Azathioprine
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Pancytopenia: case report A girl developed pancytopenia during treatment with azathioprine for inflammatory bowel disease (IBD). A 12-year-old girl was diagnosed with IBD and initially received mesalazine and remained symptom-free for 15 months. She then had a relapse and cortisone and mesalazine were unsuccessful. Genotyping showed that she was heterozygous for TPMT (thiopurine Smethyltransferase )*2, wild-type for TPMT*3B and TPMT*3C, and she started receiving azathioprine 2 mg/kg/day. After 2 months, she was found to have pancytopenia (WBC count 2900/mm3, platelet count 82 000/mm3, haemoglobin 8.5 g/100mL). Her 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine ribonucleotides (6-MMP) concentrations were 3414 pmol per 8 × 108 RBCs and < 20 pmol per 8 × 108 RBCs, respectively, and TPMT activity was 3.45 nmol/h/mL RBCs. Azathioprine was changed to mesalazine and, 2 weeks later, the girl’s blood test results had normalised and 6-TGN was 906 pmol per 8 × 108 RBCs. Since the girl was considered TPMT heterozygous, azathioprine wad restarted at a dosage of 25 mg/day (0.5 mg/kg/day). After 3 weeks, her 6-TGN level had increased to 1918 pmol per 8 × 108 RBCs. Azathioprine was changed to infliximab [outcome not stated]. Further genetic analysis showed that she was heterozygous for a new mutation TPMT IVS8-1G→A. Author comment: "[T]he child was a carrier of a heterozygous composite TPMT genotype . . . carrying two TPMT variants (TPMT*2, TPMT IVS8-1G→A) responsible [for] complete TPMT deficiency, with severe myelosuppression and very high 6-TGN concentrations at standard [azathioprine] doses, remaining high after dose reduction." de Beaumais TA, et al. Characterization of a novel TPMT mutation associated with azathioprine-induced myelosuppression: Letter to the Editors. British Journal of Clinical Pharmacology 68: 770-772, No. 5, 1 Nov 2009. Available from: URL: 803004590 http://dx.doi.org/10.1111/j.1365-2125.2009.03439.x - France
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Editorial comment: This case report has been published as an abstract on two previous occasions [see Reactions 1244 p8; 801137403 and 1263 p9–10; 801149614].
0114-9954/10/1285-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
Reactions 23 Jan 2010 No. 1285
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