Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia

Natalie Ertz-Archambault, Heidi Kosiorek, Gretchen E. Taylor, Katalin Kelemen, Amylou Dueck, Janna Castro, Robert Marino, Susanne Gauthier, Laura Finn, Lisa Sproat, Jeanne Palmer, Ruben A. Mesa, Aref Al-Kali, James M Foran, Raoul Tibes

Research output: Contribution to journalArticle

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Abstract

Results: Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed.

Conclusions and Relevance: In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Importance: Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.

Objective: To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.

Design, Setting, and Participants: This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio.

Main Outcomes and Measures: Odds ratio (OR) assessment for AID-directed therapies.

Original languageEnglish (US)
Pages (from-to)936-943
Number of pages8
JournalJAMA oncology
Volume3
Issue number7
DOIs
StatePublished - Jul 1 2017

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  • Medicine(all)

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Ertz-Archambault, N., Kosiorek, H., Taylor, G. E., Kelemen, K., Dueck, A., Castro, J., Marino, R., Gauthier, S., Finn, L., Sproat, L., Palmer, J., Mesa, R. A., Al-Kali, A., Foran, J. M., & Tibes, R. (2017). Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia. JAMA oncology, 3(7), 936-943. https://doi.org/10.1001/jamaoncol.2016.6435