Severe Myelotoxicity Associated with Thiopurine S-Methyltransferase*3A/*3C Polymorphisms in a Patient with Pediatric Leukemia and the Effect of Steroid Therapy
نویسندگان
چکیده
Myelosuppression is a serious complication during treatment of acute lymphoblastic leukemia and the duration of myelosuppression is affected by underlying bone marrow failure syndromes and drug pharmacogenetics caused by genetic polymorphisms. Mutations in the thiopurine S-methyltransferase (TPMT) gene causing excessive myelosuppression during 6-mercaptopurine (MP) therapy may cause excessive bone marrow toxicity. We report the case of a 15-year-old girl with T-ALL who developed severe pancytopenia during consolidation and maintenance therapy despite reduction of the dose of MP to 5% of the standard dose. Prednisolone therapy produced a remarkable but transient bone marrow recovery. Analysis of common TPMT polymorphisms revealed TPMT *3A/*3C.
منابع مشابه
Assessment of Thiopurine–based drugs according to Thiopurine S-methyltransferase genotype in patients with Acute Lymphoblastic Leukemia
For the past half century, thiopurines have earned themselves a reputation as effective anti-cancer and immunosuppressive drugs. Thiopurine S-methyltransferase (TPMT) is involved in the metabolism of all thiopurines and is one of the main enzymes that inactivates mercaptopurine. 6-MP is now used as a combination therapies for maintenance therapy of children with acute lymphocytic leukemia (A...
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BACKGROUND The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT*2 (238G>C), TPMT*3B (c.460G>A), TPMT*3A (c.460G>A and c.719A>G) and TPMT*3C (c.719A>G). The aim of the present study was to determine the frequency of TPMT polymorphisms and their...
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To the Editor, I read the paper by Belen et al. published in a recent issue of this journal with great interest [1]. They reported a 15-year-old girl with T-ALL who developed severe pancytopenia during consolidation and maintenance therapy despite dose reduction of 6-mercaptopurine (MP). They found thiopurine S-methyltransferase (TPMT) *3A/*3C polymorphisms upon TPMT genotyping. Prednisolone th...
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