RT Journal Article
SR Electronic
T1 Azathioprine: Association with Therapy-related Myelodysplastic Syndrome and Acute Myeloid Leukemia
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.090834
DO 10.3899/jrheum.090834
A1 Yok-Lam Kwong
YR 2010
UL http://www.jrheum.org/content/early/2010/01/11/jrheum.090834.abstract
AB 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, 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.