Clinical results of treatment with E. coli L-asparaginase in adults with leukemia, lymphoma, and solid tumors.

Abstract

E. coli L-asparaginase (A-ase) was administered to 163 adults with different forms of leukemia, lymphoma, and solid tumors. Six of 11 patients with acute lymphoblastic leukemia and 4 of 32 patients with acute myeloblastic, myelomonoblastic, or undifferentiated leukemia had complete or good partial remissions. Doses of 10 to 5000 IU/kg/day were used, but there was no clear correlation between dose and therapeutic response, nor with any particular preparation of A-ase. Some of the others had transient physical and/or hematologic improvement, but remission was not achieved. Nineteen patients with myeloblastic leukemia, 4 with lymphoblastic and 3 with undifferentiated, had no response. Eight patients with acute leukemia (7 lymphoblastic and one myeloblastic), who were already in complete remission induced with other agents, were treated with 1000 IU/kg/day or higher doses of A-ase for one month or longer. Seven were given no further therapy. The disease relapsed within 2-5 months in 6 patients, but one is still in remission after 8 months. The eighth patient is still in remission after 3 months but is receiving other chemotherapy. Partial hematologic responses occurred in one patient with untreated chronic granulocytic leukemia, in 4 of 5 patients in a blastic phase of chronic granulocytic leukemia, and in 2 of 3 patients with chronic lymphocytic leukemia, but in none of these patients was the response of substantial clinical benefit. Two patients with disseminated lymphosarcoma or reticulum cell sarcoma had excellent therapeutic responses to A-ase, and 4 others showed some improvement while 14 had no detectable response. Eight patients with advanced Hodgkin's disease showed no response. One patient with malignant melanoma with multiple cutaneous metastases had temporary regression of his metastatic nodules with A-ase on several occasions, but evaluation of this case was complicated by other chemotherapy. Twenty-nine other patients with melanoma had no response nor did 45 patients with other types of solid tumors. Some toxic manifestations of A-ase occurred in almost all patients; these were generally more severe and sometimes were intolerable at higher dosage levels. The toxicity will be discussed in detail in an accompanying report.