L-Asparaginase Therapy in Chemotherapy-Resistant Acute Lymphocytic Leukemias

Abstract

Effectiveness of L-asparaginase as an induction therapy was investigated in 12 patients of acute lymphocytic leukemia and one of peroxidase-negative acute myelocytic leukemia, refractory to conventional chemotherapy. The median age was 26 years (from 10 to 54 years). L-asparaginase was always tried after the multi-combination chemotherapy had proved unsuccessful, either during the initial phase of the disease or during relapse. In all cases except for two who were administered 20 I. U./Kg/day and 132 I. U./Kg/day, the dosis was approximately 200 I. U./Kg/day. The median duration of treatment was 14 days (from 3 to 22 days). Before L-asparaginase treatment, there was a heavy leukemic infiltration (53.2% median) of the bone marrow. The blood showed leukopenia and thrombocytopenia in several patients. Complete remission was obtained in 8 (61.2%) out of 13 cases of acute leukemia. The median remission induction time was 26 days. These 8 cases achieved complete remission within 30 days from the start of L-asparaginase treatment. No correlation of duration of remission induction with dose administered was found. With respect to a correlation between the time needed for remission with L-asparaginase and the duration of this remission, it is too early to mention because 4 out of 8 remission cases are still in complete remission. Clinically, L-asparaginase was well tolerated except for one case, where gastrointestinal complaints and hyperglycemia made it necessary to discontinue treatment after only 3 days. The other one patient developed an anaphylactic reaction which appeared during an attempt to restart the second treatment with L-asparaginase after a resting period General side effects were quite frequent. 92.3% of the cases experienced nausea and anorexia, 23.1% vomiting. An effect on the liver was frequently seen (53.8%). They disappeared quickly or returned normal after the end of the asparaginase course.
These results seem highly significant, in so far as L-asparaginase was applied for the patient who had previously proved to be refractory to the conventional chemotherapy.