Long-term results of the HEAVD protocol for adult acute lymphoblastic leukaemia

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 less than 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P less than 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)/l 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.