Azathioprine is a commonly used immunosuppressive agent in post-transplantation regimens and autoimmune diseases. An increased risk of lymphoma with thiopurine therapy in patients with inflammatory bowel disease has been described previously; however, there are few reported cases of azathioprine therapy-related myelodysplastic syndrome and acute myeloid leukaemia. We report two patients with ulcerative colitis who subsequently developed azathioprine-related myelodysplastic syndrome. It is imperative that gastroenterologists remain vigilant for this rare complication as this subset of patients has a particularly poor prognosis. These cases are also important in considering the risk of open-ended thiopurine therapy.
CASE 1A 68-year-old female patient with a suspected neutropenic fever was advised to attend the accident and emergency department by her general practitioner (GP). Her GP reported a neutrophil count of 0.5×10 9 / l. She described a 3 week history of night sweats, low-grade fever, increasing fatigue and shortness of breath on exertion. She had a medical history of ulcerative pancolitis diagnosed 6 years prior to this presentation and type 2 diabetes mellitus. Current medication included azathioprine 125 mg once daily, Asacol 3.2 g daily, ferrous fumarate 210 mg once daily and Calcichew D3 tablets taken twice daily. Thiopurine methyltransferase (TPMT) enzyme assay levels were within the normal range. She had not been exposed to any other immunomodulatory drugs, and her colitis had been relatively quiescent. Prior to this, she had been undergoing routine follow-ups, and her blood counts did not reveal any abnormalities. There was no family history of cancer in her first-degree relatives. Physical examination was unremarkable. Observation revealed a temperature of 37.5°C. Pulse 80 was beats/min, blood pressure 128/35 mm Hg and oxygen saturation by pulse oximetry 99% on room air.
INVESTIGATIONSBlood tests showed a haemoglobin of 8.9 g/ dl, mean cell volume (MCV) 107.5 fl, platelets 118×10 9 /l, white cell count 9.14 ×10 9 /l, neutrophils 2.84×10 9 /l, lymphocytes 3.8×10 9 /l and monocytes 2.48×10 9 /l. Blood biochemistry showed the following; urea 2 mmol/l, creatinine 52 mmol/l, sodium 139 mmol/l, potassium 3.6 mmol/l, C reactive protein 22.9 mg/l, albumin 38 g/l, bilirubin 5 mmol/l, alkaline phosphatase 66 IU/l and alanine transaminase 17 IU/l.Iron, vitamin B 12 and folate were normal.Chest radiograph was unremarkable.A peripheral blood film showed a leucoerythroblastic picture with 10% blasts on film. Bone marrow aspirate and trephine revealed 15% blasts, which were confirmed as being of myeloid origin by flow cytometry. Morphologically, there was significant dyserythropoiesis in the marrow. Cytogenetic testing by fluorescence in situ hybridization (FISH) analysis revealed monosomy 7 detected in 70% of the interphase nuclei. The findings were consistent with the diagnosis of myelodysplasia of the subtype refractory anaemia with excess blasts-2.
Outcome and follow-upThe patient was started on 5-aza...