Current therapy for acute lymphocytic leukemia: is it rational?

It can be concluded that the therapy for acute lymphocytic leukemia has indeed been developed in a rational manner. Within the three decades of therapy evolution, evidence has accumulated that for some children with this disease cure is now a realistic goal. Two major areas of concern remain. As an increasing number of children achieve long-term disease-free survival, late consequences of the disease and its therapy have emerged as a serious consideration in the design of new treatment programs. Of these late consequences, the impaired intellectual performance found in some children, presumably related to CNS prophylaxis, is a particularly important concern. Current and future therapy protocols must address the problem of effective control of CNS leukemia with minimal consequences for normal brain function. The major deterrent to effective disease control at this time is bone marrow relapse. In some patients, drug-resistant leukemic cells, either preexistent at the time of diagnosis or acquired by modulation during drug exposure, develop a growth advantage and cause a return of the disease manifestation. Once relapse has occurred, expectations for subsequent cure are minimal. During the past decade, several clinical and biological features of acute lymphocytic leukemia have allowed for an increasingly accurate prediction of the risk for bone marrow relapse. Future studies must focus on therapeutic strategies designed to take into account the individual patient's risk of relapse. Further biological studies must focus on mechanisms of the acquisition of drug resistance and its prevention.