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Down syndrome and leukemia: unusual clinical aspects and unexpected methotrexate sensitivity

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Abstract

Twenty-four patients with Down syndrome and leukemia were studied. A strong male predominace (79%) was found. Age ranged between 18 months and 15 years (mean: 5 6/12); 54% of the patients were less than 4 years of age at the time of diagnosis. A preleukemic phase was noted in 6/24 patients. This phase, characterized essentially by thrombocytopenia, lasted from 2–8 months. Patients with preleukemia had unusual blast cell morphology and involvement of more than one cell line (dyserythropoiesis, hypolobulated megakaryocytes) and were probably M7 leukemias. All patients demon-strated severe methotrexate toxicity at standard methotrexate doses. Toxicity, manifesting as mouth ulcerations and bone marrow depression was seen regardless of the route of administration (oral, intrathecal or intravenous). A 30%–50% reduction of the standard dose was tolerated. Methotrexate absorption and clearance were studied in two patients and were found to be normal. We postulate that the observed toxicity of methotrexate may be due to a gene dosage effect for enzymes known to be on chromosome 21 and intervening in purine metabolism. Increased purine synthesis implies greater tetrahydrofolic acid demands and therefore greater sensitivity to an antifolate agent.

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Abbreviations

All:

acute lymphoblastic leukemia

AML:

acute myelogenous leukemia

MTX:

methotrexate

6-MP:

6-mercaptopurine

ITP:

idiopathic thrombocytopenic purpura

IV:

intravenous

po:

oral administration

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Author notes

  1. M. Peeters

    Present address: Institut de Progenèse, 45 Rue des Saints-Pères, F-75270, Paris Cedex 06, France

Authors and Affiliations

  1. Division of Haematology and Oncology, Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Ontario, Canada

    M. Peeters & A. Poon

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Peeters, M., Poon, A. Down syndrome and leukemia: unusual clinical aspects and unexpected methotrexate sensitivity. Eur J Pediatr 146, 416–422 (1987). https://doi.org/10.1007/BF00444952

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  • DOI: https://doi.org/10.1007/BF00444952

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