The value of combination therapy in adult acute myeloid leukemia with central nervous system involvement

Abstract

Background and objective: In adult patients with acute myeloid leukemia (AML), central nervous system (CNS) involvement is a rare event and treatment has not yet been defined. Because there are no definitive data as to the most appropriate therapeutic approach to CNS leukemia in AML, we retrospectively analyzed a cohort of AML patients with meningeal leukemia in order to increase our knowledge on this particular matter.

Methods: Out of 410 patients with de novo AML observed at our Institute from 1986 to 1995, 9 (2.2%) showed CNS leukemia (CNSL) during the follow-up. CNSL was treated as follows: in a first group of 4 patients we combined systemic HD Ara-C 3 g/m2 (every 12 hours by 3-hour infusion, for 6 doses), cranial radiation therapy and intrathecal (IT) methotrexate (MTX); a second group of 4 patients was treated with HD Ara-C, IT MTX without cranial irradiation; HD Ara-C alone was administered in one patient.

Results: All patients of the first group and 2 patients of the second who achieved a complete remission (CR) had a median survival of 10 months (range 5-25+) after CNS involvement, while for the non-remitters it was 2 months (range 1-5). The only patient still living underwent allogeneic bone marrow transplantation.

Interpretation and conclusions: The combination treatment of HD Ara-C, IT MTX and cranial irradiation is well tolerated and seems to be an effective therapy for CNSL, presenting a high incidence of neurologic CR that correlates with a longer survival. As expected, the number of AML patients with CNSL was small, due to the fact that CNS in those patients is a rare complication. However, this study provides further information about the therapeutic possibilities in such restricted subsets of AML patients.