RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INSEPTIC NEUTROPENIC PEDIATRIC CANCER-PATIENTS - DETECTION OF CIRCULATING HEMATOPOIETIC PRECURSOR CELLS CORRELATES WITH RAPID GRANULOCYTE RECOVERY

Cycling intensive chemotherapy currently used to treat pediatric solid tumors induces severe neutropenia. Prolonged neutropenia is a major r isk factor for septic death which occurs in up to 5% of febrile or sep tic neutropenic episodes. We treated 18 neutropenic pediatric cancer p atients (eight females, 10 males) during 30 febrile and/or septic epis odes with single daily doses of E. coli-derived non-glycosylated recom binant human granulocyte-macrophage colony-stimulating factor (rh-GM-C SF, 5 mu g per kg of body weight). The cytokine was administered for a median period of 6.5 days (2-12 days). Analysis of circulating hemato poietic progenitor cells was performed at day 1 (baseline) and day 5 o f rh-GM-CSF treatment and included flow cytometric CD34 analysis as we ll as the methylcellulose-based clonogenic assay. Prompt hematopoietic recovery and resolution of septic problems was observed in all childr en. The counts of leukocytes (WBC), absolute neutrophils (ANC), and pl atelets (PLT) rose above 1,000/mu L, 1,000/mu L, and 50,000/mu L withi n 4 days (0-9), 5.5 days (2-13), and 6 days (0-14), respectively. Fast er granulocyte recovery and improved recruitment of circulating hemopo ietic 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 reco very status on the progenitor cell level. Although they respond more s lowly to the treatment, patients without circulating CD34-positive pro genitor cells may gain most from growth factor therapy. Rh-GM-CSF can be safely administered to febrile and/or septic neutropenic children t reated for cancer. (C) 1995 Wiley-Liss, Inc.