“Total therapy” studies of acute lymphocytic leukemia in children. Current results and prospects for cure

Abstract

The ultimate goal of “total therapy” studies has been to establish a significant cure rate for childhood acute lymphocytic leukemia. The principle features of these studies have included administration of maximum tolerated combination chemotherapy and “prophylactic” central nervous system (CNS) irradiation. In the first three studies, a 17% 7-year leukemia-free remission rate was attained. The number of patients in complete remission decreased exponentially until 2 to 3 years, but stabilized thereafter. Complete remission duration was the earliest and most accurate indicator of long-term leukemia-free remission. In Study V, more aggressive CNS therapy was given and over half the patients have been in continuous complete remission for 3 1/2 to 4 years. Similar results are emerging in subsequent studies which also employ aggressive “prophylactic” CNS therapy. Therapy was stopped after 2 or more years of complete remission in 42 patients in “total therapy” studies, and nine have relapsed. Six of the nine had not received “prophylactic” CNS irradiation. If current trends in these studies continue, we can expect a 50% long-term leukemia-free remission rate. Thus, with currently available modalities of therapy, the prospects for cure appear bright.