Methotrexate polyglutamate levels and co-distributions in childhood acute lymphoblastic leukemia maintenance therapy.
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
Nielsen, Stine Nygaard
Jonsson, Olafur Gisli
MetadataShow full item record
CitationMethotrexate polyglutamate levels and co-distributions in childhood acute lymphoblastic leukemia maintenance therapy. 2019, 83(1):53-60 Cancer Chemother Pharmacol
AbstractMethotrexate polyglutamates (MTXpg) facilitate incorporation of thioguanine nucleotides into DNA (DNA-TG, the primary cytotoxic thiopurine metabolite and outcome determinant in MTX/6-mercaptopurine treatment of childhood ALL). We hypothesized that mapping erythrocyte levels of MTXpg with 1-6 glutamates and their associations with DNA-TG formation would facilitate future guidelines for maintenance therapy dosing. Summed MTX with 1-6 glutamates resolved by LCMS [median (interquartile): 5.47 (3.58-7.69) nmol/mmol hemoglobin] was in agreement with total MTX by radio ligand assay. In 16,389 blood samples from 1426 ALL maintenance therapy patients, MTXpg3 21.0 (15.2-27.4)% was the predominant metabolite, and MTXpg1 (the maternal drug) constituted 38.6 (27.2-50.2)% of MTXpg1-6. All subsets correlated; the strongest associations were between metabolites with similar polyglutamate lengths. Correlations of MTXpg1 with MTXpg2 and MTXpg3,4,5,6 were r Measuring erythrocyte MTXpg4 simplifies and can replace longer chain MTXpg monitoring. Resolving individual MTXpg identifies samples that are unsuitable for dose guidance due to high levels of MTXpg1 remaining in the plasma fraction because of recent MTX intake. All tested MTXpg subsets correlated with DNA-TG and may be used for ALL maintenance therapy dose adjustments, but the most informative subset remains to be identified.
DescriptionTo access publisher's full text version of this article click on the hyperlink below
- Methotrexate Polyglutamate Values in Children and Adolescents With Acute Lymphoblastic Leukemia During Maintenance Therapy.
- Authors: Kandikonda P, Bostrom B
- Issue date: 2019 Aug
- 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.
- Authors: Schmiegelow K, Schrøder H, Gustafsson G, Kristinsson J, Glomstein A, Salmi T, Wranne L
- Issue date: 1995 Feb
- Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.
- Authors: Masson E, Relling MV, Synold TW, Liu Q, Schuetz JD, Sandlund JT, Pui CH, Evans WE
- Issue date: 1996 Jan 1
- Time course of methotrexate polyglutamate formation and degradation in the pre-B-leukaemia cell line Nalm6 and in lymphoblasts from children with leukaemia.
- Authors: Buchholz B, Frei E, Eisenbarth J, Weigand M, Ludwig R
- Issue date: 1996 Nov
- DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial.
- Authors: Nielsen SN, Grell K, Nersting J, Abrahamsson J, Lund B, Kanerva J, Jónsson ÓG, Vaitkeviciene G, Pruunsild K, Hjalgrim LL, Schmiegelow K
- Issue date: 2017 Apr