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The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial

The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial
The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial
Historically, an increase in the percentage and number of circulating prolymphocytes in chronic lymphocytic leukaemia (CLL) has been associated with strong expression of surface immunoglobulin, trisomy 12 and a poor outcome. This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in 508 patients at entry into the randomized UK Leukaemia Research Fund CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers. 270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had ?15% prolymphocytes. We show that a higher proportion of prolymphocytes (?10%) was independently associated with NOTCH1 mutations (P = 0·006), absence of 13q deletion (P = 0·001), high CD38 expression (P = 0·02) and unmutated IGHV genes (P = 0·01). Deaths due to Richter syndrome were significantly more common amongst patients who had ?10% vs <10% prolymphocytes (13% vs 2%) respectively (P < 0·0001). ?10% prolymphocytes was also associated with a shorter progression-free survival (Hazard ratio [HR] 1·50 [95% confidence interval [CI]: 1·16-1·93], P = 0·002) and overall survival (HR 1·99 [95% CI: 1·53-2·59], P < 0·0001). Our data support the routine examination of blood films in CLL and suggest that a finding of an increased proportion of prolymphocytes may be a trigger for further evaluation of clinical and laboratory features of progressive disease.
0007-1048
1-9
Oscier, David
2e7f0cc1-93e2-441e-857d-7314efae08ec
Else, Monica
3d354259-1969-4d47-9eea-5b95daaf2089
Matutes, Estella
3da6561d-9c65-48b3-9273-db3c93f77a80
Morilla, Ricardo
97c98609-2447-40d0-9f44-203574ac9e1d
Strefford, Jonathan C.
3782b392-f080-42bf-bdca-8aa5d6ca532f
Catovsky, Daniel
0c2a5c78-d841-456e-88c7-581850d4e80a
Oscier, David
2e7f0cc1-93e2-441e-857d-7314efae08ec
Else, Monica
3d354259-1969-4d47-9eea-5b95daaf2089
Matutes, Estella
3da6561d-9c65-48b3-9273-db3c93f77a80
Morilla, Ricardo
97c98609-2447-40d0-9f44-203574ac9e1d
Strefford, Jonathan C.
3782b392-f080-42bf-bdca-8aa5d6ca532f
Catovsky, Daniel
0c2a5c78-d841-456e-88c7-581850d4e80a

Oscier, David, Else, Monica, Matutes, Estella, Morilla, Ricardo, Strefford, Jonathan C. and Catovsky, Daniel (2016) The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial. British Journal of Haematology, 1-9. (doi:10.1111/bjh.14132). (PMID:27151266)

Record type: Article

Abstract

Historically, an increase in the percentage and number of circulating prolymphocytes in chronic lymphocytic leukaemia (CLL) has been associated with strong expression of surface immunoglobulin, trisomy 12 and a poor outcome. This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in 508 patients at entry into the randomized UK Leukaemia Research Fund CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers. 270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had ?15% prolymphocytes. We show that a higher proportion of prolymphocytes (?10%) was independently associated with NOTCH1 mutations (P = 0·006), absence of 13q deletion (P = 0·001), high CD38 expression (P = 0·02) and unmutated IGHV genes (P = 0·01). Deaths due to Richter syndrome were significantly more common amongst patients who had ?10% vs <10% prolymphocytes (13% vs 2%) respectively (P < 0·0001). ?10% prolymphocytes was also associated with a shorter progression-free survival (Hazard ratio [HR] 1·50 [95% confidence interval [CI]: 1·16-1·93], P = 0·002) and overall survival (HR 1·99 [95% CI: 1·53-2·59], P < 0·0001). Our data support the routine examination of blood films in CLL and suggest that a finding of an increased proportion of prolymphocytes may be a trigger for further evaluation of clinical and laboratory features of progressive disease.

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Accepted/In Press date: 20 March 2016
e-pub ahead of print date: 6 May 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 394138
URI: http://eprints.soton.ac.uk/id/eprint/394138
ISSN: 0007-1048
PURE UUID: 42aa068c-872e-461e-8ede-db49551cd97d
ORCID for Jonathan C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 12 May 2016 08:52
Last modified: 15 Mar 2024 03:20

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Contributors

Author: David Oscier
Author: Monica Else
Author: Estella Matutes
Author: Ricardo Morilla
Author: Daniel Catovsky

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