Azathioprine: Association with Therapy-related Myelodysplastic Syndrome and Acute Myeloid Leukemia

Objective. Azathioprine is widely used in patients with autoimmune diseases and after organ allo-grafting. 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 go (range 19-750) before t-MDS/AML developed. Results. In 11 patients, repeated episodes of cytopenias developed during azathioprine therapy, antedating 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. (First Release Jan 15 2010; J Rheumatol 2010 37:485-90, doi:10.3899/jrheum.090834)