LONG-TERM RESULTS OF THE HEAVD PROTOCOL FOR ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA

Between 1979 and 1987, 82 adults (age 14-71 years) with acute lymphoblastic leukaemia (ALL) were treated with a 6-course protocol called HEAVD, the main feature of which was the early postremission administration of escalating doses of doxorubicin (total 405 mg/m2) and cyclophosphamide (total 2.5 g/m2). A complete remission (CR) was attained in 66 patients (80%, 95% confidence intervals, [CI] 71%-89%). Factors affecting favourable CR achievement were age < 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P < 0.05). Median duration of CR was 27 months. 26 patients remain in first continuous and unmaintained CR, 18 of whom between 5.9 and 11.1 years, for an estimated 39% prolonged disease-free survival (95% CI 27%-51%). CR duration correlated significantly with absolute blast cell count (15 x 10(9)/1 or less compared to more) and age (30 years or under compared to over). Overall, 29 patients are alive with a median follow-up of 6.7 years, the projected long term survival being 35% at 11 years (95% CI 24%-46%). Treatment-related toxicity included 1 lethal case of L-asparaginase-related thromboembolism and 3 toxic deaths among 66 CR patients. Late-onset toxicity was not observed in long-term survivors. The relatively late occurrence of endpoint events (relapse and death) in adult ALL confirms that long-term updating is necessary to determine the curative potential of modern chemotherapy programs for the disease.