Azathioprine: Association with Therapy-related Myelodysplastic Syndrome and Acute Myeloid Leukemia

Kwong, Yok–Lam

doi:10.3899/jrheum.090834

Cited by 39 publications

(29 citation statements)

References 45 publications

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“…Microsatellite instability, which is a criterion used to diagnose defective MMR, is frequently found in patients with therapy-related myeloid neoplasms following thiopurine treatment. Consequently, loss of all or part of chromosome 5 or 7 is often present in therapy-related myeloid neoplasms secondary to alkylating agents as well as to AZA [14,25,26,27,28], as it was in the present case. In addition, a very similar association and chromosome abnormalities have been described in patients treated with AZA for multiple sclerosis [29].…”

Section: Discussionsupporting

confidence: 55%

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A Case of Therapy-Related Myeloid Neoplasm in a Patient with Crohn’s Disease Treated with Azathioprine

Mullier¹,

Rahier

Maignen³

et al. 2012

Acta Haematol

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Acute leukaemia (AL) has been observed in association with Crohn’s disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia. Chemotherapy was administered unsuccessfully and the patient died from this haematological disorder 9 months after diagnosis. We reviewed the current evidence on the interactions between CD, AL and AZA as well as the potential underlying mechanisms of leukaemia in AZA-treated patients. From this review, we concluded that AL should be questioned when facing cytopenia in a patient with CD. The nature of the association between AZA and AL in CD patients warrants further investigation.

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Section: Discussionsupporting

confidence: 55%

“…Patients receiving AZA therapy after organ transplantation or for autoimmune disease have been shown to be associated with a higher rate of AL [13,14,15,16,17,18,19,20,21,22]. However, in IBD the association between AZA and AL is still debated [3].…”

Section: Discussionmentioning

confidence: 99%

A Case of Therapy-Related Myeloid Neoplasm in a Patient with Crohn’s Disease Treated with Azathioprine

Mullier¹,

Rahier

Maignen³

et al. 2012

Acta Haematol

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“…Furthermore, there was a dose–effect with patients at higher doses or on long-term therapy at increased risk 3. In a further review of 25 rheumatology cases of azathioprine-treatment MDS (t-MDS), t-MDS was noted to be predominantly associated with aberrations of chromosome 7, either monosomy 7 or deletions of the long arm and, of concern, 32% of cases progressed to acute myeloid leukaemia with poor prognosis 4. In a cohort of 306 patients with t-MDS that had transformed to acute myeloid leukaemia, the 5-year survival was less than 10% 5.…”

Section: Discussionmentioning

confidence: 99%

Macrocytosis in Crohn's disease: a devastating blast

L¹,

Santharam²,

MacFaul³

2013

BMJ Case Reports

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A 47-year-old woman with a 36-month history of Crohn's disease with one previous bowel resection treated with azathioprine was found to have a persistently raised mean corpuscular volume (MCV) on routine complete blood count testing. Despite vitamin B12 replacement, her MCV remained elevated. A bone marrow biopsy was performed, which demonstrated myelodysplastic syndrome. Macrocytosis is a common abnormality in patients with Crohn's disease, most commonly due to vitamin B12 deficiency and secondarily due to bacterial overgrowth. However, it is important to recognise that myelodysplastic syndrome is a common under-reported complication of azathioprine therapy. One-third of cases progress to acute myeloid leukaemia with poor prognosis. In patients with suspected myelodysplastic syndrome, azathioprine therapy should be immediately discontinued.

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“…However, the proportion of patients treated for their underlying AIC with immunosuppressive therapies (ISTs) was not reported in this trial. In patients whose AIC is treated with IST, it is difficult to discern which potential predisposing factor is most important in the development of MDS because drugs like azathioprine and cyclophosphamide can potentially lead to secondary MDS [5,6,7]. …”

Section: Introductionmentioning

confidence: 99%

Autoimmunity and Inflammation in Myelodysplastic Syndromes

Wolach

Stone²

2016

Acta Haematol

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Autoimmune and inflammatory conditions (AICs) are encountered in up to 25% of patients with myelodysplastic syndromes (MDS). A wide range of AICs have been reported in association with MDS and can range from limited clinical manifestations to systemic diseases affecting multiple organs. Vasculitides, connective tissue diseases, and inflammatory arthritis are frequently reported in different studies; noninfectious fever and constitutional symptoms at presentation are common. Associations between AICs and specific MDS characteristics vary by study, but the available data suggest that AICs cluster more often in younger patients with higher-risk MDS. In general, AICs do not seem to confer worse survival, although certain AICs may be associated with adverse outcome (e.g. vasculitis) or progression of MDS (Sweet's syndrome). Nonetheless, these complications may have a significant impact on quality of life and affect the timing and type of MDS-directed therapy. The mainstay of management of these complications in the short term relies on immunosuppressive drugs. Increasing evidence suggests that hypomethylating agents may be effective in treating these complications and reduce steroid dependence. While the pathogenesis of AICs is incompletely understood, growing appreciation of cellular immune deregulation, cytokine hypersecretion, and the genetic heterogeneity underlying MDS may improve our understanding of common pathways linking MDS, inflammation, and autoimmunity.

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Azathioprine: Association with Therapy-related Myelodysplastic Syndrome and Acute Myeloid Leukemia

Abstract: The observations implicate azathioprine as a leukemogenic agent. It will be prudent to review the need for azathioprine therapy when unexpected cytopenias occur and prescription has been prolonged.

Cited by 39 publications

References 45 publications

A Case of Therapy-Related Myeloid Neoplasm in a Patient with Crohn’s Disease Treated with Azathioprine

A Case of Therapy-Related Myeloid Neoplasm in a Patient with Crohn’s Disease Treated with Azathioprine

Macrocytosis in Crohn's disease: a devastating blast

Autoimmunity and Inflammation in Myelodysplastic Syndromes

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