Telomere length predicts for outcome to FCR chemotherapy in CLL
We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could pred...
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ftpubmed:oai:pubmedcentral.nih.gov:6756045 2023-05-15T15:08:14+02:00 Telomere length predicts for outcome to FCR chemotherapy in CLL Norris, Kevin Hillmen, Peter Rawstron, Andrew Hills, Robert Baird, Duncan M. Fegan, Christopher D. Pepper, Chris 2019-01-30 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756045/ http://www.ncbi.nlm.nih.gov/pubmed/30700843 https://doi.org/10.1038/s41375-019-0389-9 en eng Nature Publishing Group UK http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756045/ http://www.ncbi.nlm.nih.gov/pubmed/30700843 http://dx.doi.org/10.1038/s41375-019-0389-9 © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. CC-BY Article Text 2019 ftpubmed https://doi.org/10.1038/s41375-019-0389-9 2019-09-29T00:24:29Z We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could predict for outcome to fludarabine, cyclophosphamide, rituximab (FCR)-based treatment using samples collected from two concurrent phase II studies, ARCTIC and ADMIRE (n = 260). In univariate analysis, patients with TL-IFR had reduced progression-free survival (PFS) (P < 0.0001; HR = 2.17) and shorter overall survival (OS) (P = 0.0002; HR = 2.44). Bifurcation of the IGHV-mutated and unmutated subsets according to telomere length revealed that patients with TL-IFR in each subset had shorter PFS (HR = 4.35 and HR = 1.48, respectively) and shorter OS (HR = 3.81 and HR = 2.18, respectively). In addition, the OS of the TL-OFR and TL-IFR subsets were not significantly altered by IGHV mutation status (P = 0.61; HR = 1.24 and P = 0.41; HR = 1.47, respectively). In multivariate modeling, telomere length was the dominant co-variable for PFS (P = 0.0002; HR = 1.85) and OS (P = 0.05; HR = 1.61). Taken together, our data suggest that HT-STELA is a powerful predictor of outcome to FCR-based treatment and could be used to inform the design of future risk-adapted clinical trials. Text Arctic PubMed Central (PMC) Arctic Leukemia 33 8 1953 1963 |
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Article Norris, Kevin Hillmen, Peter Rawstron, Andrew Hills, Robert Baird, Duncan M. Fegan, Christopher D. Pepper, Chris Telomere length predicts for outcome to FCR chemotherapy in CLL |
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We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could predict for outcome to fludarabine, cyclophosphamide, rituximab (FCR)-based treatment using samples collected from two concurrent phase II studies, ARCTIC and ADMIRE (n = 260). In univariate analysis, patients with TL-IFR had reduced progression-free survival (PFS) (P < 0.0001; HR = 2.17) and shorter overall survival (OS) (P = 0.0002; HR = 2.44). Bifurcation of the IGHV-mutated and unmutated subsets according to telomere length revealed that patients with TL-IFR in each subset had shorter PFS (HR = 4.35 and HR = 1.48, respectively) and shorter OS (HR = 3.81 and HR = 2.18, respectively). In addition, the OS of the TL-OFR and TL-IFR subsets were not significantly altered by IGHV mutation status (P = 0.61; HR = 1.24 and P = 0.41; HR = 1.47, respectively). In multivariate modeling, telomere length was the dominant co-variable for PFS (P = 0.0002; HR = 1.85) and OS (P = 0.05; HR = 1.61). Taken together, our data suggest that HT-STELA is a powerful predictor of outcome to FCR-based treatment and could be used to inform the design of future risk-adapted clinical trials. |
format |
Text |
author |
Norris, Kevin Hillmen, Peter Rawstron, Andrew Hills, Robert Baird, Duncan M. Fegan, Christopher D. Pepper, Chris |
author_facet |
Norris, Kevin Hillmen, Peter Rawstron, Andrew Hills, Robert Baird, Duncan M. Fegan, Christopher D. Pepper, Chris |
author_sort |
Norris, Kevin |
title |
Telomere length predicts for outcome to FCR chemotherapy in CLL |
title_short |
Telomere length predicts for outcome to FCR chemotherapy in CLL |
title_full |
Telomere length predicts for outcome to FCR chemotherapy in CLL |
title_fullStr |
Telomere length predicts for outcome to FCR chemotherapy in CLL |
title_full_unstemmed |
Telomere length predicts for outcome to FCR chemotherapy in CLL |
title_sort |
telomere length predicts for outcome to fcr chemotherapy in cll |
publisher |
Nature Publishing Group UK |
publishDate |
2019 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756045/ http://www.ncbi.nlm.nih.gov/pubmed/30700843 https://doi.org/10.1038/s41375-019-0389-9 |
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Arctic |
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Arctic |
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Arctic |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756045/ http://www.ncbi.nlm.nih.gov/pubmed/30700843 http://dx.doi.org/10.1038/s41375-019-0389-9 |
op_rights |
© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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CC-BY |
op_doi |
https://doi.org/10.1038/s41375-019-0389-9 |
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Leukemia |
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1953 |
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1963 |
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