Acute Myeloid Leukemias Differ at Primary Diagnosis and Relapse in Endogenous Proliferative Activity, Response to Stimulation by Exogenous G-CSF and GM-CSF and Production of G-CSF

The endogenous proliferative activity (EPA) of leukemic blasts was shown to be associated with cytogenetically defined prognostic subgroups of AML in previous studies. Especially blasts with inv(16) or t(8;21) had a significantly higher EPA than prognostically unfavourable alterations, which was associated with a higher degree of incorporation of AraCTP — the active moiety of AraC — into the DNA — suggesting a pharmacodynamic basis for the increased efficacy of AraC based treatment regimens in these subtypes. In the present study parameters of cell proliferation were investigated in AML at primary diagnosis and at relapse to substantiate the hypothesis that cytokinetic factors might underlie the substantially inferior efficacy of S-phase specific agent based regimens at AML relapse. The EPA of AML blasts at primary diagnosis (n=43) and at relapse (n=15) were determined by 3H Thymidine uptake. To specify proliferative biology we also measured possibilities of stimulation and production of cytokines.