TY - JOUR AB - 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. AD - 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. AU - Danova,M AU - Mazzini,G AU - Alberici,R AU - Lucotti,C AU - Palmeri,S AU - Fincato,G AU - Cazzola,M AU - Riccardi,A AU - Ascari,E DA - 1996/11/01 DO - 10.3892/ijo.9.5.971 EP - 976 IS - 5 JO - Int J Oncol PY - 1996 SN - 1019-6439 1791-2423 SP - 971 ST - Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors T2 - International Journal of Oncology TI - Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors UR - https://doi.org/10.3892/ijo.9.5.971 VL - 9 ER -