title: Pancytopenia due to high 6-methylmercaptopurine levels in a 6-mercaptopurine treated patient with Crohn's disease.
abstract: In a 23-year-old female with colonic Crohn's disease 6-mercaptopurine 100 mg daily (1.7 mg/kg) was added to mesalamine and prednisolone therapy because of ongoing disease activity. One month later she had fever and a pancytopenia. 6-methylmercaptopurine ribonucleotides levels were extremely elevated (57,000 pmol/8x10(8) red blood cells) and 6-thioguanine nucleotides levels were subtherapeutically (126 pmol/8x10(8) red blood cells). Genotyping showed a wildtype thiopurine S-methyltransferase TPMT(H/H) (*1/*1) genotype and a wildtype inosine triphosphate pyrophosphatase gene. TPMT and inosine triphosphate pyrophosphatase activity were normal. The pancytopenia recovered spontaneously within a few weeks, parallel with decreasing 6-methylmercaptopurine ribonucleotides levels after interrupting 6-mercaptopurine treatment. Epstein-Barrvirus, Cytomegalovirus and Herpesvirus infections were excluded by serology. This is the first report of pancytopenia due to extremely high 6-methylmercaptopurine ribonucleotides levels. No relation was found with the genotype of TPMT and inosine triphosphate pyrophosphatase enzymes, which play key roles in the thiopurine metabolic pathway. Apparently, 6-methylmercaptopurine ribonucleotides metabolites can cause pancytopenia, as was already known for 6-thioguanine nucleotides.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Maastricht (azM), P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. lgi@sint.azm.nl
authors.forename: L P L
authors.initials: LP
authors.lastname: Gilissen
authors.forename: L J J
authors.initials: LJ
authors.lastname: Derijks
authors.forename: H M J H
authors.initials: HM
authors.lastname: Verhoeven
authors.forename: J
authors.initials: J
authors.lastname: Bierau
authors.forename: P M
authors.initials: PM
authors.lastname: Hooymans
authors.forename: D W
authors.initials: DW
authors.lastname: Hommes
authors.forename: L G J B
authors.initials: LG
authors.lastname: Engels
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015122:Mercaptopurine / Q000009:adverse effects* / Q000097:blood; D008780:Methyltransferases / Q000235:genetics; D010198:Pancytopenia / Q000139:chemically induced*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000097:blood; D013873:Thionucleotides / Q000097:blood
chemical_list: D013873:Thionucleotides; D013868:Thioinosine; C002344:6-methylthiopurine ribonucleoside-5'-phosphate; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase