Therapy of Childhood Leukemia: Understanding Success and Failure

Abstract

The treatment of childhood acute lymphoblastic leukemia has revolutionized our concepts of what is possible in the management of all disseminated malignancy. From the cautious use of single—agent chemotherapy in the 1950s, therapy has evolved to include the aggressive use of multiple agents. The results have been a progressive increase in remission frequency and remission duration. However, the most important outcome has been the increased cure rate, which approximates 60% in many large studies. Progress has been slower in recent years, which has fostered the careful study of reasons for failure and the exploration of novel diagnostic, prognostic, and therapeutic techniques. We have been far less successful in acute myeloid leukemia, with cure rates of about 20%. We offer two examples of approaches to overcome the failures. We are studying pharmacodynamic variability because some failures may be due to ineffective dose-time exposure of leukemia cells; if so, more targeted dosage adjustment might improve results. Second, we are studying the application of growth factors in mitigating the negative effect of chemotherapy on normal marrow, as well as in influencing the growth of leukemia cells, particularly myeloid cells. We anticipate continued improvement in treatment outcome by empirical protocol modification, albeit at a slow rate, and potentially major improvements with help from the basic science laboratory.