Abstract
Objective.Azathioprine is widely used in patients with autoimmune diseases and after organ allografting. A recognized carcinogen, azathioprine is also associated with the development of therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML).Methods.In 56 reported cases, azathioprine had been administered for a median of 65 months (range 6–192) to a median cumulative dose of 146 g (range 19–750) before t-MDS/AML developed.Results.In 11 patients, repeated episodes of cytopenias developed during azathioprine therapy, ante-dating the development of t-MDS/AML. In 33 cases with successful karyotypic analysis, 26 cases (79%) showed monosomy 7, deletion of the long arm of chromosomes 7 and 5, and rearrangement of chromosome 11q23. These changes were cytogenetic hallmarks of MDS/AML secondary to known leukemogenic agents and radiotherapy.Conclusion.The observations implicate azathioprine as a leukemogenic agent. It will be prudent to review the need for azathioprine therapy when unexpected cytopenias occur and prescription has been prolonged.
Publisher
The Journal of Rheumatology
Subject
Immunology,Immunology and Allergy,Rheumatology
Cited by
38 articles.
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