594 HIGH RISK ACUTE LYMPHOCYTIC LEUKEMIA (ALL): PROBLEM OF EARLY RELAPSE

Abstract

Over the past two decades there has been an increase in the proportion of children with ALL achieving long-term disease-free survival. An exception is found in patients now being identified as having high risk features (HRF). To determine if a cause for their treatment failure could be recognized, all children with ALL entered on “Total Therapy” Studies I-IX were analyzed. The relationship of 5 initial features and outcome of therapy was determined in 802 untreated children with ALL treated here from 1962-1977. The initial features chosen for analysis were: Mediastinal mass, leukocyte count above 100,000/mm3, age under 2 years, early CNS disease and black race. One or more HRF were present in 261 (33%) of the patients. Complete remission (CR) was achieved by 224 (86%) of patients with HRF and by 516 (95%) of patients without these features. The median duration of CR was 9 months in patients with HRF in contrast to 36+ months for all other patients. Regardless of the therapeutic changes made in Studies I-IX, the proportion of HRF patients remaining in complete remission from each study is consistently 20% or less. We conclude that most patients with HRF achieve CR and that the most important reason for poor prognosis is the short duration of CR. At least 80% eventually relapse. This observation suggests that (1) the leukemic cells in these patients develop resistance to therapy rapidly; and (2) the emergence of resistant cells should be prevented by modifying maintenance chemotherapy.