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November 5, 1973, Vol 226, No. 6 >
ARTICLE | November 5, 1973

Asparaginase-Induced Megaloblastic Changes FREE

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):673-673. doi:10.1001/jama.1973.03230060049021
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References

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

REFERENCES

1 +
Chanarin I: Megaloblastic Anemia Secondary to Other Disorders and to Drugs: The Megaloblastic Anemias . Oxford, Blackwell Scientific Publications, 908-910, 1969;.
2 +
Saunders EF:  The effect of L-asparaginase on the nucleic acid metabolism and cell cycle of human leukemic cells . Blood 39:575, 1972;.
3 +
Ellen KAO, Fabrizio AM, Jackson L:  The dependence of DNA and RNA synthesis on protein synthesis in asparaginase treated lymphoma cells . Cancer Res 30:315, 1970;.
4 +
Ho D, et al:  L-asparagine requirement and the effect of L-asparaginase on normal and leukemic human bone marrow . Cancer Res 30:466, 1970;.
5 +
Land JV, et al:  Toxicity of L-asparaginase in children with advanced leukemia . Cancer 30:339, 1970;.
6 +
Lampkin BC, Nagao T, Mauer AM:  Drug effect in acute leukemia . J Clin Invest 48:1124, 1969;.
7 +
Ernst P, Kellmann SA:  Perturbation of generation cycle of human leukemic blast cells by cytostatic therapy in vivo: Effect of corticosteroids . Blood 36:689, 1970;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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1 +
Chanarin I: Megaloblastic Anemia Secondary to Other Disorders and to Drugs: The Megaloblastic Anemias . Oxford, Blackwell Scientific Publications, 908-910, 1969;.
2 +
Saunders EF:  The effect of L-asparaginase on the nucleic acid metabolism and cell cycle of human leukemic cells . Blood 39:575, 1972;.
3 +
Ellen KAO, Fabrizio AM, Jackson L:  The dependence of DNA and RNA synthesis on protein synthesis in asparaginase treated lymphoma cells . Cancer Res 30:315, 1970;.
4 +
Ho D, et al:  L-asparagine requirement and the effect of L-asparaginase on normal and leukemic human bone marrow . Cancer Res 30:466, 1970;.
5 +
Land JV, et al:  Toxicity of L-asparaginase in children with advanced leukemia . Cancer 30:339, 1970;.
6 +
Lampkin BC, Nagao T, Mauer AM:  Drug effect in acute leukemia . J Clin Invest 48:1124, 1969;.
7 +
Ernst P, Kellmann SA:  Perturbation of generation cycle of human leukemic blast cells by cytostatic therapy in vivo: Effect of corticosteroids . Blood 36:689, 1970;.

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