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Göteborgs universitets publikationer

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.

Författare och institution:
Kjeld Schmiegelow (-); Ibrahim Al-Modhwahi (-); Mette Klarskov Andersen (-); Mikael Behrendtz (-); Erik Forestier (-); Henrik Hasle (-); Mats Heyman (-); Jon Kristinsson (-); Jacob Nersting (-); Randi Nygaard (-); Anne Louise Svendsen (-); Kim Vettenranta (-); Richard Weinshilboum (-); Berit Kriström (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för pediatrik); Lotta Mellander (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för pediatrik)
Publicerad i:
Blood, 113 ( 24 ) s. 6077-84
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Among 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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
6-Mercaptopurine, administration & dosage, adverse effects, Administration, Oral, Adolescent, Antineoplastic Combined Chemotherapy Protocols, adverse effects, Child, Child, Preschool, Combined Modality Therapy, Cranial Irradiation, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Infant, Karyotyping, Male, Methotrexate, administration & dosage, adverse effects, Methyltransferases, metabolism, Neoplasms, Second Primary, chemically induced, diagnosis, metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma, drug therapy, pathology, radiotherapy, Prognosis, Remission Induction, Risk Factors, Stem Cell Transplantation, Survival Rate, Treatment Outcome
Postens nummer:
Posten skapad:
2012-01-04 14:06
Posten ändrad:
2012-01-04 16:14

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