Mayo Clinic: Mayo Clinic researchers have found that azathioprine, a drug commonly used to treat autoimmune disease, may increase the risk of myeloid neoplasms. Myeloid neoplasms include a spectrum of potentially life-threatening bone marrow disorders, such as myelodysplastic syndromes and acute myeloid leukemia. The results are published in JAMA Oncology. Researchers analyzed more than 40,000 patient cases with 27 common autoimmune diseases, such as Lupus, rheumatoid arthritis, among others, that were seen over a decade at Mayo Clinic. They identified 86 patients with therapy-related myeloid neoplasm. Detailed data on each patient’s drug exposures, duration and disease characteristics were collected and compared to autoimmune patients without bone marrow disorders of myelodysplastic syndromes or acute myeloid leukemia. The results concluded that only azathioprine was statistically significantly associated with an increased risk of therapy-related myeloid neoplasm. However, other agents used showed a similar trend that was not statistically significant.
“Similar associations were already documented in case reports and
case series, but have never been evaluated in a broad spectrum of
autoimmune diseases in that many patients and in context of individual
medications,” says Raoul Tibes, M.D., Ph.D.,
senior author of the study and former director of the Acute and Chronic
Leukemia Program at Mayo Clinic’s Arizona campus. “Interestingly, there
was no association with length of time on therapy and resulting myeloid
“This study, along with our current knowledge of therapy-related
myeloid neoplasm, suggests that individualized drug selection and
monitoring during treatment could be possible,” says Natalie
Ertz-Archambault, M.D., co-author of the study. “Future genomic
profiling studies may help to identify patients at risk for myeloid
neoplasms when exposed to azathioprine or other drugs,” adds Dr. Tibes.
The researchers emphasize that, while the results of the study are
intriguing, they should not change or replace the clinical judgments,
monitoring and current standard treatments at this stage for patients
with an autoimmune disease.
Despite its large size, the researchers note this study’s
limitations. It was a retrospective study. Many different autoimmune
diseases were analyzed, which can each affect the results. Only
myelodysplastic syndromes and acute myeloid leukemia were assessed. And
no definitive causal association was made between taking a particular
drug and myelodysplastic syndromes or acute myeloid leukemia. Further,
the number of patients with autoimmune disease developing
myelodysplastic syndromes or acute myeloid leukemia is still low
overall, and no prediction for individual patients can be concluded from
The researchers plan to perform molecular investigations into the
genetic susceptibility for therapy-related myeloid neoplasm as the next
phase of the study.