PRE-SCREENING TPMT STATUS OF LIVER TRANSPLANT PATIENTS FOR AZATHIOPRINE THERAPYâ€“A SINGLE CENTRE EXPERIENCE FROM SOUTH INDIA
Keywords:Azathioprine, Immunosuppressive regimens, Liver transplantation, Myelosuppression, Thiopurine methyltransferase, TPMT genotype testing
Objective: To assess azathioprine-induced bone marrow toxicity and its correlation with thiopurine methyltransferase (TPMT) mutation in liver transplant patients who develop myelosuppression while on azathioprine therapy.
Methods: A prospective observational study was conducted from 1st September 2014 to 30thJune 2015 on 60 liver transplant patients who were tested for TPMT allele activity prior to receiving azathioprine. Haemoglobin levels, platelet counts and white blood cell counts of the patients were monitored for the occurrence of myelotoxicity. Patients who underwent liver transplant during the retrospective period from 1st September 2011 to 31st August 2014 and who developed myelosuppression while on azathioprine therapy were also tested for TPMT genotype.
Results: A total of 76 liver transplant patients were tested for TPMT mutation. Prevalence of TPMT mutation in the study patients was 3.95%. The heterozygous TPMT*1/*3C genotype was traced in 2.63% of the patients while 1.32% of patients were homozygous for TPMT*3C allele. Interestingly 43.4% of patients with wild allele also showed azathioprine-induced myelosuppression. Azathioprine dose of 100 mg showed a higher degree of myelotoxicity than lower doses. Haematological indices of 42.1% of patients normalised on cessation of azathioprine therapy.
Conclusion: Myelosuppression following the introduction of azathioprine was observed in patients with both â€˜mutant' and â€˜wild-type' alleles. Therefore a cautious approach has to be taken in pre-screening liver transplant recipients for TPMT allele determination in our population. The absence of TPMT mutation does not ensure freedom from myelosuppression. Hence regular monitoring of haematological indices of such patients receiving thiopurine therapy should be continued.
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