PMID: 7522289Sep 1, 1994Paper

Hematopoietic growth factor stimulation and cytarabine cytotoxicity in vitro: effects in untreated and relapsed or primary refractory acute myeloid leukemia cells

Leukemia
P A te BoekhorstP Sonneveld

Abstract

Stimulation of clonogenic acute myeloid leukemia (AML) cells by hematopoietic growth factors (HGF) is capable of enhancing cytosine-arabinoside (Ara-C) cytotoxicity in vitro. Until now it has not been known to what extent in vitro Ara-C cytotoxicity can be restored by HGF stimulation in samples from previously treated AML patients. Therefore, we studied the individual effects of the hematopoietic growth factors (HGF) granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation on the Ara-C sensitivity of clonogenic leukemic cells from six patients with newly diagnosed AML. These results were directly compared with the outcome using AML samples from the same patients at relapse or primary refractory AML. In one patient, a sample of the second relapse was also studied. The results were expressed as IC50 values, and were used to calculate sensitivity ratios, defined as the ratio of the IC50 value with drug exposure alone and with HGF plus Ara-C. In AML samples treated with Ara-C alone and no HGF, IC50 values of Ara-C in relapsed/refractory AML were greater than IC50 values of AML cells at diagnosis. Addition of either HGF enhanced the Ara-C cytotoxic...Continue Reading

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