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Asparaginase-Induced Megaloblastic Changes

Neil E. Kay, MD; James A. Stockman III, MD; Marie J. Stuart, MD; Arlan J. Gottlieb, MD; Frank A. Oski, MD
JAMA. 1973;226(6):673. doi:10.1001/jama.1973.03230060049021.
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To the Editor.—  Chemotherapeutic agents, such as mercaptopurine, that impair cellular deoxyribonucleic acid (DNA) metabolism may produce megaloblastic changes in marrow erythroid and myeloid cells.1 Although asparaginase has been demonstrated to inhibit protein synthesis,2,3 no reports have linked its use to the production of morphologic abnormalities in the bone marrow.4,5We wish to report the occurrence of megaloblastic changes in the bone marrow of five patients receiving asparaginase.

Case Material.—  The patients ranged in age from 2 to 18 years. All had acute lymphocytic leukemia. Serum vitamin B12 and folate levels and quantitative 24-hour excretions of methylmalonic acid were determined in two patients and were normal.Prior medication consisted of vincristine, prednisone, mercaptopurine, and methotrexate in four patients, but none in the fifth. Asparaginase, 200 units/kg of body weight, was given intravenously on alternate days in six doses for two patients, daily in ten doses for


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