Lymphoma azathioprine

Immunosuppressive agents such as azathioprine and mercaptopurine (a metabohte of azathioprine) are sometimes used for the treatment of IBD. These agents are generally reserved for cases that are refractory to steroids and may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity. Cyclosporine has been of short-term benefit in acute, severe ulcerative colitis when used in a continuous infusion. 

Immunosuppressants such as azathioprine and mercaptopurine have a significant potential for adverse reactions, including bone marrow suppression, and have been associated with lymphomas (in renal transplant patients) and pancreatitis. Myelosuppression resulting in leukopenia is related to a deficiency in TPMT in some patients. 

Azathioprine s toxicity includes bone marrow suppression, gastrointestinal disturbances, and some increase in infection risk. As noted in Chapter 55, lymphomas may be increased with azathioprine use. Rarely, fever, rash, and hepatotoxicity signal acute allergic reactions. 

In one patient, azathioprine-induced lymphoma with massive liver infiltration was the probable cause of fulminant hepatic failure (SEDA-21, 381). 

Long-term treatment with azathioprine has been associated with transitional carcinoma of the bladder and non-Hodgkin s lymphoma in a single case (65). 

In cases of inflammatory bowel disease, no overall increased incidence of cancer was noted after a median of 9 years follow-up in 755 patients who had taken less than 2 mg/kg/day of azathioprine over a median period of 12.5 years (69). Only colorectal cancers (mostly adenocarcinoma) were more frequent, but their incidence was also increased in chronic inflammatory bowel diseases. More specifically, there was no excess of non-Hodgkin s lymphoma, but the power of the study to detect an increased risk of this disorder was low. 

Pitt PI, Sultan AH, Malone M, Andrews V, Hamilton EB. Association between azathioprine therapy and lymphoma in rheumatoid disease. J R Soc Med 1987 80(7) 428-9. 

Barthelmes L, Thomas KJ, Seale JR. Prostatic involvement of a testicular lymphoma in a patient with myasthenia gravis on long-term azathioprine. Leuk Lymphoma 2002 43(12) 2425-6. 

There is limited evidence of carcinogenicity of azathioprine in experimental animals. Studies with rats produced squamous cell carcinomas of the ear duct after administration at 150 mg kg in the diet for 52 weeks and lymphomas of the thymus gland under other conditions. In mice, intraperitoneal injections at 40 mg kg in 1-4-day-old offspring produced leukemia and long-term studies produced lymphoma and hemangiodothelioma of the uterus. 

Cohen S, Erturk E, Skibba J, and Bryan G (1983) Azathioprine induction of lymphomas and squamous cell carcinomas in rats. Cancer Research 43 2768-2772. 

Ito A, Mori M, and Naito M (1989) Induction of uterine hemangioendothelioma and lymphoma in (C57BL/6N X C3H/2N)F1 mice by oral administration of azathioprine. Japanese Journal of Cancer Research 80(5) 419-423. 

Immunosuppressants such as azathioprine and mercaptopurine have a significant potential for adverse reactions. Azathioprine causes bone marrow suppression and has been associated with lymphomas (in renal transplant patients), skin cancer, and pancreatitis (about 3% of patients). Some investigators believe that induction of leukopenia may be necessary for therapeutic effect. Mercaptopurine causes adverse reactions similarly to azathioprine however, there are fewer reports of lymphomas with this agent. In one cohort of IBD patients, adverse effects from mercaptopurine were as follows pancreatitis, 1.2% allergic reactions, 3.9%, significant leukopenia, 11.5% and infectious complications, 14%. Ten percent of patients who received azathioprine or mercaptopurine required discontinuation of treatment because of adverse effects. Allopurinol inhibits the metabolism of mercaptopurine, and a dosage reduction of the latter is required when the two are used in combination. 

Lewis JD, Schwatrz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn s disease Benefits outweigh the risk of lymphoma. Gastroenterology 2000 118 1018-1024. 

Allopurinol is used not only in treating the hyperuricemia associated with gout but also in the secondary hyperuricemia associated with the use of antineoplastic agents. Therefore, allopurinol may be used in the management of patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer therapy that causes elevations of serum and urinary uric acid levels. Allopurinol may interfere with the metabolism of antineoplastic agents such as azathioprine and 6-mercaptopurine. 

Azathioprine Lymphoma, skin, mesenchymal tumors, hepatolxliary system... 

Live vaccines should not be given to patients undergoing treatment with infliximab. Serious infection and neutropenia is predicted to occur if infliximab is given with anakinra. Infliximab may increase serum levels of azathioprine metabolites, and a rare T-cell lymphoma has been reported in adolescents and young adults treated with infliximab and also given azathioprine or mercaptopurine. Serum levels of infliximab appear to be unaffected by aminosalicylates, corticosteroids, ciprofloxacin or metronidazole. 

Reversible Hodgkin s lymphoma associated with Epstein-Barr virus infection during azathioprine therapy for systemic lupus erythematosus in a 47-year-old woman was attributed to azathioprine, which she had taken for several years [136 ]. A locally invasive mass associated with lymphadenop-athy in the neck regressed significantly after withdrawal of azathioprine, and after about 5 months had almost completely resolved without the need for chemotherapy. 

Reversible Hodgkin s lymphoma associated with Epstein-Barr virus occurring during azathioprine therapy for SLE. Rheumatology (Oxford) 2008 47(7) ... 

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