title: Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors.
abstract: The biological mechanisms by which the association of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is expected to effectively reduce the hematological toxicity associated with chemotherapy (CT) are not completely elucidated. We exploited the cell kinetic changes of the bone marrow CD34(+) cell subset after CT followed by the IL-3+GM-CSF together with the clinical effects of this association. Eighteen patients with advanced cancers and normal hematopoiesis were treated with an intensified CT course (mg/m(2): CTX 1100, epirubicin 100, VP-16 200; iv day 1). Six cycles were planned at 14-day intervals with the support of IL-3 (5 mu g/kg/day; from day 2 to 6) sequenced with GM-CSF (same dose; from day 7 to 11). DNA content and bromodeoxyuridine incorporation were evaluated using flow cytometry on immunomagnetically-sorted bone marrow CD34(+) cells, at baseline and at different times (days 5, 6, 7, 8, 11 and 14) after CT followed by IL-3+GM-CSF. Treatment with IL-3 induced a marked increase in the % of myeloid precursors with respect to the baseline and in the % of CD34(+) cells in S-phase. However, while the first parameter remained elevated until day 14, the enhanced proliferative activity of the CD34(+) cell subset decreased after IL-3 was stopped and remained significantly low during GM-CSF administration. These data suggest a negative rebound effect on CD34(+) cell proliferation after IL-3 discontinuation which is maintained during GMCSF, that led to kinetic refractoriness of the hyperplastic marrow. In the 99 courses completed a rapid neutrophil and platelet recovery was obtained without cumulative multilineage toxicity. The modifications of CD34(+) cell cycling after CT followed by IL-3+GM-CSF could provide additional myeloprotection during multicyclic, dose-intensive programs.
authors.affiliation: IRCCS SAN MATTEO,I-27100 PAVIA,ITALY. CNR,STUDY CTR HISTOCHEM,I-27100 PAVIA,ITALY. UNIV PALERMO,HOSP P GIACCONE,I-90127 PALERMO,ITALY. SANDOZ SPA,ONCOHEMATOL DEPT,I-20135 MILAN,ITALY.
authors.forename: M
authors.initials: M
authors.lastname: Danova
authors.forename: G
authors.initials: G
authors.lastname: Mazzini
authors.forename: R
authors.initials: R
authors.lastname: Alberici
authors.forename: C
authors.initials: C
authors.lastname: Lucotti
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: G
authors.initials: G
authors.lastname: Fincato
authors.forename: M
authors.initials: M
authors.lastname: Cazzola
authors.forename: A
authors.initials: A
authors.lastname: Riccardi
authors.forename: E
authors.initials: E
authors.lastname: Ascari