Approximately 10% of patients who have received appropriate CNS prophylaxis will develop relapse in the CNS. Systemic relapse can often be identified simultaneously or shortly after CNS relapse is documented. Therefore, it is generally recommended that in addition to the treatment for CNS disease, patients should receive systemic reinduction chemotherapy. Treatment of established CNS disease often requires a combination of radiotherapy and intrathecal chemotherapy. The radiotherapy should be administered to the whole brain, consisting of 1800-2400 cGy (in 150- to 200-cGy fractions). Higher doses should be avoided due to both the risk of late toxicity (such as cognitive deficits or necrosis) as well as the potential later requirement of total body irradiation as part of the conditioning regimen for an allogeneic transplant. In addition, despite encouraging results in children, spinal radiotherapy should be avoided in adults, as the dose of radiotherapy to marrow-bearing areas subsequently limits the ability to administer necessary systemic chemotherapy. Furthermore, although this approach can help control the CNS disease, it does not prolong survival, as these patients typically succumb to relapsed system disease.53 Intrathecal or intraventricular therapy for patients with established CNS disease should include methotrexate (12-15 mg) or ara-C, preferably administered intraven-tricularly via an Ommaya reservoir. It should be administered as often as two to three times per week with at least 1 day off between doses until the cerebrospinal fluid (CSF) is cleared of leukemic blasts, then twice a week for 2-3 weeks, and then twice a month for 2 or 3 additional months (total of 8-12 doses). Patients who develop CNS disease despite prophylaxis with intrathe-
cal methotrexate, and those patients who do not clear the blasts promptly from the CSF (within two treatments), should receive intraventricular therapy with ara-C at a dose of 60 mg.
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