Hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders: studies of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and Flt-3 ligand (Flt3L)

The levels of hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders were investigated using a variety of a pproaches. Firstly, serum levels of granulocyte-macrophage colony-stimulati ng factor (GM-CSF), G-CSF and Flt3-ligand (Flt3L) were examined in acute le ukemia patients with treatment-induced cytopenia and complicating bacterial infections, Increased serum levels of both G-CSF and Flt3-ligand (Flt3L) w ere detected when these patients developed therapy-induced leukopenia, wher eas GM-CSF levels were low or undetectable, Development of complicating bac terial infections then increased the serum levels of both G- and GM-CSF, an d the Flt3L levels remained high during the infections. Secondly, release o f growth factors was characterized for clonogenic T cells that remained in the circulation of acute leukemia patients with chemotherapy-induced cytope nia, CD4(+) and CD8(+) T cells from these patients released high levels of GM-CSF, relatively low levels of IL-3 secretion having been detected, and o nly a minority of the clones released detectable amounts of Flt3L, Thus, ci rculating T cells may contribute to the high systemic growth factor levels in cytopenic patients, Thirdly, plasma levels of GM-CSF and interleukin-3 ( IL-3) were examined in patients with malignant disorders who received chemo therapy plus G-CSF for stem cell mobilization, Increased levels of GM-CSF a nd Flt3L were detected both in the patients' plasma and in the stem cell gr afts'. Despite the increased growth factor levels in neutropenic patients w ith complicating infections, the occurrence of febrile neutropenia did not have a major impact on normal hematopoietic reconstitution (i,e, duration o f treatment-induced neutropenia) after intensive chemotherapy for acute mye logenous leukemia.