TY - JOUR T1 - Azathioprine: Association with Therapy-related Myelodysplastic Syndrome and Acute Myeloid Leukemia JF - The Journal of Rheumatology JO - J Rheumatol SP - 485 LP - 490 DO - 10.3899/jrheum.090834 VL - 37 IS - 3 AU - YOK-LAM KWONG Y1 - 2010/03/01 UR - http://www.jrheum.org/content/37/3/485.abstract N2 - 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. ER -