Therapy of CNS leukemia with intraventricular chemotherapy and low-dose neuraxis radiotherapy.
Successful treatment of CNS leukemic relapse has been frustrated by frequent local recurrence and eventual marrow relapse. We describe the treatment of meningeal leukemia in 39 children with intrathecal remission induction followed by the placement of an Ommaya reservoir to facilitate the administration and distribution of chemotherapeutic agents into the CSF. Six hundred or 900 rad of craniospinal radiation and maintenance intraventricular and intrathecal chemotherapy was then administered. Systemic reinduction therapy was added in the later cases. Sixteen children (41%) experienced no further events, with 17+ months to 13+ years (median, 25 months) follow-up . Eleven patients (28%) had CNS recurrence, nine (23%) bone marrow (BM) relapse, and two (5%) testicular relapse as the next adverse event. The course of patients with first isolated CNS relapse differed from that of the others. Eleven (69%) of 16 patients treated for first isolated CNS relapse are alive and 9 are event free, while only 35% of patients whose CNS relapse occurred simultaneously or after recurrent disease at other sites are alive (P = .04). Seven of 23 in the later group are event free. The difference is due to the increased incidence of BM relapse in the later group (30% v 6%; P = .04). For patients with first isolated CNS relapse, the life-table median CNS remission duration is 42 months. The projected CNS relapse-free survival and event-free survival 8 to 10 years after CNS relapse are 40% and 32%, respectively. Headache, nausea, and emesis of short duration were frequent during therapy. In three patients, the reservoir had to be removed for infection. No patient suffered neurologic deficit related to the reservoir. The therapy described can reduce the CNS relapse rate with manageable toxicity. Systemic relapse is still a major problem after multiple CNS relapse and in those in whom the CNS relapse follows or is simultaneous with relapse at other sites.
D000293:Adolescent; D001921:Brain / Q000528:radiation effects*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D011879:Radiotherapy Dosage; D012008:Recurrence
D004338:Drug Combinations; D003561:Cytarabine; D008727:Methotrexate