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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ftleedsuniv:oai:eprints.whiterose.ac.uk:157067 2023-05-15T15:06:59+02:00 Telomere length predicts for outcome to FCR chemotherapy in CLL Norris, K Hillmen, P Rawstron, A Hills, R Baird, DM Fegan, CD Pepper, C 2019-08 text https://eprints.whiterose.ac.uk/157067/ https://eprints.whiterose.ac.uk/157067/1/s41375-019-0389-9.pdf en eng Springer Nature https://eprints.whiterose.ac.uk/157067/1/s41375-019-0389-9.pdf Norris, K, Hillmen, P orcid.org/0000-0001-5617-4403 , Rawstron, A orcid.org/0000-0003-0798-9790 et al. (4 more authors) (2019) Telomere length predicts for outcome to FCR chemotherapy in CLL. Leukemia, 33 (8). pp. 1953-1963. ISSN 0887-6924 cc_by_4 CC-BY Article NonPeerReviewed 2019 ftleedsuniv 2023-01-30T22:27:00Z 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. Article in Journal/Newspaper Arctic White Rose Research Online (Universities of Leeds, Sheffield & York) Arctic |
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White Rose Research Online (Universities of Leeds, Sheffield & York) |
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English |
description |
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 |
Article in Journal/Newspaper |
author |
Norris, K Hillmen, P Rawstron, A Hills, R Baird, DM Fegan, CD Pepper, C |
spellingShingle |
Norris, K Hillmen, P Rawstron, A Hills, R Baird, DM Fegan, CD Pepper, C Telomere length predicts for outcome to FCR chemotherapy in CLL |
author_facet |
Norris, K Hillmen, P Rawstron, A Hills, R Baird, DM Fegan, CD Pepper, C |
author_sort |
Norris, K |
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 |
Springer Nature |
publishDate |
2019 |
url |
https://eprints.whiterose.ac.uk/157067/ https://eprints.whiterose.ac.uk/157067/1/s41375-019-0389-9.pdf |
geographic |
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geographic_facet |
Arctic |
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Arctic |
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op_relation |
https://eprints.whiterose.ac.uk/157067/1/s41375-019-0389-9.pdf Norris, K, Hillmen, P orcid.org/0000-0001-5617-4403 , Rawstron, A orcid.org/0000-0003-0798-9790 et al. (4 more authors) (2019) Telomere length predicts for outcome to FCR chemotherapy in CLL. Leukemia, 33 (8). pp. 1953-1963. ISSN 0887-6924 |
op_rights |
cc_by_4 |
op_rightsnorm |
CC-BY |
_version_ |
1766338572769558528 |