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

25 Citations (Scopus)

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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Myelodysplastic Syndromes
Acute Myeloid Leukemia
Autoimmune Diseases
Odds Ratio
Azathioprine
Therapeutics
Neoplasms
Mycophenolic Acid
6-Mercaptopurine
Mitoxantrone
Second Primary Neoplasms
Cytotoxins
International Classification of Diseases
Psoriasis
Methotrexate
Pharmaceutical Preparations
Systemic Lupus Erythematosus
Cyclophosphamide
Medical Records
Case-Control Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia. / Ertz-Archambault, Natalie; Kosiorek, Heidi; Taylor, Gretchen E.; Kelemen, Katalin; Dueck, Amylou; Castro, Janna; Marino, Robert; Gauthier, Susanne; Finn, Laura; Sproat, Lisa; Palmer, Jeanne; Mesa, Ruben A.; Al-Kali, Aref; Foran, James M; Tibes, Raoul.

In: JAMA oncology, Vol. 3, No. 7, 01.07.2017, p. 936-943.

Research output: Contribution to journalArticle

Ertz-Archambault, N, Kosiorek, H, Taylor, GE, Kelemen, K, Dueck, A, Castro, J, Marino, R, Gauthier, S, Finn, L, Sproat, L, Palmer, J, Mesa, RA, Al-Kali, A, Foran, JM & Tibes, R 2017, 'Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia', JAMA oncology, vol. 3, no. 7, pp. 936-943. https://doi.org/10.1001/jamaoncol.2016.6435
Ertz-Archambault, Natalie ; Kosiorek, Heidi ; Taylor, Gretchen E. ; Kelemen, Katalin ; Dueck, Amylou ; Castro, Janna ; Marino, Robert ; Gauthier, Susanne ; Finn, Laura ; Sproat, Lisa ; Palmer, Jeanne ; Mesa, Ruben A. ; Al-Kali, Aref ; Foran, James M ; Tibes, Raoul. / Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia. In: JAMA oncology. 2017 ; Vol. 3, No. 7. pp. 936-943.
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title = "Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia",
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.",
author = "Natalie Ertz-Archambault and Heidi Kosiorek and Taylor, {Gretchen E.} and Katalin Kelemen and Amylou Dueck and Janna Castro and Robert Marino and Susanne Gauthier and Laura Finn and Lisa Sproat and Jeanne Palmer and Mesa, {Ruben A.} and Aref Al-Kali and Foran, {James M} and Raoul Tibes",
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TY - JOUR

T1 - Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia

AU - Ertz-Archambault, Natalie

AU - Kosiorek, Heidi

AU - Taylor, Gretchen E.

AU - Kelemen, Katalin

AU - Dueck, Amylou

AU - Castro, Janna

AU - Marino, Robert

AU - Gauthier, Susanne

AU - Finn, Laura

AU - Sproat, Lisa

AU - Palmer, Jeanne

AU - Mesa, Ruben A.

AU - Al-Kali, Aref

AU - Foran, James M

AU - Tibes, Raoul

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

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