Dose reduction of coadministered 6-mercaptopurine decreases myelotoxicity following high-dose methotrexate in childhood leukemia

被引：0
作者：
U Nygaard
K Schmiegelow
机构：
[1] The Pediatric Clinic II,
[2] The University Hospital of Copenhagen,undefined
[3] Rigshospitalet,undefined
来源：
Leukemia | 2003年 / 17卷
关键词：
myelotoxicity; child; acute lymphoblastic leukemia; 6-mercaptopurine; high-dose methotrexate;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
High-dose methotrexate (HDM) given concurrently with oral 6-mercaptopurine (6 MP) may be followed by myelotoxicity, which may necessitate treatment interruption and thus interfere with the efficacy of the treatment of childhood acute lymphoblastic leukemia (ALL). Through inhibition of purine de novo synthesis and enhancement of the bioavailability, HDM may increase the incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6 MP.
引用
收藏
页码：1344 / 1348
页数：4
相关论文
共 137 条
[1]  
Gustafsson G(2000)Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation. Nordic Society of Pediatric Haematology and Oncology (NOPHO) Leukemia 14 2267-2275
[2]  
Schmiegelow K(2001)6-Mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia Leukemia 15 74-79
[3]  
Forestier E(1987)The effect of methotrexate on the bioavailability of oral 6MP Clin Pharmacol Ther 41 384-387
[4]  
Clausen N(1988)Purine Biochem Pharmacol 37 2321-2327
[5]  
Glomstein A(1995) synthesis as the basis of synergism of methotrexate and 6-mercaptopurine in human malignant lymphoblasts of different lineages J Clin Oncol 13 345-351
[6]  
Jonmundsson G(1996)Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. Nordic Society for Pediatric Hematology and Oncology Cancer Chemother Pharmacol 37 409-414
[7]  
Schmiegelow K(1996)Clinical and experimental pharmacokinetic interaction between 6MP and methotrexate Pediatr Hematol Oncol 13 433-441
[8]  
Bretton-Meyer U(1999)Myelotoxicity, pharmacokinetics, and relapse rate with methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia Gen Pharmacol 33 341-346
[9]  
Balis FM(1997)The interaction of 6-mercaptopurine (6-MP) and methotrexate (MTX) Biochemistry 36 2501-2506
[10]  
Holcenberg JS(1994)Cytotoxic mechanism of 6-thioguanine: hMutSalpha, the human mismatch binding heterodimer, binds to DNA containing S6-methylthioguanine Lancet 343 1188-1190
12345678910