Severe toxicity limits intensification of induction therapy for acute lymphoblastic leukemia

Fourteen adult patients with newly-diagnosed acute lymphoblastic, leukemia (ALL), and lymphoblastic lymphoma, were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission, in an attempt to increase the fraction of patients who are long-term disease-free survivors. The induction regimen included vincristine, prednisone, intermediate-dose cytarabine (Ara-C), and idarubicin, all given during the first week of therapy. This combination led to significant hepatic, gastro-intestinal, infectious, and neurologic toxicity. There was unacceptable treatment-related mortality (29%). After the first eight patients, the study was modified, omitting the Ara-C from the induction phase. Gastrointestinal morbidity was less in the cohort treated without Ara-C; however, infectious morbidity persisted at unacceptable levels and this program was terminated as too toxic to administer. There were nine complete remissions, three early deaths, and two patients with resistant disease. There have been six relapses, three of which occurred in patients who, because of protracted grade III/IV toxicity, were no longer receiving chemotherapy. With a minimum follow-up of 20 months, only three patients are still alive. We conclude that this combination of vincristine, prednisone, Ara-C, and idarubicin, is too toxic to be used as induction therapy for adult patients with ALL and lymphoblastic lymphoma.