Therapy Related Central Nervous System Diseases in Children with Acute Lymphocytic Leukemia

Abstract

Before 1950 the prognosis for children with acute lymphocytic leukemia was uniformly poor. Despite therapy that included blood transfusion and occasionally irradiation to enlarged viscera and mediastinal masses, the majority of children who developed this disease died during the first six months following diagnosis, and rarely did a child survive beyond nine months (1). Farber’s success, reported in 1948, in achieving temporary remissions in five children with leukemia by using the folic acid antagonist 4-aminopteroyl-glutamic acid led to the development of more potent anti-leukemic drugs capable of prolonging these initial remissions (2). These early achievements demonstrated that extracranial leukemia could be controlled by chemotherapy; however, meningeal leukemia proved to be more resistant. Cranial radiation of 1500 rads or less provided temporary gains and similar attempts to eradicate leukemic cells from the central nervous system (CNS) by intrathecal injection of drugs were equally unsuccessful (3–7). Meningeal leukemia occurring during remission was usually followed by hematological relapse, leaving little chance for cure. Thus CNS leukemia was identified as one of the main obstacles to the successful treatment of acute leukemia in children.