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Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors

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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.
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Document Type: Research Article


Publication date: November 1, 1996

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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