Synergistic and antagonistic effects of myeloid growth factors on in vitro cellular killing by cytotoxic drugs

• Published in: Leukemia research Vol. 17; no. 8; pp. 689 - 694
• Main Authors: Nørgaard, Jan M., Langkjer, Sven T., Ellegaard, Jørgen, Palshof, Torben, Clausen, Niels, Hokland, Peter
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1993; Elsevier Science
• Subjects: Aclarubicin - administration & dosage; Aclarubicin - toxicity; Acute Disease; Adult; Aged; Aged, 80 and over; AML; Antineoplastic agents; Antineoplastic Agents - toxicity; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Ara-C; Biological and medical sciences; Cell Death - drug effects; Cell Survival - drug effects; Coloring Agents; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Cytarabine - administration & dosage; Cytarabine - therapeutic use; Cytarabine - toxicity; daunorubicin; Daunorubicin - toxicity; Drug Antagonism; Drug Screening Assays, Antitumor - methods; Drug Synergism; Female; Granulocyte Colony-Stimulating Factor - toxicity; Granulocyte-Macrophage Colony-Stimulating Factor - toxicity; growth factors; Humans; Interleukin-3 - toxicity; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - pathology; Male; Medical sciences; Middle Aged; MTT assay; Pharmacology. Drug treatments; Prospective Studies; Remission Induction; resistance modulation; AML; hrGM-CSF; hrIL-3; growth factors; Acla; hrG-CSF; Dau; resistance modulation; MTT assay; Ara-C; daunorubicin; Mitox; Antineoplastic agent; Drug combination; Acute; Cytokine; Cytotoxicity; Malignant hemopathy; In vitro; Antibiotic; Granulocyte colony stimulating factor; Interleukin 3; Anthracyclins; Drug interaction; Pyrimidine nucleoside; Negative therapeutic reaction; Granulocyte macrophage colony stimulating factor; Acute myelocytic leukemia
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(93)90075-V

The effect of stimulating acute myeloid leukemia blast cells with a combination of growth factors (G-CSF, GM-CSF, and IL-3) on cellular resistance to the antileukemia drugs Ara-C, daunorubicin, aclarubicin, and mitoxantrone was studied. For assessment of in vitro cellular drug resistance the MTT assay was employed. Stimulated cells showed enhanced sensitivity to Ara-C ( p < 0.02), whereas a significant increase in cellular drug resistance to daunorubicin ( p < 0.02) was observed. Variable and statistically non-significant changes in drug resistance to aclarubicin and mitoxantrone was induced by stimulation of the blast cells. We conclude on the basis of these observations that myeloid growth factors should be used with caution in combination with daunorubicin in AML treatment until further confirmatory evidence has been presented by other investigators.