Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Andersen, Mette Klarskov
Svendsen, Anne Louise
MetadataShow full item record
CitationBlood. 2009, 113(24):6077-84
AbstractAmong 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia: influence on cure rates and risk of second cancer.
- Authors: Levinsen M, Rotevatn EØ, Rosthøj S, Nersting J, Abrahamsson J, Appell ML, Bergan S, Bechensteen AG, Harila-Saari A, Heyman M, Jonsson OG, Maxild JB, Niemi M, Söderhäll S, Schmiegelow K, Nordic Society of Paediatric Haematology, Oncology.
- Issue date: 2014 May
- Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity.
- Authors: Levinsen M, Rosthøj S, Nygaard U, Heldrup J, Harila-Saari A, Jonsson OG, Bechensteen AG, Abrahamsson J, Lausen B, Frandsen TL, Weinshilboum RM, Schmiegelow K
- Issue date: 2015 Jan
- On the malignant potential of thiopurine therapy.
- Authors: de Boer NK, van Asseldonk DP, van Bodegraven AA
- Issue date: 2009 Jun 11
- Epidemiology of therapy-related myeloid neoplasms after treatment for pediatric acute lymphoblastic leukemia in the nordic countries.
- Authors: Schmiegelow K
- Issue date: 2011
- Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia.
- Authors: Relling MV, Hancock ML, Boyett JM, Pui CH, Evans WE
- Issue date: 1999 May 1