BCL6 ABNORMALITIES ON FLUORESCENCE IN SITU HYBRIDIZATION ARE ASSOCIATED WITH EARLY AGE AT DIAGNOSIS, KARYOTYPIC COMPLEXITY, AND AGGRESSIVE DISEASE IN CHRONIC LYMPHOCYTIC LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Eulitt P. 06/09/16; 132605; E1056
Dr. Patrick Eulitt
Contributions
Contributions
Abstract
Abstract: E1056
Type: Eposter Presentation
Background
The clinical course of CLL is variable but can be predicted in part by recurrent cytogenetic abnormalities. BCL6 functions as a transcriptional repressor during germinal center formation, and alteration of 3q27 has been well characterized in some B cell malignancies. However, the incidence and significance of BCL6 abnormalities in CLL is unknown.
Aims
We aimed to determine the incidence and clinical significance of BCL6 abnormalities in CLL by analyzing a large database of CLL patients. We then aimed to analyze subsets of patients enrolled in clinical trials to determine the signficance of primary BCL6 abnormalities compared to acquired BCL6 abnormalities.
Methods
Between 10/2007 and 6/2014, 1811 patients (pts) with CLL at our institution underwent FISH which included a probe for 3q27. Clinical and molecular data were reviewed for pts with rearrangements or extra copies of BCL6. Data were also obtained from pts participating in 4 sequential clinical trials of ibrutinib, and characteristics of pts with and without pre-treatment BCL6 abnormalities were compared.
Results
152 pts (8.4%) were found to have an abnormality of BCL6 at any time during their clinical course. Clinical and cytogenetic characteristics are summarized below. BCL6 abnormalities were present prior to first therapy in 28 pts, suggesting a primary abnormality. These pts had an early age at diagnosis (62.5 years), short time from diagnosis to first treatment (median 23.6 months), and relatively low 5-year survival (estimated at 62.9%). Pts with BCL6 abnormalities were likely to have complex karyotype and other high risk abnormalities including MYC rearrangement/copy gains and del(17p). Comparing pts with and without BCL6 abnormalities undergoing similar therapy, those with BCL6 abnormalities were more likely to have complex karyotype (p = 0.0007), MYC abnormalities (p < 0.0001), and del(17p) (p < 0.0001).
Conclusion
BCL6 abnormalities are associated with other high risk markers in CLL, and these pts have early age at diagnosis, short time to first therapy, and relatively short survival. These data suggest that BCL6 FISH abnormalities may be an important biomarker in CLL. Work to further characterize the biologic basis for these findings is ongoing.
Session topic: E-poster
Keyword(s): BCL6, Chronic lymphocytic leukemia, Cytogenetic abnormalities, Prognostic factor
Type: Eposter Presentation
Background
The clinical course of CLL is variable but can be predicted in part by recurrent cytogenetic abnormalities. BCL6 functions as a transcriptional repressor during germinal center formation, and alteration of 3q27 has been well characterized in some B cell malignancies. However, the incidence and significance of BCL6 abnormalities in CLL is unknown.
Aims
We aimed to determine the incidence and clinical significance of BCL6 abnormalities in CLL by analyzing a large database of CLL patients. We then aimed to analyze subsets of patients enrolled in clinical trials to determine the signficance of primary BCL6 abnormalities compared to acquired BCL6 abnormalities.
Methods
Between 10/2007 and 6/2014, 1811 patients (pts) with CLL at our institution underwent FISH which included a probe for 3q27. Clinical and molecular data were reviewed for pts with rearrangements or extra copies of BCL6. Data were also obtained from pts participating in 4 sequential clinical trials of ibrutinib, and characteristics of pts with and without pre-treatment BCL6 abnormalities were compared.
Results
152 pts (8.4%) were found to have an abnormality of BCL6 at any time during their clinical course. Clinical and cytogenetic characteristics are summarized below. BCL6 abnormalities were present prior to first therapy in 28 pts, suggesting a primary abnormality. These pts had an early age at diagnosis (62.5 years), short time from diagnosis to first treatment (median 23.6 months), and relatively low 5-year survival (estimated at 62.9%). Pts with BCL6 abnormalities were likely to have complex karyotype and other high risk abnormalities including MYC rearrangement/copy gains and del(17p). Comparing pts with and without BCL6 abnormalities undergoing similar therapy, those with BCL6 abnormalities were more likely to have complex karyotype (p = 0.0007), MYC abnormalities (p < 0.0001), and del(17p) (p < 0.0001).
Conclusion
BCL6 abnormalities are associated with other high risk markers in CLL, and these pts have early age at diagnosis, short time to first therapy, and relatively short survival. These data suggest that BCL6 FISH abnormalities may be an important biomarker in CLL. Work to further characterize the biologic basis for these findings is ongoing.
Session topic: E-poster
Keyword(s): BCL6, Chronic lymphocytic leukemia, Cytogenetic abnormalities, Prognostic factor
Abstract: E1056
Type: Eposter Presentation
Background
The clinical course of CLL is variable but can be predicted in part by recurrent cytogenetic abnormalities. BCL6 functions as a transcriptional repressor during germinal center formation, and alteration of 3q27 has been well characterized in some B cell malignancies. However, the incidence and significance of BCL6 abnormalities in CLL is unknown.
Aims
We aimed to determine the incidence and clinical significance of BCL6 abnormalities in CLL by analyzing a large database of CLL patients. We then aimed to analyze subsets of patients enrolled in clinical trials to determine the signficance of primary BCL6 abnormalities compared to acquired BCL6 abnormalities.
Methods
Between 10/2007 and 6/2014, 1811 patients (pts) with CLL at our institution underwent FISH which included a probe for 3q27. Clinical and molecular data were reviewed for pts with rearrangements or extra copies of BCL6. Data were also obtained from pts participating in 4 sequential clinical trials of ibrutinib, and characteristics of pts with and without pre-treatment BCL6 abnormalities were compared.
Results
152 pts (8.4%) were found to have an abnormality of BCL6 at any time during their clinical course. Clinical and cytogenetic characteristics are summarized below. BCL6 abnormalities were present prior to first therapy in 28 pts, suggesting a primary abnormality. These pts had an early age at diagnosis (62.5 years), short time from diagnosis to first treatment (median 23.6 months), and relatively low 5-year survival (estimated at 62.9%). Pts with BCL6 abnormalities were likely to have complex karyotype and other high risk abnormalities including MYC rearrangement/copy gains and del(17p). Comparing pts with and without BCL6 abnormalities undergoing similar therapy, those with BCL6 abnormalities were more likely to have complex karyotype (p = 0.0007), MYC abnormalities (p < 0.0001), and del(17p) (p < 0.0001).
Conclusion
BCL6 abnormalities are associated with other high risk markers in CLL, and these pts have early age at diagnosis, short time to first therapy, and relatively short survival. These data suggest that BCL6 FISH abnormalities may be an important biomarker in CLL. Work to further characterize the biologic basis for these findings is ongoing.
Session topic: E-poster
Keyword(s): BCL6, Chronic lymphocytic leukemia, Cytogenetic abnormalities, Prognostic factor
Type: Eposter Presentation
Background
The clinical course of CLL is variable but can be predicted in part by recurrent cytogenetic abnormalities. BCL6 functions as a transcriptional repressor during germinal center formation, and alteration of 3q27 has been well characterized in some B cell malignancies. However, the incidence and significance of BCL6 abnormalities in CLL is unknown.
Aims
We aimed to determine the incidence and clinical significance of BCL6 abnormalities in CLL by analyzing a large database of CLL patients. We then aimed to analyze subsets of patients enrolled in clinical trials to determine the signficance of primary BCL6 abnormalities compared to acquired BCL6 abnormalities.
Methods
Between 10/2007 and 6/2014, 1811 patients (pts) with CLL at our institution underwent FISH which included a probe for 3q27. Clinical and molecular data were reviewed for pts with rearrangements or extra copies of BCL6. Data were also obtained from pts participating in 4 sequential clinical trials of ibrutinib, and characteristics of pts with and without pre-treatment BCL6 abnormalities were compared.
Results
152 pts (8.4%) were found to have an abnormality of BCL6 at any time during their clinical course. Clinical and cytogenetic characteristics are summarized below. BCL6 abnormalities were present prior to first therapy in 28 pts, suggesting a primary abnormality. These pts had an early age at diagnosis (62.5 years), short time from diagnosis to first treatment (median 23.6 months), and relatively low 5-year survival (estimated at 62.9%). Pts with BCL6 abnormalities were likely to have complex karyotype and other high risk abnormalities including MYC rearrangement/copy gains and del(17p). Comparing pts with and without BCL6 abnormalities undergoing similar therapy, those with BCL6 abnormalities were more likely to have complex karyotype (p = 0.0007), MYC abnormalities (p < 0.0001), and del(17p) (p < 0.0001).
Conclusion
BCL6 abnormalities are associated with other high risk markers in CLL, and these pts have early age at diagnosis, short time to first therapy, and relatively short survival. These data suggest that BCL6 FISH abnormalities may be an important biomarker in CLL. Work to further characterize the biologic basis for these findings is ongoing.
Session topic: E-poster
Keyword(s): BCL6, Chronic lymphocytic leukemia, Cytogenetic abnormalities, Prognostic factor
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