapy*
  • Lymphoma / therapy*
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Prednisone / therapeutic use
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use

Substances

  • Cyclosporins
  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Prednisone
  • Methotrexate