Multivariate analysis of prognostic factors in acute myeloid leukemia: value of clonogenic leukemic cell properties

The initial clinical and biological parameters, including clonogenic leukemic cell (CFU-L) assay, were reviewed for their prognostic significance in a cohort of 188 adult patients with newly diagnosed untreated acute myeloid leukemia (AML). Almost all patients received induction therapy with daunorubicin (DNR) and cytarabine (Ara-C) according to the European Organization for Research and Treatment of Cancer (EORTC) AML 5 to AML 9 trials. Bone marrow samples from 116 representative patients were obtained for CFU-L assay with an efficiency percentage of 89.6%; 76 patients had a measurement of the CFU-L self-renewal capacity (second plating efficiency [PE2]) and 91 patients had CFU-L inhibition test after exposure to DNR and/or Ara-C. The prognostic significance of parameters such as age, hematological antecedent, WBC count, liver enlargement, and Auer rods is confirmed in the present study. Moreover, high platelet and polymorphonuclear counts appeared to be related to resistance to induction course. However, through multivariate analysis, CFU-L sensitivity to drugs and self-renewal capacity appeared to be major independent prognostic factors in AML. A low CFU-L inhibition in the presence of the DNR and Ara-C combination correlates with a poorer complete remission (CR) rate, but not with CR duration. Patients with the lower PE2 values experienced both higher CR rate and longer CR duration. The practical interest of CFU-L study remains to be defined but, at least, PE2 measurement could be considered in the future as a major variable in determining therapeutic aggressiveness.