Synergistic and antagonistic effects of myeloid growth factors on in vitro cellular killing by cytotoxic drugs.
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.
Nørgaard
J M
JM
University Department of Medicine, Aarhus University Hospital, Denmark.
Langkjer
S T
ST
Ellegaard
J
J
Palshof
T
T
Clausen
N
N
Hokland
P
P
D015250:Aclarubicin / Q000008:administration & dosage / Q000633:toxicity; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004396:Coloring Agents; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003630:Daunorubicin / Q000633:toxicity; D004336:Drug Antagonism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000633:toxicity*; D006801:Humans; D007377:Interleukin-3 / Q000633:toxicity*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction
D000970:Antineoplastic Agents; D004396:Coloring Agents; D007377:Interleukin-3; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D015250:Aclarubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003630:Daunorubicin