Intrathecal methotrexate-induced megaloblastic anemia in patients with acute leukemia

Objective-To evaluate the occurrence of megaloblastic anemia induced hy the infusion of therapeutic or prophylactic methotrexate in patients with acut e leukemia. Design.-Data on 3 patients with acute leukemia receiving intrathecal methot rexate were prospectively analyzed. Setting.-Large tertiary-care center. Results.-All 3 patients with acute leukemia developed megaloblastic anemia confirmed by examination of the bone marrow aspirate and biopsy, Two of the 3 patients had low folic acid levels, while all patients had normal serum B-12 levels. All patients responded favorably to a therapeutic trial of fol ic acid. The median time for recovery of the hematologic parameters ire the se patients was 7 days. Conclusions.-Intrathecally administered methotrexate may result in megalobl astic changes in the bone marrow of leukemic patients. The morphologic clue s suggestive of folate deficiency in patients with acute leukemia may be ma sked by coexisting factors, such as the effects of cytotoxic treatment, pri or transfusions, or persistent changes from the leukemic clone itself. Caut ion should be exercised to avoid attributing these changes to the neoplasti c process, since the prognosis and treatment for the conditions involved ar e totally different, Repeat examination of the bone marrow, obtaining folic acid and vitamin B-12 levels, and a therapeutic trial of folic acid may he lp identify and reverse these changes.