Thiopurine methyl transferase enzyme activity-relationship to the dose and adverse effects of 6-mercaptopurine in children with acute lymphoblastic leukemia

Osama A.E. Ali*, Nabeel A.J.Ali¹, Janan G. Hassan^2
1MBChB, PhD, Department of Pharmacology, College of Medicine, University of Basrah, Basrah, Iraq
²MBChB,FICMS, Department of Pediatrics, College of Medicine, University of Basrah, Basrah, Iraq

A B S T R A C T
Background: There are genetic variations in the activity of the enzyme thiopurine methyl transferase (TPMT) which lead to differences in the rate of metabolism of the thiopurine drugs, especially Mercaptopurine (6-MP) which may predispose patients to the toxic effects of these drugs or therapeutic failure might occur in the children with acute lymphoblastic leukemia (ALL). Methods: Children with ALL (80) were included in the study ,of them (15)patients were  newly diagnosed and  (65)patients on maintenance treatment ,we also studied apparently normal (78)children .Serum samples were collected from each patient and healthy children for  the estimation of TPMT  activity by ELISA (Enzyme –linked immune sorbent assay ) and measurement various blood parameters Results: In normal children group, TPMT concentration was distributed as 28.3%  had low, 17.9% had intermediate and 53.8%  had normal or high activity. In the newly diagnosed group have TPMT concentration distributed as 66.7% low, 13.3%   intermediate and 20% had normal or high activity. They have a reduction in all blood parameters, for Hb level (9.92± 2.06 g/dL) ,WBC count (4184±1068.6 /mm³), Neutrophil (1537.3 ± 2142.7/mm³ ) and  platelets(157533 ± 99609/mm³).The maintenance group  have TPMT concentration  distributed as  67.7%  low,  21.5% intermediate  and 10.8% had  normal or high activity , they had a reduction in all blood parameters, for Hb level  (10.49 ±1.73g/dL),WBC count (3657 ± 1036.8/mm³), Neutrophil (1434.7 ± 1180.7/mm³ ) and  for platelets (219292 ± 133981/mm³).There was a significant (p <0.001) correlation between TPMT concentration level and blood parameters (Hb , WBC, neutrophil and platelets) in the  maintenance group of ALL  children. Conclusions: Despite the variation in the level of TPMT in patients with ALL, it is useful as guide for the dose of 6-mp determination initially in the newly diagnosed and for the dose adjustment in the maintenance group.
Keywords: TPMT, ALL, 6-MP, Children, Leukemia