Treatment of acute myeloid leukemia and blastic phase of chronic myeloid leukemia with combined eflornithine (alpha difluoromethylornithine) and methylglyoxal-bis-guanyl hydrazone (methyl-GAG).

Abstract

A combined eflornithine-MGBG treatment was studied in patients with acute myeloid leukemia (AML) or blastic transformation of chronic myeloid leukemia (BT CML). The first ten patients (5 AML, 5 BT CML) received i.v. or p.o. eflornithine 6 g m-2 day-1 and i.v. MGBG 500 mg/m2 once a week. The duration of treatment was 5-37 days (median 15) with one to five MGBG infusions (median 2). The results were complete response (CR) in one patient, partial response (PR) in four, minimal response (MR) in one and failure (F) in four. Pronounced side effects, including severe mucositis, gastrointestinal disturbances and skin infiltration, were observed in eight patients. As the four PRs were achieved in patients with BT CML, it was decided also to study ten patients with this indication. In attempts to decrease the incidence and severity of unwanted effects, lower doses of eflornithine-MGBG were used, i.e., eflornithine 4 g m-2 day-1 and MGBG 200 mg m-2 once a week. The duration of treatment was 9-110 days (median 46), with 2-14 MGBG infusions (median 6). Responses observed were CR in two patients (in one of whom it was only transient), transient PR in two, transient MR in four, and F in two. Treatment at lower doses was better tolerated, thus allowing a longer duration of treatment. Five of ten patients had moderate or severe gastrointestinal disturbances and one patient had a severe subjective hearing loss. The eflornithine-MGBG combination may prove to be a useful alternative treatment for AML and BT CML, but comparative trials will ultimately be necessary for a more definitive assessment of the combination.