The University of Southampton
University of Southampton Institutional Repository

The outcome of chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with

The outcome of chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with
The outcome of chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with
IGHV gene mutational status has prognostic significance in chronic lymphocytic leukaemia (CLL) but the percentage of mutations that correlates best with clinical outcome remains controversial. We initially studied 558 patients from diagnosis and found significant differences in median time to first treatment (TTFT) among Stage A patients and in overall survival (OS) for the whole cohort, between cases with <97% and 97-98·99% identity and between cases with 97-98·99% and ?99% identity, when cases from the IGHV3-21 Stereotype Subset #2 were excluded. A significant difference in progression-free survival (PFS) and OS between those with <97% and 97-98·99% identity, but not between those with 97-98·99% and ?99% identity was also observed in a validation cohort comprising 460 patients in the UK CLL4 trial. Cox Regression analyses in the Stage A cohort revealed that a model which incorporated <97%, 97-98·99% and ?99% identity as subgroups, was a better predictor of TTFT in CLL than using the 98% cut-off. Multivariate analysis selected the three mutational subgroups as independent predictors of TTFT in Stage A patients, and of OS in the diagnostic cohort. This study highlights that cases with 97% identity should not be considered to have the same prognosis as other cases with mutated IGHV genes defined as <98% identity to germline
chronic lymphocytic leukaemia, v-genes, mutation analysis, prognostic factors, ighv
0007-1048
1-10
Davis, Zadie
ea848a46-b564-448f-b77f-840d86b3cbd9
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Parker, Anton
31389ac7-a2e6-4db1-989d-9551580fae35
Gardiner, Anne
31ec2c9a-dccb-468f-83d1-d4f03ac88f33
Thomas, Peter
67958748-7e3a-48e9-940d-b2b241686d70
Catovsky, Daniel
0c2a5c78-d841-456e-88c7-581850d4e80a
Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Oscier, David
2e7f0cc1-93e2-441e-857d-7314efae08ec
Davis, Zadie
ea848a46-b564-448f-b77f-840d86b3cbd9
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Parker, Anton
31389ac7-a2e6-4db1-989d-9551580fae35
Gardiner, Anne
31ec2c9a-dccb-468f-83d1-d4f03ac88f33
Thomas, Peter
67958748-7e3a-48e9-940d-b2b241686d70
Catovsky, Daniel
0c2a5c78-d841-456e-88c7-581850d4e80a
Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Oscier, David
2e7f0cc1-93e2-441e-857d-7314efae08ec

Davis, Zadie, Forconi, Francesco, Parker, Anton, Gardiner, Anne, Thomas, Peter, Catovsky, Daniel, Rose-Zerilli, Matthew, Strefford, Jonathan and Oscier, David (2016) The outcome of chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with. British Journal of Haematology, 1-10. (doi:10.1111/bjh.13940). (PMID:26846718)

Record type: Article

Abstract

IGHV gene mutational status has prognostic significance in chronic lymphocytic leukaemia (CLL) but the percentage of mutations that correlates best with clinical outcome remains controversial. We initially studied 558 patients from diagnosis and found significant differences in median time to first treatment (TTFT) among Stage A patients and in overall survival (OS) for the whole cohort, between cases with <97% and 97-98·99% identity and between cases with 97-98·99% and ?99% identity, when cases from the IGHV3-21 Stereotype Subset #2 were excluded. A significant difference in progression-free survival (PFS) and OS between those with <97% and 97-98·99% identity, but not between those with 97-98·99% and ?99% identity was also observed in a validation cohort comprising 460 patients in the UK CLL4 trial. Cox Regression analyses in the Stage A cohort revealed that a model which incorporated <97%, 97-98·99% and ?99% identity as subgroups, was a better predictor of TTFT in CLL than using the 98% cut-off. Multivariate analysis selected the three mutational subgroups as independent predictors of TTFT in Stage A patients, and of OS in the diagnostic cohort. This study highlights that cases with 97% identity should not be considered to have the same prognosis as other cases with mutated IGHV genes defined as <98% identity to germline

Text
__soton.ac.uk_ude_PersonalFiles_Users_jcs_mydocuments_PDF Archive_My Papers_2016_Davis_Strefford_IGH%_British_Journal_of_Haematology.pdf - Version of Record
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 18 November 2015
e-pub ahead of print date: 6 February 2016
Keywords: chronic lymphocytic leukaemia, v-genes, mutation analysis, prognostic factors, ighv
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 387167
URI: http://eprints.soton.ac.uk/id/eprint/387167
ISSN: 0007-1048
PURE UUID: 683002d1-75e0-4d1f-a2a0-e5a30059a32c
ORCID for Francesco Forconi: ORCID iD orcid.org/0000-0002-2211-1831
ORCID for Matthew Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for Jonathan Strefford: ORCID iD orcid.org/0000-0002-0972-2881

Catalogue record

Date deposited: 16 Feb 2016 12:14
Last modified: 15 Mar 2024 03:41

Export record

Altmetrics

Contributors

Author: Zadie Davis
Author: Anton Parker
Author: Anne Gardiner
Author: Peter Thomas
Author: Daniel Catovsky
Author: David Oscier

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×