Effect of rhGM-CSF on the Kinetics of Hematopoiesis in Long-term Marrow Cultures from Patients with Acute Myelogenous Leukemia

Abstract

In the present study, we have assessed the effects of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) in Dexter-type long-term marrow cultures (LTMC) from patients with acute myelogenous leukemia (AML). Addition of rhGM-CSF to AML LTMC resulted in a significant increase in the number of total nucleated cells (1.3-4.3-fold, as compared to untreated cultures). However, a simultaneous decrease in the numbers of myeloid progenitor cells (CFU) was observed. Interestingly, there was a selective stimulation of the growth of leukemic progenitors (AML-CFU). Indeed, whereas on day 0 these cells were detected in only 2 patients, between weeks 1 and 5 they were detected in 10 of the 14 patients included in the study. It is noteworthy that around 50% of the cells detected in the non-adherent fraction of rhGM-CSF-treated AML LTMC were blasts, whereas in untreated cultures, blasts corresponded to only 23% of the non-adherent cells, and the majority corresponded to cells of the monocyte-macrophage lineage. These results indicate that rhGM-CSF is a cytokine with a significant stimulatory activity for the in vitro growth of AML progenitor and blast cells, and, together with previous reports in the literature, suggest that the use of rhGM-CSF in clinical settings must be taken with caution since this cytokine, although beneficial in reducing the risk of infections after chemotherapy, may induce the reappearance of the disease after treatment. Further studies should be encouraged to understand in greater detail the effects of rhGM-CSF, and other cytokines, on the hematopoietic system of AML patients.