| Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib. | |
| | |
MedLine Citation:
|
PMID: 20421539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: Organic cation transporter-1 (OCT-1) activity (OA), a measure of the OCT-1-mediated influx of imatinib into CML mononuclear cells (MNCs), is predictive of major molecular response (MMR) at 12 and 24 months in patients with untreated CML. We now report the impact of OA on loss of response, disease transformation, and survival after 5 years of imatinib. PATIENTS AND METHODS: OA is defined as the difference in intracellular concentration of carbon-14-imatinib with and without OCT-1 inhibition. OA was measured in blood from 56 patients with untreated chronic-phase CML. RESULTS: More patients who had high OA (ie, > median OA value) achieved MMR by 60 months compared with patients who had low OA (89% v 55%; P = .007). A low OA was associated with a significantly lower overall survival (87% v 96%; P = .028) and event-free survival (EFS; 48% v 74%; P = .03) as well as a higher kinase domain mutation rate (21% v 4%; P = .047). These differences were highly significant in patients who averaged less than 600 mg/d of imatinib in the first 12 months but were not significant in patients averaging >/= 600 mg/d. Patients with very low OA (ie, quartile 1) were the only group who developed leukemic transformation (21% in quartile 1 v 0% in all other quartiles; P = .002). CONCLUSION: Measurement of OA pretherapy is a predictor for the long-term risk of resistance and transformation in patients with imatinib-treated CML. Early dose-intensity may reduce the negative prognostic impact of low OA. We propose that OA could be used to individualize dosage strategies for patients with CML to maximize molecular response and optimize long-term outcome. |
| | |
Authors:
|
Deborah L White; Phuong Dang; Jane Engler; Amity Frede; Stephanie Zrim; Michael Osborn; Verity A Saunders; Paul W Manley; Timothy P Hughes |
Related Documents
:
|
20072149 - Trisomy 11 in myelodysplastic syndromes defines a unique group of disease with aggressi... 2386769 - Detection of residual bcr/abl transcripts in chronic myeloid leukaemia patients in comp... 8558939 - Allopurinol inhibits de novo purine synthesis in lymphoblasts of children with acute ly... 1058669 - Cytogenetic studies of the spleen in chronic granulocytic leukaemia. 3166449 - Prediction of impending blast cell transformation in chronic granulocytic leukaemia. 6937219 - The significance of splenomegaly in 101 adults with acute lymphoblastic leukemia (all) ... 17028119 - A magnetic resonance imaging study of patients with parkinson's disease with mild cogni... 22539539 - The relative impact on leg symptoms of fears of getting varicose veins and of great sap... 8912479 - The prognosis of rheumatoid arthritis. |
Publication Detail:
|
Type: Clinical Trial, Phase II; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-26 |
Journal Detail:
|
Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 28 ISSN: 1527-7755 ISO Abbreviation: J. Clin. Oncol. Publication Date: 2010 Jun |
Date Detail:
|
Created Date: 2010-05-28 Completed Date: 2010-07-21 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: United States |
Other Details:
|
Languages: eng Pagination: 2761-7 Citation Subset: IM |
Affiliation:
|
Haematology Department, Centre for Cancer Biology, SA Pathology (IMVS Campus), University of Adelaide, Frome Road, Adelaide, Australia. deb.white@imvs.sa.gov.au |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Analysis of Variance Antineoplastic Agents / administration & dosage, adverse effects Disease-Free Survival Dose-Response Relationship, Drug Drug Administration Schedule Female Follow-Up Studies Gene Expression Regulation, Leukemic / drug effects* Humans Kaplan-Meiers Estimate Leukemia, Myeloid, Chronic-Phase / drug therapy*, genetics*, mortality Male Maximum Tolerated Dose Middle Aged Organic Cation Transporter 1 / genetics* Piperazines / administration & dosage*, adverse effects Predictive Value of Tests Probability Pyrimidines / administration & dosage*, adverse effects RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction Risk Assessment Survival Analysis Time Factors Treatment Outcome |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Organic Cation Transporter 1; 0/Piperazines; 0/Pyrimidines; 0/RNA, Messenger; 152459-95-5/imatinib |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Phase II Parallel Group Study Showing Comparable Efficacy Between Premenopausal Metastatic Breast Ca...
Next Document: Oral Clofarabine in the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome.