Yok-Lam Kwong1. 1. Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. ylkwong@hkucc.hku.hk
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.
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.
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