THE PROGNOSTIC SIGNIFICANCE OF PROLYMPHOCYTES IN CLL AND CORRELATION WITH MOLECULAR MARKERS IN THE LRF CLL4 TRIAL
(Abstract release date: 05/19/16)
EHA Library. Catovsky D. 06/09/16; 132610; E1061
Prof. Dr. Daniel Catovsky
Contributions
Contributions
Abstract
Abstract: E1061
Type: Eposter Presentation
Background
An increase in the percentage and number of circulating prolymphocytes in CLL has been associated with strong expression of surface immunoglobulin (SmIg), trisomy 12 and a poor outcome (Melo et al, Br J Haematol 1986;63:377 & 1987;65:23; Que et al, Blood 1993;82:571).
Aims
This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in patients entered into the randomised UK LRF CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers.
Methods
777 previously untreated patients were randomised between 1999 and 2004 to receive either chlorambucil or fludarabine, alone or in combination with cyclophosphamide. Median follow-up for overall survival (OS) was 11.8 (range 10.2 – 15.9) years. The proportion of prolymphocytes was assessed at trial entry in 508 patients.
Results
270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had =>15% prolymphocytes. We confirmed the association of increased prolymphocytes (=>10%) with strong SmIg expression and trisomy 12. In multivariate analysis =>10% prolymphocytes was independently associated with NOTCH1 mutations, absence of 13q deletion, high CD38 expression and unmutated IGHV genes:
Increased prolymphocytes (=>10%) were associated with a shorter progression-free survival (HR 1.50 [95%CI: 1.16-1.93], p=0.002) and OS (HR 1.99 [95%CI 1.53-2.59], p<0.0001; Figure 1). An absolute prolymphocyte count >=15x109/L was also associated with longer OS (HR 1.53 [95%CI 1.15-2.04], p=0.004). =>10% prolymphocytes was an independent predictor of OS when the multivariate model included the significant variables age, disease stage, 11q and 13q deletion and TP53 del/mut together with any one of the following, each included separately: IGHV mutational status, B2M, CD38, Zap70 or CLLU1 expression, mutations on NOTCH1 or SF3B1, or telomere length. When all the significant variables were included together, % prolymphocytes was not an independent predictor of OS. Deaths due to Richter’s syndrome were more common amongst patients who had =>10% prolymphocytes at trial entry (9/71, 13%) vs those with <10% prolymphocytes (8/437, 2%; p<0.0001).
Conclusion
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 a further evaluation of clinical and laboratory features of progressive disease.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Molecular markers, Prognostic factor
Type: Eposter Presentation
Background
An increase in the percentage and number of circulating prolymphocytes in CLL has been associated with strong expression of surface immunoglobulin (SmIg), trisomy 12 and a poor outcome (Melo et al, Br J Haematol 1986;63:377 & 1987;65:23; Que et al, Blood 1993;82:571).
Aims
This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in patients entered into the randomised UK LRF CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers.
Methods
777 previously untreated patients were randomised between 1999 and 2004 to receive either chlorambucil or fludarabine, alone or in combination with cyclophosphamide. Median follow-up for overall survival (OS) was 11.8 (range 10.2 – 15.9) years. The proportion of prolymphocytes was assessed at trial entry in 508 patients.
Results
270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had =>15% prolymphocytes. We confirmed the association of increased prolymphocytes (=>10%) with strong SmIg expression and trisomy 12. In multivariate analysis =>10% prolymphocytes was independently associated with NOTCH1 mutations, absence of 13q deletion, high CD38 expression and unmutated IGHV genes:
| Variable | Odds ratio | 95% Confidence Limits | p | |
| NOTCH1 mutation | 3.88 | 1.46 | 10.30 | 0.006 |
| Absence of 13q deletion | 4.41 | 1.82 | 10.69 | 0.001 |
| Positive CD38 expression | 6.48 | 1.44 | 29.25 | 0.02 |
| Unmutated IGHV genes | 5.02 | 1.39 | 18.17 | 0.01 |
Conclusion
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 a further evaluation of clinical and laboratory features of progressive disease.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Molecular markers, Prognostic factor
Abstract: E1061
Type: Eposter Presentation
Background
An increase in the percentage and number of circulating prolymphocytes in CLL has been associated with strong expression of surface immunoglobulin (SmIg), trisomy 12 and a poor outcome (Melo et al, Br J Haematol 1986;63:377 & 1987;65:23; Que et al, Blood 1993;82:571).
Aims
This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in patients entered into the randomised UK LRF CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers.
Methods
777 previously untreated patients were randomised between 1999 and 2004 to receive either chlorambucil or fludarabine, alone or in combination with cyclophosphamide. Median follow-up for overall survival (OS) was 11.8 (range 10.2 – 15.9) years. The proportion of prolymphocytes was assessed at trial entry in 508 patients.
Results
270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had =>15% prolymphocytes. We confirmed the association of increased prolymphocytes (=>10%) with strong SmIg expression and trisomy 12. In multivariate analysis =>10% prolymphocytes was independently associated with NOTCH1 mutations, absence of 13q deletion, high CD38 expression and unmutated IGHV genes:
Increased prolymphocytes (=>10%) were associated with a shorter progression-free survival (HR 1.50 [95%CI: 1.16-1.93], p=0.002) and OS (HR 1.99 [95%CI 1.53-2.59], p<0.0001; Figure 1). An absolute prolymphocyte count >=15x109/L was also associated with longer OS (HR 1.53 [95%CI 1.15-2.04], p=0.004). =>10% prolymphocytes was an independent predictor of OS when the multivariate model included the significant variables age, disease stage, 11q and 13q deletion and TP53 del/mut together with any one of the following, each included separately: IGHV mutational status, B2M, CD38, Zap70 or CLLU1 expression, mutations on NOTCH1 or SF3B1, or telomere length. When all the significant variables were included together, % prolymphocytes was not an independent predictor of OS. Deaths due to Richter’s syndrome were more common amongst patients who had =>10% prolymphocytes at trial entry (9/71, 13%) vs those with <10% prolymphocytes (8/437, 2%; p<0.0001).
Conclusion
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 a further evaluation of clinical and laboratory features of progressive disease.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Molecular markers, Prognostic factor
Type: Eposter Presentation
Background
An increase in the percentage and number of circulating prolymphocytes in CLL has been associated with strong expression of surface immunoglobulin (SmIg), trisomy 12 and a poor outcome (Melo et al, Br J Haematol 1986;63:377 & 1987;65:23; Que et al, Blood 1993;82:571).
Aims
This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in patients entered into the randomised UK LRF CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers.
Methods
777 previously untreated patients were randomised between 1999 and 2004 to receive either chlorambucil or fludarabine, alone or in combination with cyclophosphamide. Median follow-up for overall survival (OS) was 11.8 (range 10.2 – 15.9) years. The proportion of prolymphocytes was assessed at trial entry in 508 patients.
Results
270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had =>15% prolymphocytes. We confirmed the association of increased prolymphocytes (=>10%) with strong SmIg expression and trisomy 12. In multivariate analysis =>10% prolymphocytes was independently associated with NOTCH1 mutations, absence of 13q deletion, high CD38 expression and unmutated IGHV genes:
| Variable | Odds ratio | 95% Confidence Limits | p | |
| NOTCH1 mutation | 3.88 | 1.46 | 10.30 | 0.006 |
| Absence of 13q deletion | 4.41 | 1.82 | 10.69 | 0.001 |
| Positive CD38 expression | 6.48 | 1.44 | 29.25 | 0.02 |
| Unmutated IGHV genes | 5.02 | 1.39 | 18.17 | 0.01 |
Conclusion
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 a further evaluation of clinical and laboratory features of progressive disease.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Molecular markers, Prognostic factor
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