Poor prognosis acute myelogenous leukemia: 3-biological and molecular biological changes during remission induction therapy

This is the third paper in a series which describes a new remission inducti on regimen for patients with 'poor prognosis acute myelogenous leukemia (AM L). Twenty-four patients were treated with two one day pulses of chemothera py separated by 96 h. Each pulse consisted of two doses of cytarabine and a single dose of mitoxantrone. Amifostine was administered three times a wee k after the second pulse of chemotherapy until treatment outcome became kno wn. The first paper described the outcome of treatment while the second des cribed the relationship of treatment outcome to the pretherapy characterist ics of the leukemia. This paper describes the changes in the leukemia cells which occur during remission induction therapy. While only a limited numbe r of specimens were available for each post treatment study, the studies de monstrated a profound fall in blood counts, BM cellularity, and telomerase activity in leukemia cells after pulse # I of treatment. This fall was usua lly accompanied by a coordinate rise in IL6, TNF alpha. and IL1 beta transc ripts within the AML cells which survived chemotherapy. High levels of telo merase activity in the day 5 marrow was correlated with high levels of IL1 beta transcripts which in turn were associated with treatment failure ascri bable to resistant disease. (C) 2001 Elsevier Science Ltd. All rights reser ved.