title: Recombinant human granulocyte-macrophage colony-stimulating factor in septic neutropenic pediatric cancer patients: detection of circulating hematopoietic precursor cells correlates with rapid granulocyte recovery.
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.
authors.affiliation: Department of Pediatrics, University of Innsbruck, Austria.
authors.forename: F M
authors.initials: FM
authors.lastname: Fink
authors.forename: K
authors.initials: K
authors.lastname: Maurer-Dengg
authors.forename: G
authors.initials: G
authors.lastname: Fritsch
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Zoubek
authors.forename: M
authors.initials: M
authors.lastname: Falk
authors.forename: H
authors.initials: H
authors.lastname: Gadner
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016470:Bacteremia / Q000628:therapy*; D014408:Biomarkers, Tumor / Q000032:analysis; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006098:Granulocytes / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000628:therapy*; D009504:Neutrophils / Q000473:pathology; D010976:Platelet Count; D011994:Recombinant Proteins
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor