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

Abstract 

This is the third paper in a series which describes a new remission induction regimen for patients with ‘poor prognosis’ acute myelogenous leukemia (AML). Twenty-four patients were treated with two one day pulses of chemotherapy separated by 96 h. Each pulse consisted of two doses of cytarabine and a single dose of mitoxantrone. Amifostine was administered three times a week after the second pulse of chemotherapy until treatment outcome became known. The first paper described the outcome of treatment while the second described the relationship of treatment outcome to the pretherapy characteristics of the leukemia. This paper describes the changes in the leukemia cells which occur during remission induction therapy. While only a limited number of specimens were available for each post treatment study, the studies demonstrated a profound fall in blood counts, BM cellularity, and telomerase activity in leukemia cells after pulse #1 of treatment. This fall was usually accompanied by a coordinate rise in IL6, TNFα, and IL1β transcripts within the AML cells which survived chemotherapy. High levels of telomerase activity in the day 5 marrow was correlated with high levels of IL1β transcripts which in turn were associated with treatment failure ascribable to resistant disease.

Abbreviations:  MDS, myelodysplastic disease, MPD, myeloproliferative disease, up, unfavorable prognosis associated with cytogenetic abnormalities, ip/fp, intermediate and favorable prognosis associated with cytogenetic abnormalities, wt, wild type gene