Azathioprine‐associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S ‐methyltransferase deficiency

Immunosuppressive thiopurines like azathioprine, 6‐mercaptopurine, and thioguanine are commonly used in inflammatory and neoplastic disorders. A subset of these patients are genetically slow metabolizers due to point‐mutations in enzyme thiopurine S ‐methyltransferase (TPMT), and are at a higher risk of hematologic toxicity and leukemogenesis. We present such a patient who was a slow metabolizer for azathioprine, and developed a rapidly lethal form acute myeloid leukemia after relatively low dose exposure to the drug. There was prominent hemophagocytic activity in the bone marrow, and cytogenetic analysis showed a complex karyotype with monosomy 7, but no involvement of chromosome 8. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.