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Safe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine

Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recomm... Full description

Journal Title: Gut 2003, Vol.52 (1), p.140-142
Main Author: Kaskas, B A
Other Authors: Louis, E , Hindorf, U , Schaeffeler, E , Deflandre, J , Graepler, F , Schmiegelow, K , Gregor, M , Zanger, U M , Eichelbaum, M , Schwab, M
Format: Electronic Article Electronic Article
Language: English
Subjects:
ALL
AZA
IBD
RBC
Quelle: Alma/SFX Local Collection
Publisher: London: BMJ Publishing Group Ltd and British Society of Gastroenterology
ID: ISSN: 0017-5749
Zum Text:
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title: Safe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine
format: Article
creator:
  • Kaskas, B A
  • Louis, E
  • Hindorf, U
  • Schaeffeler, E
  • Deflandre, J
  • Graepler, F
  • Schmiegelow, K
  • Gregor, M
  • Zanger, U M
  • Eichelbaum, M
  • Schwab, M
subjects:
  • 6-mercaptopurine
  • 6-methylthioguanine
  • 6-MP
  • 6-MTG
  • 6-TGN
  • 6-thioguanine nucleotides
  • 6-thioinosine-5′-monophosphate
  • acute lymphoblastic leukaemia
  • Adult
  • ALL
  • AZA
  • Azathioprine
  • Azathioprine - administration & dosage
  • Biological and medical sciences
  • Case Report
  • Clinical Medicine
  • Crohn Disease - drug therapy
  • Crohn Disease - enzymology
  • Crohn's disease
  • Digestive system
  • Drug Administration Schedule
  • Drug therapy
  • Evaluation
  • Female
  • Gastroenterologi
  • Gastroenterology & hepatology
  • Gastroenterology and Hepatology
  • Gastroenterology. Liver. Pancreas. Abdomen
  • Gastroentérologie & hépatologie
  • Human health sciences
  • Humans
  • IBD
  • Immunosuppressive Agents - administration & dosage
  • inflammatory bowel diseases
  • Klinisk medicin
  • Male
  • Medical and Health Sciences
  • Medical sciences
  • Medicin och hälsovetenskap
  • Methyltransferases - deficiency
  • Other diseases. Semiology
  • Pharmacology. Drug treatments
  • RBC
  • red blood cells
  • Sciences de la santé humaine
  • Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
  • thiopurine S-methyltransferase
  • TIMP
  • TPMT
  • Treatment Outcome
ispartof: Gut, 2003, Vol.52 (1), p.140-142
description: Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn’s disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0017-5749
fulltext: fulltext
issn:
  • 0017-5749
  • 1468-3288
  • 1468-3288
url: Link


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creatorKaskas, B A ; Louis, E ; Hindorf, U ; Schaeffeler, E ; Deflandre, J ; Graepler, F ; Schmiegelow, K ; Gregor, M ; Zanger, U M ; Eichelbaum, M ; Schwab, M
creatorcontribKaskas, B A ; Louis, E ; Hindorf, U ; Schaeffeler, E ; Deflandre, J ; Graepler, F ; Schmiegelow, K ; Gregor, M ; Zanger, U M ; Eichelbaum, M ; Schwab, M
descriptionThiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn’s disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.
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subject6-mercaptopurine ; 6-methylthioguanine ; 6-MP ; 6-MTG ; 6-TGN ; 6-thioguanine nucleotides ; 6-thioinosine-5′-monophosphate ; acute lymphoblastic leukaemia ; Adult ; ALL ; AZA ; Azathioprine ; Azathioprine - administration & dosage ; Biological and medical sciences ; Case Report ; Clinical Medicine ; Crohn Disease - drug therapy ; Crohn Disease - enzymology ; Crohn's disease ; Digestive system ; Drug Administration Schedule ; Drug therapy ; Evaluation ; Female ; Gastroenterologi ; Gastroenterology & hepatology ; Gastroenterology and Hepatology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastroentérologie & hépatologie ; Human health sciences ; Humans ; IBD ; Immunosuppressive Agents - administration & dosage ; inflammatory bowel diseases ; Klinisk medicin ; Male ; Medical and Health Sciences ; Medical sciences ; Medicin och hälsovetenskap ; Methyltransferases - deficiency ; Other diseases. Semiology ; Pharmacology. Drug treatments ; RBC ; red blood cells ; Sciences de la santé humaine ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; thiopurine S-methyltransferase ; TIMP ; TPMT ; Treatment Outcome
ispartofGut, 2003, Vol.52 (1), p.140-142
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8Zanger, U M
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descriptionThiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn’s disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.
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16-methylthioguanine
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46-TGN
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titleSafe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine
authorKaskas, B A ; Louis, E ; Hindorf, U ; Schaeffeler, E ; Deflandre, J ; Graepler, F ; Schmiegelow, K ; Gregor, M ; Zanger, U M ; Eichelbaum, M ; Schwab, M
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66-thioinosine-5′-monophosphate
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1Correspondence to:
 Dr BA Kaskas, Division for Inflammation, Infection, and Repair, University of Southampton, School of Medicine, Mailpoint 813, Southampton SO16 6YD, UK; b.kaskas@soton.ac.uk
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7Correspondence to: … Dr BA Kaskas, Division for Inflammation, Infection, and Repair, University of Southampton, School of Medicine, Mailpoint 813, Southampton SO16 6YD, UK; b.kaskas@soton.ac.uk
abstractThiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn’s disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.
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