Intrathecal methotrexate-induced megaloblastic anemia in patients with acute leukemia.

OBJECTIVE

To evaluate the occurrence of megaloblastic anemia induced by the infusion of therapeutic or prophylactic methotrexate in patients with acute leukemia.

DESIGN

Data on 3 patients with acute leukemia receiving intrathecal methotrexate 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 folic acid. The median time for recovery of the hematologic parameters in these patients was 7 days.

CONCLUSIONS

Intrathecally administered methotrexate may result in megaloblastic changes in the bone marrow of leukemic patients. The morphologic clues suggestive of folate deficiency in patients with acute leukemia may be masked by coexisting factors, such as the effects of cytotoxic treatment, prior transfusions, or persistent changes from the leukemic clone itself. Caution should be exercised to avoid attributing these changes to the neoplastic process, since the prognosis and treatment for the conditions involved are totally different. Repeat examination of the bone marrow, obtaining folic acid and vitamin B(12) levels, and a therapeutic trial of folic acid may help identify and reverse these changes.