TREATMENT OF ACUTE MYELOID-LEUKEMIA AND MYELODYSPLASTIC SYNDROME BY LOW-DOSE ARABINOSYL CYTOSINE

Twenty-six patients with subacute or acute myeloid leukemia (sAML, AML) or with a myelodysplastic syndrome (age range 42-85 years, median 68) were treated with one or more courses of low dose Arabinosyl Cytosine (ARA-C): 15 to 20 mg/m2/day i.v. or i.m. q 12 or 48 h for 8 to 20 days. One patient with de novo AML achieved complete remission. A partial remission, with a significant improvement in blood counts, was obtained in 6 patients (23%) (0/2 cases of refractory anemia (RA), 1/5 cases of RA with excess of marrow blasts, 1/2 cases of chronic myelomonocytic leukemia, 2/7 cases of sAML, and 2/10 cases of AML). Remissions were obtained after 1 course (3 cases) or 2 courses (4 cases) of low dose ARA-C and lasted 2 to 5 months. Severe marrow hypoplasia developed in 11 of 26 cases (42%). Severe granulocytopenia (< 1 .times. 109/l) and thrombocytopenia (< 50 .times. 109/l) were induced in 35% and 50% of the cases, respectively. Comparison with prior reports points to a great variability of treatment results, so that it is not yet possible to assess with accuracy the efficiency of low dose ARA-C, either as regards its anti-leukemic effect or its myelotoxicity. We suggest that the main mechanism of action of low dose ARA-C rests on inhibition of cell proliferation, as with standard ARA-C regimes, and that enhancement of cell maturation may be a secondary effect.