Acute Lymphoblastic Leukemia: What Have We Learned About the Effects of This Disease and Its Treatment on the Nervous System?

Abstract

The treatment of leukemia remains the success story of cancer. The patients with acute lymphoblastic leukemia survive longer and longer, with the rates of long time remission of over 80% in children and 30-40% in adults. Therefore, increased attention is given to diagnose and prevent central nervous system (CNS) complications, not only in order to increase the survival, but also in order to prevent neurologic deterioration and the resulting decreased quality of life. CNS disease is relatively rare at diagnosis, with less than 10% of the patients being diagnosed with his condition. However, the rate of CNS involvement escalates to up to 75% in the first year, if no effective brain-targeted treatments are usedwhich justifies the need for CNS prophylaxis even in the absence of frank metastatic involvement. Classically, patients received cranial radiation. However, a significant percentage of ALL survivors that received cranial radiation now present with a discouraging array of complications, including neurodevelopmental sequelae, strokes, seizures and increased rate of secondary CNS malignancies. More recent, it was suggested that effective CNS prophylaxis can be achieved with a combination of high dose systemic chemotherapy and intrathecal chemotherapy. Though less toxic, some survivors of this approach are still plagued by neurological complications, including cognitive deficits due to the effects of chemotherapy on the developing brain. More research needs to be conducted on further decreasing the rate on CNS relapse, while minimizing the therapy effects of the brain. Our knowledge of the biological mechanisms involved in radiation and chemotherapy effects of different cerebral structures has to improve. For the ALL survivors, therapies to repair the cognitive damage caused by cancer treatments are still in infancy.