Recombinant human granulocyte-macrophage colony-stimulating factor in septic neutropenic pediatric cancer patients: detection of circulating hematopoietic precursor cells correlates with rapid granulocyte recovery

Med Pediatr Oncol. 1995 Nov;25(5):365-71. doi: 10.1002/mpo.2950250502.

Abstract

Cycling intensive chemotherapy currently used to treat pediatric solid tumors induces severe neutropenia. Prolonged neutropenia is a major risk factor for septic death which occurs in up to 5% of febrile or septic neutropenic episodes. We treated 18 neutropenic pediatric cancer patients (eight females, 10 males) during 30 febrile and/or septic episodes with single daily doses of E. coli-derived non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rh-GM-CSF, 5 micrograms per kg of body weight). The cytokine was administered for a median period of 6.5 days (2-12 days). Analysis of circulating hematopoietic progenitor cells was performed at day 1 (baseline) and day 5 of rh-GM-CSF treatment and included flow cytometric CD34 analysis as well as the methylcellulose-based clonogenic assay. Prompt hematopoietic recovery and resolution of septic problems was observed in all children. The counts of leukocytes (WBC), absolute neutrophils (ANC), and platelets (PLT) rose above 1,000/microL, 1,000/microL, and 50,000/microL within 4 days (0-9), 5.5 days (2-13), and 6 days (0-14), respectively. Faster granulocyte recovery and improved recruitment of circulating hemopoietic precursors was observed in children with detectable amounts (> 0.1%) of CD34-positive mononuclear cells prior to rh-GM-CSF treatment. We conclude that, to some extent, the efficacy of rh-GM-CSF treatment in neutropenic cancer patients is influenced by the hematopoietic recovery status on the progenitor cell level. Although they respond more slowly to the treatment, patients without circulating CD34-positive progenitor cells may gain most from growth factor therapy. Rh-GM-CSF can be safely administered to febrile and/or septic neutropenic children treated for cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / analysis
  • Antigens, CD34
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Bacteremia / therapy*
  • Biomarkers, Tumor / analysis
  • Cell Count
  • Child
  • Child, Preschool
  • Colony-Forming Units Assay
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Granulocytes / pathology*
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Infant
  • Leukocyte Count
  • Male
  • Neoplasms / drug therapy*
  • Neutropenia / therapy*
  • Neutrophils / pathology
  • Platelet Count
  • Recombinant Proteins

Substances

  • Antigens, CD
  • Antigens, CD34
  • Biomarkers, Tumor
  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor