Linked Life Data

10216075

Source:http://linkedlifedata.com/resource/pubmed/id/10216075

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1999-5-18
pubmed:abstractText
6-Mercaptopurine (6MP) and methotrexate are the backbone of continuation therapy for childhood acute lymphoblastic leukemia (ALL). In studies of oral 6MP and methotrexate, indices of chronic systemic exposure to active metabolites of these agents, namely, red blood cell (RBC) concentrations of methotrexate polyglutamates (MTXPGs) and thioguanine nucleotides (TGNs) have positively correlated with event-free survival (EFS). Our objective was to evaluate whether MTXPGs, TGNs, and the dose intensity of administered methotrexate and 6MP were prognostic in the setting of a treatment protocol in which all treatment was coordinated through a single center, and the weekly doses of methotrexate were given parenterally. On protocol Total XII, 182 children achieved remission and received weekly methotrexate 40 mg/m2 parenterally and daily oral 6MP, interrupted every 6 weeks during the first year by pulse chemotherapy. A total of 709 TGN, 418 MTX-PG, and 267 thiopurine methyltransferase (TPMT) measurements, along with complete dose intensity information (dose received divided by protocol dose per week) for 19,046 weeks of 6MP and methotrexate, were analyzed. In univariate analyses, only higher dose intensity of 6MP and of weekly methotrexate were significant predictors of overall EFS (P =.006 and. 039, respectively). The occurrence of neutropenia was associated with worse outcome (P =.040). In a multivariate analysis, only higher dose intensity of 6MP (P =.020) was a significant predictor of EFS, with lower TPMT activity (P =.096) tending to associate with better outcome. 6MP dose intensity was also associated (P =.007) with EFS among patients with homozygous wild-type TPMT phenotype. Lower 6MP dose intensity was primarily due to missed weeks of therapy and not to reductions in daily dose. We conclude that increased dose-intensity of oral 6MP is an important determinant of EFS in ALL, particularly among those children with a homozygous wild-type TPMT phenotype. However, increasing intensity of therapy such that neutropenia precludes chemotherapy administration may be counterproductive.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2817-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10216075-6-Mercaptopurine, pubmed-meshheading:10216075-Administration, Oral, pubmed-meshheading:10216075-Antimetabolites, Antineoplastic, pubmed-meshheading:10216075-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:10216075-Child, pubmed-meshheading:10216075-Disease-Free Survival, pubmed-meshheading:10216075-Dose-Response Relationship, Drug, pubmed-meshheading:10216075-Drug Administration Schedule, pubmed-meshheading:10216075-Humans, pubmed-meshheading:10216075-Methotrexate, pubmed-meshheading:10216075-Methyltransferases, pubmed-meshheading:10216075-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:10216075-Prognosis, pubmed-meshheading:10216075-Proportional Hazards Models, pubmed-meshheading:10216075-Remission Induction, pubmed-meshheading:10216075-Survival Rate
pubmed:year
1999
pubmed:articleTitle
Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia.
pubmed:affiliation
Departments of Pharmaceutical Sciences, Hematology/Oncology, and Biostatistics and Epidemiology, St Jude Children's Research Hospital, Memphis, TN, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't