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 Z. Sproat, Jeanne Palmer, Ruben A. Mesa, Aref Al-Kali, James Foran, Raoul Tibes

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33 Scopus citations

Abstract

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. 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.

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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. Z., Palmer, J., Mesa, R. A., Al-Kali, A., Foran, J., & 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