SEVERE TOXICITY LIMITS INTENSIFICATION OF INDUCTION THERAPY FOR ACUTELYMPHOBLASTIC-LEUKEMIA

Fourteen adult patients with newly-diagnosed acute lymphoblastic, leuk emia (ALL), and lymphoblastic lymphoma, were treated with a dose-inten se induction regimen. This regimen was designed to increase the fracti on of patients achieving an early complete remission, in an attempt to increase the fraction of patients who are long-term disease-free surv ivors. The induction regimen included vincristine, prednisone, interme diate-dose cytarabine (Ara-C), and idarubicin, all given during the fi rst week of therapy. This combination led to significant hepatic, gast rointestinal, infectious, and neurologic toxicity. There was unaccepta ble 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 nin e complete remissions, three early deaths, and two patients with resis tant disease. There have been six relapses, three of which occurred in patients who, because of protracted grade III/IV toxicity, were no lo nger receiving chemotherapy. With a minimum follow-up of 20 months, on ly three patients are still alive. We conclude that this combination o f vincristine, prednisone, Ara-C, and idarubicin, is too toxic to be u sed as induction therapy for adult patients with ALL and lymphoblastic lymphoma.