Azathioprine: association with therapy-related myelodysplastic syndrome and acute myeloid leukemia.
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.


CONCLUSIONS
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.
Kwong
Yok-Lam
YL
Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. ylkwong@hkucc.hku.hk
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000235:genetics
D007166:Immunosuppressive Agents; D001379:Azathioprine