title: GM-CSF safety and effects in the management of advanced/refractory multiple myeloma patients: a phase I trial.
abstract: OBJECTIVE
  Some limitations of effective therapy in multiple myeloma include the low growth fraction of the malignant plasma cells, multi-drug resistance, and the presence of other concurrent diseases in this patient population. A phase I study was conducted to evaluate the toxicity of granulocyte macrophage colony stimulating factor (GM-CSF) in myeloma patients as well as the potential effect on the plasma cell labeling index (PCLI). Relapsed patients with multiple myeloma were eligible.
  
  
  METHODS
  The first phase of this trial assessed the toxicity (including the effect on disease progression) of escalating doses (125-500 microg/m2 SC, days 1-5) of GM-CSF, and the effects of this cytokine on PCLI. Patients whose PCLI doubled and increased to > or = 1.7% were treated with chemotherapy including cyclophosphamide, vincristine, prednisone, and GM-CSF. Twenty-two patients were enrolled.
  
  
  RESULTS
  The toxicity of GM-CSF was mild, and no dose-limiting side effects were seen. Twenty-five percent of patients (5/20) achieved the target PCLI, and 4/5 proceeded to receive chemotherapy. No relationship of GM-CSF dose to increases of the PCLI was noted. All patients who received chemotherapy responded.
  
  
  CONCLUSIONS
  GM-CSF has acceptable toxicity in patients with multiple myeloma and produced increases of PCLI in selected individuals. Further studies of GM-CSF alone or in combination with chemotherapy are indicated.
authors.affiliation: The Cleveland Clinic Foundation, Multiple Myeloma Program, Cleveland Clinic Taussig Cancer Center, OH 44195, USA. husseim@ccf.org
authors.forename: M A
authors.initials: MA
authors.lastname: Hussein
authors.forename: K
authors.initials: K
authors.lastname: Sandstrom
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.forename: J
authors.initials: J
authors.lastname: Finke
authors.forename: D
authors.initials: D
authors.lastname: McLain
authors.forename: P
authors.initials: P
authors.lastname: Rayman
authors.forename: L A
authors.initials: LA
authors.lastname: Rybicki
authors.forename: R A
authors.initials: RA
authors.lastname: Bukowski
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects*; D006801:Humans; D007275:Injections, Intravenous / Q000009:adverse effects*; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D018579:Patient Selection; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase