Clinical Investigations in the Treatment of Meningeal Leukemia: Radiation Therapy Regimens vs. Conventional Intrathecal Methotrexate

1. Using IT MTX as standard therapy for CNS leukemia, the comparative effectiveness of three radiation therapy regimens and a combination radiation-IT MTX regimen was determined by the Pediatric Division of the Southwest Cancer Chemotherapy Study Group.

2. IT MTX, 0.5 mg./Kg. every 2-3 days until the spinal fluid mononuclear cell count decreased to 10/mm³ or less, produced spinal fluid remissions in 78 per cent of 51 children experiencing their first episode of CNS leukemia. The duration of remission ranged from 6-414 days (median 87 days). These figures are comparable to those previously reported for IT antifol therapy.

3. Radiation therapy to the entire cranium using tumor doses of 500 rads and 1000 rads was ineffective in normalizing the CSF, although symptomatic relief was often obtained.

4. Radiation of the entire cerebrospinal axis using a tumor dose of 1000 rads resulted in a spinal fluid remission rate of 92 per cent. Remissions persisted for 13-527 days (median 52 days). Six of seven children in marrow remission when radiation therapy was administered showed evidence of myelosuppression.

5. A combination therapy regimen with two injections of MTX preceding radiation of the entire cerebrospinal axis (750-1000 rads tumor dose for children in marrow remission and 250-500 rads tumor dose for children in marrow relapse) and one injection of MTX intrathecally following radiation resulted in spinal fluid remission in 100 per cent of the evaluable children in the treatment group. Symptomatic remissions occurred in 94 per cent of the children. The duration of remission, however, was similar to that obtained with conventional IT MTX therapy. Evidence of myelosuppression appeared in half of the children in bone marrow remission.

6. None of the radiation regimens was superior to IT MTX when the following parameters were considered: (1) duration of CNS remission; (2) duration of existing bone marrow remission; (3) survival from onset of meningeal leukemia; and (4) number of CNS relapses.