Osama A.E. Ali*, Nabeel A.J.Ali1, Janan G. Hassan2
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