CYTOSINE-ARABINOSIDE AND MITOXANTRONE TREATMENT OF RELAPSED OR REFRACTORY CHILDHOOD LEUKEMIA - INITIAL RESPONSE AND RELATIONSHIP TO MULTIDRUG-RESISTANCE GENE-1

The objective of this study was to determine the response rate and tox icity of high-dose cytosine arabinoside (AC) and mitoxantrone (M) in r elapsed or refractory childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) and to correlate response with the express ion of the multidrug resistance gene 1 (mdr1). Twenty-nine patients we re treated with AC 1.0 g/m2 infused over 2 h every 12 h for eight dose s (days 1-4) and M 12 mg/m2 infused over 1 h (days 3-6). Mdr1 expressi on was determined by a polymerase chain reaction (pcr) assay. Ten of 1 5 patients (67%) with AML obtained a complete remission (CR) of 3 to 3 0+ months duration. Eight of 14 (57%) ALL patients obtained a CR of 1 to 23+ months duration. The major toxicities were hematopoietic and in fectious. Seventy-nine per cent of patients developed a documented inf ection during induction. Mdr1 did not correlate with a lower induction rate. This AC/M regimen is active in childhood AML and ALL. (C) 1994 Wiley-Liss, Inc.