During the past 10 years, 1962 to 1972, we have administered irradiation to the central nervous system (CNS) during the first few weeks of remission of acute lymphocytic leukemia (ALL) as an integral part of a treatment plan aimed at cure of ALL. Its purpose has been to eradicate residual leukemia in the CNS and thus prevent CNS relapse. The results indicate that craniospinal irradiation alone, 2400 rads, or cranial irradiation, 2400 rads, with simultaneous intrathecal methotrexate is effective in -preventing CNS relapse. This results in marked improvement in complete remission duration and a 50% frequency of long-term leukemia-free survival and possible cure. Although intermittent intrathecal methotrexate during remission is said to reduce the incidence of CNS relapse by one half, a 15-fold reduction results from adequate preventive CNS irradiation. Until a better method is found, all children with ALL should receive adequate CNS irradiation early during remission in order to prevent CNS relapse and to prolong complete remission.

Prevention of central nervous system leukemia by irradiation.

A 7-year-old boy with acute lymphocytic leukemia suffered increasing dementia, seizures, ataxia, and spasticity. The neuropathologic findings appeared unique, and included extensive fibrillary gliosis, with lesser degrees of myelin loss and axonal dystrophy. Similar though less severe findings were observed on re-examination of CNS tissues from 23 other children who died of leukemia. Subcortical fibrillary gliosis was particularly prominent in 22 of 23 cases, and occurred symmetrically in the subependymal and subpial regions, inferior olives, cerebellar roof nuclei, substantia nigra, internal and external capsules, subventricular nuclei, basis pontis, and ventral horns of the spinal cord. The subcortical fibrillary gliosis was out of proportion to the myelin pallor and was not associated with leukemic infiltration. Alzheimer Type II glia were also present diffusely in 22 of 24 cases. No clear etiologic association could be established between the severity of the neuropathologic alterations and the following actors: age at death, duration of illness, elevated intracranial pressure, or treatment regimens. However, the reported case demonstrated the most severe parenchymatous changes at autopsy and received the most intensive treatment of the CNS. This association suggests that the neurologic deterioration may be the consequence of antileukemic treatment. Additional studies to define the frequency of such CNS abnormalities and the factors leading to their development are needed.

Mary Ellen Haggard

Papers

Remission maintenance therapy for meningeal leukemia: intrathecal methotrexate vs. intravenous bis-nitrosourea.