Abstract
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.
Highlights
Myelosuppression is a serious complication of chemotherapy in children with acute lymphoblastic leukemia (ALL)
We here describe the case of a 15-year-old girl with ALL and thiopurine S-methyl transferase (TPMT) *3A/*3C and methylenetetrahydrofolate reductase (MTHFR) polymorphisms who suffered from severe bone marrow suppression persisting during the consolidation and maintenance therapy
Interruption of chemotherapy for 6-8 weeks and granulocyte colony-stimulating factor (G-CSF) therapy resulted in absolute neutrophil count (ANC) recovery initially without significant increase in Hb levels or platelet counts, but the duration of bone marrow suppression was prolonged as 6-MP exposures increased, suggesting that myelotoxicity is dose-dependent
Summary
Myelosuppression is a serious complication of chemotherapy in children with acute lymphoblastic leukemia (ALL). The levels of active MP metabolites are elevated during MP therapy in patients who carry TPMT mutations with decreased enzyme activity such as TPMT *2 (G238C), TPMT *3A (G460A and A719G), and TPMT *3C (A719G), leading to excessive bone marrow toxicity and being more profound in those with 2 as compared to 1 nonfunctional allele [2,3,4,5,6]. We here describe the case of a 15-year-old girl with ALL and TPMT *3A/*3C and MTHFR polymorphisms who suffered from severe bone marrow suppression persisting during the consolidation and maintenance therapy.
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Schedule a callMore From: Turkish journal of haematology : official journal of Turkish Society of Haematology
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