Lymphocytopenia in patients with inflammatory bowel disease on immunosuppressive medications

Abstract

Azathioprine and 6-mercaptopurine (AZA/6MP) are effective immunosuppressives commonly used for the treatment of inflammatory bowel disease (IBD). The mercaptopurine metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine ribonucleotides (6MMP), have been suggested as surrogate markers of the safety and efficacy of immunosuppressive therapy. Elevated levels of 6TG have been found to be associated with bone marrow toxicity manifest as leukopenia. Elevated 6-MMP levels have been associated with hepatotoxicity. This study aims to evaluate the incidence of lymphocytopenia with immunosuppressive use, to correlate metabolite levels (6TG and 6MMP) with leukocyte (WBC), lymphocyte, mean corpuscle volume (MCV) levels in IBD patients treated with AZA/6MP, and secondarily to evaluate clinical status with these blood markers.\r\nMedical records of adult IBD patients taking either azathioprine or 6-mercaptopurine were analyzed based on blood counts, mercaptopurine metabolites 6TG and 6MMP, and clinical status. Eighty three percent of the patients taking AZA/6MP developed lymphocytopenia. Of those with lymphocytopenia, only 12% had low WBC counts. A low correlation of r = -0.3 (p=0.04) for 6TG to WBC counts as well as to MCV levels was found. No correlation between 6TG levels and lymphocyte counts were noted. Clinical activity to any blood markers showed no significant correlation.\r\nThis analysis shows that lymphocyte counts and not leukocyte counts should be monitored closely in patients on these immunosuppressives, and that metabolite markers do not provide information regarding who will develop lymphocytopenia. Blood markers cannot be used as a marker for disease activity although further detailed studies will need to be done. Consequences of lymphocytopenia such as opportunistic infections need to be discussed with patients prior to starting this type of therapy. \r\n