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
1-10
Davis, Zadie
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Forconi, Francesco
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Parker, Anton
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Gardiner, Anne
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Thomas, Peter
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Catovsky, Daniel
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Rose-Zerilli, Matthew
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Strefford, Jonathan
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Oscier, David
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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
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Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Oscier, David
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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, .
(doi:10.1111/bjh.13940).
(PMID:26846718)
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
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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
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Date deposited: 16 Feb 2016 12:14
Last modified: 15 Mar 2024 03:41
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Author:
Zadie Davis
Author:
Anton Parker
Author:
Anne Gardiner
Author:
Peter Thomas
Author:
Daniel Catovsky
Author:
David Oscier
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