Alison L T Ma1, Gregory Bale2, Helen Aitkenhead3, Stephen D Marks4. 1. Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. Electronic address: maalison2000@gmail.com. 2. Department of Pharmacy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 3. Department of Chemical Pathology, Great Ormond Street Hospital for Children National Health Service (NHS) Foundation Trust, London, United Kingdom. 4. Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Abstract
OBJECTIVE: To assess the profile of thiopurine transmethyltransferase (TPMT) enzyme activities in children and discuss the utility of measuring TPMT levels before commencing azathioprine therapy. STUDY DESIGN: Retrospective study in a single pediatric center of all patients who had TPMT enzyme assay measured during a 3-year period before the start of azathioprine therapy. Patients' TPMT enzyme activities were classified as normal (26-50 pmol/h/mgHb), intermediate (10-25 pmol/h/mgHb), and deficient (<10 pmol/h/mgHb). Medical and electronic prescribing records were studied, with records of patients' demographic data, diagnoses, dosages, and adverse drug reactions monitored. RESULTS: A total of 228 (45% female) patients ages 1-18 years (median 10 years) were tested for TPMT activity. They were all subsequently commenced on azathioprine. Erythrocyte TPMT activities were 14-76 (median 33.7) pmol/h/mgHb with 88% and 12% of patient having normal and intermediate activity respectively (none were deficient). The initial prescribed dosage of azathioprine was 0.7-3.5 (median 2.0) mg/kg/day. Only 2 patients developed mild neutropenia and required reduction of azathioprine dosage. CONCLUSION: This large cohort study demonstrates that the majority of pediatric patients had normal TMPT activities. We would recommend close monitoring of full blood counts after instituting azathioprine therapy but would question the cost-effectiveness of pretreatment TPMT activity in pediatric practice.
OBJECTIVE: To assess the profile of thiopurine transmethyltransferase (TPMT) enzyme activities in children and discuss the utility of measuring TPMT levels before commencing azathioprine therapy. STUDY DESIGN: Retrospective study in a single pediatric center of all patients who had TPMT enzyme assay measured during a 3-year period before the start of azathioprine therapy. Patients' TPMT enzyme activities were classified as normal (26-50 pmol/h/mgHb), intermediate (10-25 pmol/h/mgHb), and deficient (<10 pmol/h/mgHb). Medical and electronic prescribing records were studied, with records of patients' demographic data, diagnoses, dosages, and adverse drug reactions monitored. RESULTS: A total of 228 (45% female) patients ages 1-18 years (median 10 years) were tested for TPMT activity. They were all subsequently commenced on azathioprine. Erythrocyte TPMT activities were 14-76 (median 33.7) pmol/h/mgHb with 88% and 12% of patient having normal and intermediate activity respectively (none were deficient). The initial prescribed dosage of azathioprine was 0.7-3.5 (median 2.0) mg/kg/day. Only 2 patients developed mild neutropenia and required reduction of azathioprine dosage. CONCLUSION: This large cohort study demonstrates that the majority of pediatric patients had normal TMPT activities. We would recommend close monitoring of full blood counts after instituting azathioprine therapy but would question the cost-effectiveness of pretreatment TPMT activity in pediatric practice.