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Potential clinical applications of rhGM-CSF in acute myeloid leukemia based on its biologic activity and receptor
F Lanza1, G M Rigolin, B Castagnari
1Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Italy.
Background And Objective:
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multilineage hemopoietic growth factor that stimulates proliferation, differentiation, and survival of progenitor cells, enhances the functional activities of mature myeloid effector cells, and plays a key role in host defense and the inflammatory process. Although the clinical use of rhGM-CSF in patients affected by lymphoid malignancies is widely accepted, its utility and safety in the management of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is still controversial. The three main schedules adopted for clinical application of GM-CSF in AML are as follows: A) post-chemotherapy, in order to shorten the duration of neutropenia and/or monocytopenia; B) prechemotherapy to recruit blast cells into active cell cycle phases, and to increase their sensitivity to cell cycle-dependent cytotoxic drugs; C) as a mobilizing agent to induce the release of progenitor cells from bone marrow into circulation (peripheral blood progenitor cell transplantation-PBPC). The objective of this paper is to analyze the potential clinical applications of rhGM-CSF in AML.
Evidence And Information Sources:
The material examined in the present review includes several personal papers in this field and articles and abstracts published in journals covered by the Science Citation Index.
State Of The Art:
Based on current knowledge, it may be argued that rhGM-CSF should be used only in a subset of AML patients at high risk of infection mortality, including elderly subjects, and/or in those AML patients who relapse or are resistant to induction treatment. However, the risk of stimulating the leukemic clone following GM-CSF therapy should be kept in mind when using this growth factor in the clinical setting, even though the great majority of the reported papers on this subject have shown that GM-CSF therapy does not affect relapse rates, frequency of remissions or patient life expectancy.
Perspectives:
It is likely that new data from controlled clinical trials will clarify the therapeutic role of GM-CSF in myeloid-derived malignancies, allowing the establishment of consensus guidelines for its use.