Chemotherapy of acute lymphocytic leukemia of childhood

A NEO-A plastic disease predominantly of childhood which in its untreated state leads swiftly to death.T h e manifestations of the disease in its florid state result from the defects in normal Iiematopoiesis with deficient production of granulocytes, tlwombocytes, antl erythrocytes.Normal lymphocytic function is also impaired.Although turneraction itself can lead to fatal outcome, particularly in the central nervous system, ordinarily death comes from infection or bleeding, atteiidiiiit upon the compromise in normal marrow function because of leukemic invasion or the ravages of treatment of atlvancetl disease.Dramatic alteration of leukemic mortality rate began alter 1948 with tlie first report OE an effective antimetabolite which produced selective toxicity against the tumor cells leading to temporary remission of the disease.5 'The discovery of other antimetabolites active ;against experimental leukemias of mice allowed the demonstration of the potential advantages of combination chemotherapy.l7Furthermore, the critical importance of dose scheduling and dose levels was c:lemonstrated.loSmall (young) tumors were found more responsive to drug treatment than large (old) tumors which contained more cells potentially resistant to the drug, and which liad destroyed more of the animal's normal i:issues and impaired its functions, thus plating i t closer to deatli.loIn the last 20 years, we have been involved in extrapolating these fundamental principles 1.0 clinical medicine and, from the design of similar experiments in man, have derived observations which themselves have become .