In vitro test for sensitivity of leukemic cells to L-asparaginase.

A method is proposed for measuring the cytocidal effect of L-asparaginase on leukemic blood cells as a possible means of screening patients for L-asparaginase therapy. On the average, L-asparaginase was more toxic to blood lymphocytes from patients with chronic lymphocytic leukemia than to lymphocytes from normal blood. A positive sensitivity test was defined as one in which 65% of lymphocytes were killed in 7 days by 0.17 i.u./ml of L-asparaginase. The sensitivity tests were positive in 25 tests on 37 leukemic patients; they were positive in none of the tests on 35 persons with normal hemograms. In 12 leukemic patients with negative sensitivity tests, the disease was in remission in three patients and was in an early stage in one case. Seventeen repeat tests within 5 weeks on 10 patients showed good reproducibility of results. L-Asparaginase was toxic to blood cells of three patients with acute lymphoblastic and myeloblastic leukemia but had relatively little toxicity to blood cells of five other patients with acute leukemia. Lymphocytes from chronic lymphocytic leukemia were usually sensitive to 0.17 i.u./ml, cells from two patients with acute lymphocytic leukemia were sensitive to 0.017 i.u./ml, and cells from the highly L-asparaginase-sensitive mouse lymphoma 6C3HED were sensitive to 0.0017 i.u./ml. In contrast, cells from the in vi'vo-resistant form of 6C3HED were resistant in vitro to 0.17