ISOCHROMOSOME 17Q, UNBALANCED TRANSLOCATIONS AND 8Q GAIN REPRESENT ADVERSE PROGNOSTIC FACTORS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WITH 17P DELETION. A GFCH STUDY
(Abstract release date: 05/18/17)
EHA Library. Chapiro E. 05/18/17; 180777; E1001
Elise Chapiro
Contributions
Contributions
Abstract
Abstract: E1001
Type: Eposter Presentation
Background
Chromosomal abnormalities are present in about 80% of CLL. Among them, the loss of the short arm of the chromosome 17 (17p-), uncommon at diagnosis (<10%), is frequent in relapsed or refractory patients (up to 50%) and is associated with short survival. Loss of 17p results from various chromosomal abnormalities, including unbalanced translocations, deletions, rings or isochromosomes. All these aberrations lead to the loss of one copy of the TP53 gene, the remaining allele being generally mutated. In addition, 17p- is frequently accompanied by genomic complexity. Patients with 17p- typically progress quickly and are refractory to most conventional therapies.
Aims
We evaluated if the type of chromosomal abnormality leading to 17p- and the additional aberrations could influence the prognosis.
Methods
We collected data from a multicentric and retrospective cohort of 195 CLL patients harboring a TP53 deletion detected by FISH, with an informative conventional karyotype (K). All the K were reviewed by the members of the Groupe Francophone de Cytogénétique Hématologique. Overall survival (OS) and time to first treatment (TTFT) were calculated from diagnosis to death or first-line treatment, respectively, or last follow-up. The log-rank test was used to compare Kaplan-Meier curves. Cox regression models were used for multivariate analyses.
Results
The ratio H/F was 1.9. At diagnosis of CLL, the median age was 63 years [33-88], 59% were Binet stage A, 28% B, 12% C. IGHV genes were unmutated in 38/47 (81%) patients tested. The median follow-up was 70 months [0-401]. The majority of the patients was treated (87%), with a median TTFT of 13 months and a median of 2 lines of treatment [1-10]. In 28/124(23%) cases, the 17p- was not present at diagnosis and occurred after the first therapy, with a median time of 77.5 months [22-291] from the diagnosis. Karyotype was complex in 141/195(72%) patients, and monosomal in 90/195 (46%). The 17p- was the sole abnormality detected by K in 28/195(14%) cases.
A total of 240 17p abnormalities were found in the 195 patients. In the majority of cases, loss of 17p was the consequence of an unbalanced translocation (n=167/240, 70%), with various chromosome partners, the most frequent being the recurrent der/dic(17;18)(q10;q10) (n=32, 13%), followed by translocations involving chromosomes 8, 13, 14, 21, 15. Unbalanced translocations involving 17p and chromosome 8 (n=26, 11%), lead either to del8p (n=17), gain8q (n=6), or del8q (n=3). The other 17p abnormalities were: deletion 17p (n=45, 19%), monosomy 17 (n=15, 6%), isochromosome 17q [i(17q)] (n=9, 4%) and ring of chromosome 17 (n=4, 1%). Among the additional abnormalities accompanying the 17p-, unbalanced translocations were found in 121/195(63%) of patients. Combining FISH and K, del13q was detected in 71/118(60%) of cases, del8p in 40/189(21%), tri12 in 30/195(15%), gain8q in 13/105(12%), and del11q in 20/161(12%).
By univariate analysis, the paramaters which were associated with significantly shorter OS were: age >65 years, stage B/C, unmutated IGHV, i(17q) (69 months vs. 179, p=.0375), the presence of unbalanced translocations in addition to 17p- (153 vs. 223 months, p=.03), and gain8q (74 vs. 123 months, p=.0014). Monosomy 17, a total number of abnormalities >6 and gain8q predicted a shorter TTFT. By multivariate analysis, age >65 years, stage B/C and gain8q remained significant for OS.
Conclusion
Among the high risk group of 17p- CLL, i(17q) confers a shorter OS than the other 17p abnormalities. In addition, the gain8q aggravates the outcome as well as the presence of additional unbalanced translocations. These results confirm that patients with 17p- CLL have a variable clinical course and highlight the relevance of conventional karyotyping to identify the alterations that modulate the prognosis within these patients.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Chronic Lymphocytic Leukemia, prognosis, Cytogenetic abnormalities
Abstract: E1001
Type: Eposter Presentation
Background
Chromosomal abnormalities are present in about 80% of CLL. Among them, the loss of the short arm of the chromosome 17 (17p-), uncommon at diagnosis (<10%), is frequent in relapsed or refractory patients (up to 50%) and is associated with short survival. Loss of 17p results from various chromosomal abnormalities, including unbalanced translocations, deletions, rings or isochromosomes. All these aberrations lead to the loss of one copy of the TP53 gene, the remaining allele being generally mutated. In addition, 17p- is frequently accompanied by genomic complexity. Patients with 17p- typically progress quickly and are refractory to most conventional therapies.
Aims
We evaluated if the type of chromosomal abnormality leading to 17p- and the additional aberrations could influence the prognosis.
Methods
We collected data from a multicentric and retrospective cohort of 195 CLL patients harboring a TP53 deletion detected by FISH, with an informative conventional karyotype (K). All the K were reviewed by the members of the Groupe Francophone de Cytogénétique Hématologique. Overall survival (OS) and time to first treatment (TTFT) were calculated from diagnosis to death or first-line treatment, respectively, or last follow-up. The log-rank test was used to compare Kaplan-Meier curves. Cox regression models were used for multivariate analyses.
Results
The ratio H/F was 1.9. At diagnosis of CLL, the median age was 63 years [33-88], 59% were Binet stage A, 28% B, 12% C. IGHV genes were unmutated in 38/47 (81%) patients tested. The median follow-up was 70 months [0-401]. The majority of the patients was treated (87%), with a median TTFT of 13 months and a median of 2 lines of treatment [1-10]. In 28/124(23%) cases, the 17p- was not present at diagnosis and occurred after the first therapy, with a median time of 77.5 months [22-291] from the diagnosis. Karyotype was complex in 141/195(72%) patients, and monosomal in 90/195 (46%). The 17p- was the sole abnormality detected by K in 28/195(14%) cases.
A total of 240 17p abnormalities were found in the 195 patients. In the majority of cases, loss of 17p was the consequence of an unbalanced translocation (n=167/240, 70%), with various chromosome partners, the most frequent being the recurrent der/dic(17;18)(q10;q10) (n=32, 13%), followed by translocations involving chromosomes 8, 13, 14, 21, 15. Unbalanced translocations involving 17p and chromosome 8 (n=26, 11%), lead either to del8p (n=17), gain8q (n=6), or del8q (n=3). The other 17p abnormalities were: deletion 17p (n=45, 19%), monosomy 17 (n=15, 6%), isochromosome 17q [i(17q)] (n=9, 4%) and ring of chromosome 17 (n=4, 1%). Among the additional abnormalities accompanying the 17p-, unbalanced translocations were found in 121/195(63%) of patients. Combining FISH and K, del13q was detected in 71/118(60%) of cases, del8p in 40/189(21%), tri12 in 30/195(15%), gain8q in 13/105(12%), and del11q in 20/161(12%).
By univariate analysis, the paramaters which were associated with significantly shorter OS were: age >65 years, stage B/C, unmutated IGHV, i(17q) (69 months vs. 179, p=.0375), the presence of unbalanced translocations in addition to 17p- (153 vs. 223 months, p=.03), and gain8q (74 vs. 123 months, p=.0014). Monosomy 17, a total number of abnormalities >6 and gain8q predicted a shorter TTFT. By multivariate analysis, age >65 years, stage B/C and gain8q remained significant for OS.
Conclusion
Among the high risk group of 17p- CLL, i(17q) confers a shorter OS than the other 17p abnormalities. In addition, the gain8q aggravates the outcome as well as the presence of additional unbalanced translocations. These results confirm that patients with 17p- CLL have a variable clinical course and highlight the relevance of conventional karyotyping to identify the alterations that modulate the prognosis within these patients.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Chronic Lymphocytic Leukemia, prognosis, Cytogenetic abnormalities
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