title: Does lymphopenia or macrocytosis reflect 6-thioguanine levels in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine?
abstract: BACKGROUND
  The thiopurine drugs, 6-mercaptopurine and azathioprine, remain the mainstay of immunomodulator therapy for inflammatory bowel disease (IBD). Optimal management depends on achieving therapeutic levels of 6-thioguanine (6-TGN), but measuring thiopurine metabolites is associated with significant cost. Thiopurines cause lymphopenia and an increase in mean corpuscular volume (MCV). It is unclear whether any clinically useful correlation exists between 6-TGN levels and lymphocyte count or MCV.
  
  
  OBJECTIVE
  The aim of this study is to investigate the correlation between 6-TGN levels and lymphocyte count and MCV in thiopurine-treated patients with IBD.
  
  
  METHODS
  We analysed a prospectively acquired database of 67 patients with IBD treated with thiopurine therapy. The data were analysed looking at the relationship between 6-TGN levels and both lymphocyte count and MCV by using the Spearman's rank correlation coefficient.
  
  
  RESULTS
  Twenty-seven (40%) patients had therapeutic 6-TGN levels. Thirty-three (49%) patients had sub-therapeutic 6-TGN levels. A weak positive correlation between 6-TGN levels and lymphocyte count was demonstrated, but this was not statistically significant (Spearman's R = 0.14, P = 0.23). Spearman's rank correlation coefficient between 6-TGN levels and MCV was statistically significant (R = 0.42, P = 0.0005). MCV >101 fL excluded a subtherapeutic 6-TGN level with positive predictive value of 92%.
  
  
  CONCLUSIONS
  There is no specific lymphopenia that can be assumed to indicate a therapeutic 6-TGN level. The relationship between 6-TGN levels and MCV is likely to be clinically relevant. If MCV is elevated, 6-TGN is unlikely to be sub-therapeutic. MCV is a potential surrogate marker which can rule out sub-therapeutic thiopurine metabolites in patients with IBD treated with azathioprine or 6-mercaptopurine.
authors.affiliation: Alfred Health, Melbourne, Victoria, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: Heerasing
authors.affiliation: Barwon Health, Geelong, Victoria, Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Ng
authors.affiliation: Barwon Health, Geelong, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Dowling
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004909:Erythrocyte Indices / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D008231:Lymphopenia / Q000097:blood* / Q000175:diagnosis; D008297:Male; D015122:Mercaptopurine / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D013866:Thioguanine / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine
keywords: inflammatory bowel diseases; lymphopenia; macrocytosis; therapeutic; thiopurine metabolites