Acute Lymphoblastic Leukemia: An Historical Perspective

Astute observations, dedicated researchers, cooperative groups, and clinical trials as well as guinea pig serum, hypoglycemic cows, and periwinkle plant extracts-all contributed to the evolution of the term "cure" used with acute lymphoblastic leukemia (ALL), a disease that was invariably fatal until the 1960s. Over 50 years ago methotrexate, asparaginase (discovered when guinea pig serum inhibited experimental lymphomas by degrading the essential amino acid asparagine to aspartic acid), 6 mercaptopurine (the first designer drug) and steroids were being used to treat children with ALL. Remissions were short lived and children died, generally within a year. Since many patients were needed to study these agents, ALL was the stimulus for the formation of modern cancer cooperative study groups. In the mid 1950s, three children's cooperative groups-Acute Leukemia Group A (eventually Children's Cancer Group CCG), Acute Leukemia Group B (which became Cancer and Leukemia Group B CALGB), and the Southwest Cancer Chemotherapy Study Group (which evolved into the Southwest Oncology Group SWOG)-formed in rapid succession. Internists also soon joined and began to enter patients into clinical trials. The 1960s were characterized by the discovery of vincristine, an extract from the periwinkle plant, which was being studied as a possible antiglycemic agent for hypoglycemic cows. It was noted to have a myelosuppressive effect; when given to children with ALL, 60% of them went into remission, a rate that increased to 90% when combined with prednisone. The incidence of remission was not increased significantly when vincristine, prednisone, and L-asparaginase were combined, but it was noted that when all three agents were used remissions lasted longer.