The role of craniospinal irradiation in adults with a central nervous system recurrence of leukemia

Abstract

Background: Although central nervous system (CNS) prophylaxis in patients with leukemia has reduced the incidence of CNS disease recurrence, it still is reported to occur in approximately 5-10% of cases, resulting in a median survival of 6 months. Craniospinal irradiation (CSI) has been shown to improve survival in children who develop a CNS recurrence of acute lymphocytic leukemia (ALL). However, to the authors' knowledge, the role of CSI in adults with a CNS recurrence of leukemia is unknown.

Methods: A retrospective review of adult patients treated with CSI for a CNS recurrence of leukemia identified 16 patients treated between 1986 and 2001. The median age of the patients was 34 years (range, 16-58 years). The diagnoses included seven patients with acute myelogenous leukemia (AML), eight patients with ALL, and one patient with chronic myelogenous leukemia in blast crisis. All patients had achieved a complete disease remission prior to the CNS recurrence. Eleven patients had an isolated CNS recurrence and 5 patients had concurrent disease identified in the blood/bone marrow. The median dose of radiation was 24 grays (Gy) (range, 18-34.5 Gy) to the cranium and 18 Gy (range, 15-30 Gy) to the spine. The median fraction size was 1.8 Gy (range, 1.5-2.0 Gy) to the cranium and 1.5 Gy (range, 1.5-2.0 Gy) to the spine. Fifteen patients were also treated with intrathecal chemotherapy.

Results: One patient failed to complete radiation treatment because of disease progression. Thirteen patients achieved a complete response in the cerebrospinal fluid (CSF). The median time to disease progression was 3 months from the first day of CSI and 7 months from CNS recurrence. The median survival was 4 months and 9 months, respectively. No CNS recurrences occurred, but there were 11 bone marrow failures, 2 patients without recurrence at > 5 years, and 3 deaths without a documented site of failure. Thirteen patients had no evidence of disease in the CSF until their death or the time of last follow-up.

Conclusions: CSI with or without intrathecal chemotherapy appears to be effective at eliminating leukemia in the craniospinal axis. However, the eradication of disease in the CNS was not found to be effective at preventing disease recurrence in the bone marrow, and despite improved control of disease in the CNS, adult patients with a CNS recurrence still had a poor prognosis. Furthermore, the rapidly fatal course of disease prevented an assessment of the durability of CNS response to irradiation.