Scientific basis and criticism of current therapy of acute leukemia

The factors which are thought to determine the response of acute leukemia (AL) to therapy are: 1) tumor size 2) drug dose 3) sensitivity to drug, 4) scheduling of drugs and 5) suppression of normal hemopoiesis. Each of these factors is considered in terms of the scientific data supporting their importance. Inability to measure the size of the tumor mass during all phases of treated AL continues to weaken rational strategies for therapy especially maintenance chemotherapy. Increasing the drug dose improves cell kill and potentially the cure rate up to the limits of toxicity. These limits may be extended by bone marrow transplantation. Various systems to study the drug sensitivity of leukemic cells are in experimental use, including stem cell assays but as yet they do not give a guide to altering therapy. The scheduling of multiple drugs is designed to increase cell kill by recruitment into the cycle, but "sanctuaries" appear to exist for resting cells. The suppression of normal hemopoiesis apparently due to leukemia-associated inhibitors is associated with favorable prognosis in childhood ALL but use of this information to improve treatment protocols is still unclear.