Treatment of Poor Risk Acute Leukemia With Sequential High-Dose ARA-C and Asparaginase

• Published in: Blood 1984-03, Vol.63 (3), p.694-700
• Main Authors: Capizzi, Robert L., Poole, Michael, Cooper, M. Robert, II, Fred Richards, Stuart, John J., V. Jackson, Jr, Don, White, Douglas R., Spurr, Charles L., Hopkins, Judith O., Muss, Hyman B., Rudnick, Seth A., Wells, Robert, Gabriel, Don, Ross, Dennis
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase - administration & dosage; Asparaginase - adverse effects; Biological and medical sciences; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - pathology; Chemotherapy; Child; Cytarabine - administration & dosage; Cytarabine - adverse effects; Drug Resistance; Female; Humans; Leukemia - blood; Leukemia - drug therapy; Leukemia - pathology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V63.3.694.694

Resistance of leukemia cells to cytosine arabinoside (ARA-C) may be due to any one or combination of biochemical processes, which in certain instances may be substantially reversed by an appropriate increase in ARA-C dosage. Based on these and other laboratory observations indicating pharmacologic synergy between sequential high-dose ARA-C and asparaginase (HiDAC→ASNase), a therapeutic program was developed for the treatment of patients with acute nonlymphocytic leukemia (ANLL) refractory to conventional doses of ARA-C, as well as patients with high risk ANLL and advanced acute lymphocytic leukemia (ALL). Treatment consisted of 3-hr intravenous infusions of 3 g/sq m of ARA-C given at 12-hr intervals for 4 doses, followed by 6,000 IU/sq m ASNase given i.m. at hour 42. The same schedule was repeated on day 8. In 32 induction attempts, only 4 patients proved to be truly refractory, i.e., failed to achieve substantial leukemia cell cytoreduction. Complete remissions were achieved with HiDAC→ ASNase in 9 of 13 patients with refractory ANLL, 6 of 9 patients with antecedent hematologic disorders, and 3 of 10 patients with advanced ALL. These include 9 of 14 patients who had either failed induction or who had relapsed on active ARA-C therapy and 6 of 8 patients who had had no prior exposure to ARA-C. The median duration of unmaintained remission in ANLL was 5 mo. In a patient with central nervous system (CNS) leukemia, there was clearance of cerebral spinal fluid (CSF) blasts without intrathecal therapy, suggesting a role for HiDAC in CNS prophylaxis. In general, toxicity was tolerable and reversible. These data suggest that HiDAC→ASNase is an exceptionally effective and well tolerated regimen in leukemic patients with antecedent hematologic disorders and in those refractory to conventional doses of ARA-C.