CHROMOSOMAL GAINS IN CHRONIC LYMPHOCYTIC LEUKEMIA: A RARE EVENT ASSOCIATED WITH A DISMAL PROGNOSIS
(Abstract release date: 05/19/16)
EHA Library. González-Gascón y Marín I. 06/09/16; 132595; E1046
Dr. Isabel González-Gascón y Marín
Contributions
Contributions
Abstract
Abstract: E1046
Type: Eposter Presentation
Background
Hyperdiploidy is a common cytogenetic alteration in some hematological diseases such as B acute lymphoblastic leukemia or multiple myeloma, with prognostic value. However, the presence of chromosomal gains other tan trisomy 12 (+12) in chronic lymphocytic leukemia (CLL) has scarcely been reported before.
Aims
The aim of this study was to analyze, by FISH, the frequency and prognostic implications of chromosomal gains in CLL.
Methods
A retrospective review of 1,359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution, between 2004 and 2012, was carried out. Chromosomal gains were considered when a gain of at least 3 out of the 5 FISH probes used (11q22/ATM, 12q13, 13q34, 14q34/IGH, and 17p13/TP53) was observed. In addition, Next Generation Sequencing analysis was carried out to investigate the mutational status of TP53 (exons 4–11) gene.
Results
8 cases with chromosomal gains were identified out of the 1,359 CLL patients (0.59%), referred for FISH studies. One case was excluded from the analysis due to inadequate follow-up. Five cases (cases nº 3-7) presented chromosomal gains at diagnosis; the other two (case nº 1 and 2) during disease evolution and after having received treatment with chlorambucil. Four patients (57%) were female, and the median age at diagnosis was 74 years (range 63-86). The median white blood cell count at the time of diagnosis was 16 x 109/L (range, 7-67). No significant anemia or thrombocytopenia were detected in any case at diagnosis. It is noteworthy that the immunophenotype of three out of the seven cases suggested the diagnosis of atypical CLL. Serum LDH and β2microglobulin levels at diagnosis were high in 57% (4/7) and 29% of the cases (2/7), respectively. Three out of seven (43%) patients presented with splenomegaly and hepatomegaly, and 29% with more than three enlarged lymph node regions. The presence of B symptoms was detected in 29% of the cases. Of note, at the time of diagnosis most cases were classified as early stages according to Binet classification (stage A 57%; stage B 29%; stage C 14%). IGHV mutation status was available in 57% of the cases being all of them classified as unmutated pattern. Besides chromosomal gains, additional chromosomal abnormalities were detected in 57% of the patients including: 17p- (2 cases), 11q- and IGH alteration (1 case), and 13q- and IGH deletion (1case). Detailed FISH results are shown in Table I. Only one patient (case nº 7) showed a missense TP53 mutation (c.613T>G; p.Y205D) with a mutational burden of 95%. This variation was previously described as a mutation in the COSMIC database (COSM43844). This TP53 mutated case did not show 17p deletion. Six patients (86%) required treatment during follow-up with a median TTFT of 1.4 months (CI95%, 0.8-1.9). Most treated patients (4/6, 66%) required two or more chemotherapy therapies (median 3, range: 1-4), due to refractoriness or relapse. Median duration of response to first line treatment was 7 months (0-36). With a median follow-up of 66 months (6-115), 5 patients have died due to: disease progression (3 cases), infection (1 case), and cardiovascular disease (1 case). Median OS from the time of diagnosis was 66 months (CI95%, 0-174), and from the time of chromosomal gains acquisition was 20 months (CI95%, 16-24).
Conclusion
Chromosomal gains are a rare event in CLL. Our results also suggest that the presence of chromosomal gains involves poor prognosis in these patients. This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI15/01471
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Chronic lymphocytic leukemia, FISH, Prognosis
Type: Eposter Presentation
Background
Hyperdiploidy is a common cytogenetic alteration in some hematological diseases such as B acute lymphoblastic leukemia or multiple myeloma, with prognostic value. However, the presence of chromosomal gains other tan trisomy 12 (+12) in chronic lymphocytic leukemia (CLL) has scarcely been reported before.
Aims
The aim of this study was to analyze, by FISH, the frequency and prognostic implications of chromosomal gains in CLL.
Methods
A retrospective review of 1,359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution, between 2004 and 2012, was carried out. Chromosomal gains were considered when a gain of at least 3 out of the 5 FISH probes used (11q22/ATM, 12q13, 13q34, 14q34/IGH, and 17p13/TP53) was observed. In addition, Next Generation Sequencing analysis was carried out to investigate the mutational status of TP53 (exons 4–11) gene.
Results
8 cases with chromosomal gains were identified out of the 1,359 CLL patients (0.59%), referred for FISH studies. One case was excluded from the analysis due to inadequate follow-up. Five cases (cases nº 3-7) presented chromosomal gains at diagnosis; the other two (case nº 1 and 2) during disease evolution and after having received treatment with chlorambucil. Four patients (57%) were female, and the median age at diagnosis was 74 years (range 63-86). The median white blood cell count at the time of diagnosis was 16 x 109/L (range, 7-67). No significant anemia or thrombocytopenia were detected in any case at diagnosis. It is noteworthy that the immunophenotype of three out of the seven cases suggested the diagnosis of atypical CLL. Serum LDH and β2microglobulin levels at diagnosis were high in 57% (4/7) and 29% of the cases (2/7), respectively. Three out of seven (43%) patients presented with splenomegaly and hepatomegaly, and 29% with more than three enlarged lymph node regions. The presence of B symptoms was detected in 29% of the cases. Of note, at the time of diagnosis most cases were classified as early stages according to Binet classification (stage A 57%; stage B 29%; stage C 14%). IGHV mutation status was available in 57% of the cases being all of them classified as unmutated pattern. Besides chromosomal gains, additional chromosomal abnormalities were detected in 57% of the patients including: 17p- (2 cases), 11q- and IGH alteration (1 case), and 13q- and IGH deletion (1case). Detailed FISH results are shown in Table I. Only one patient (case nº 7) showed a missense TP53 mutation (c.613T>G; p.Y205D) with a mutational burden of 95%. This variation was previously described as a mutation in the COSMIC database (COSM43844). This TP53 mutated case did not show 17p deletion. Six patients (86%) required treatment during follow-up with a median TTFT of 1.4 months (CI95%, 0.8-1.9). Most treated patients (4/6, 66%) required two or more chemotherapy therapies (median 3, range: 1-4), due to refractoriness or relapse. Median duration of response to first line treatment was 7 months (0-36). With a median follow-up of 66 months (6-115), 5 patients have died due to: disease progression (3 cases), infection (1 case), and cardiovascular disease (1 case). Median OS from the time of diagnosis was 66 months (CI95%, 0-174), and from the time of chromosomal gains acquisition was 20 months (CI95%, 16-24).
Conclusion
Chromosomal gains are a rare event in CLL. Our results also suggest that the presence of chromosomal gains involves poor prognosis in these patients. This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI15/01471
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Chronic lymphocytic leukemia, FISH, Prognosis
Abstract: E1046
Type: Eposter Presentation
Background
Hyperdiploidy is a common cytogenetic alteration in some hematological diseases such as B acute lymphoblastic leukemia or multiple myeloma, with prognostic value. However, the presence of chromosomal gains other tan trisomy 12 (+12) in chronic lymphocytic leukemia (CLL) has scarcely been reported before.
Aims
The aim of this study was to analyze, by FISH, the frequency and prognostic implications of chromosomal gains in CLL.
Methods
A retrospective review of 1,359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution, between 2004 and 2012, was carried out. Chromosomal gains were considered when a gain of at least 3 out of the 5 FISH probes used (11q22/ATM, 12q13, 13q34, 14q34/IGH, and 17p13/TP53) was observed. In addition, Next Generation Sequencing analysis was carried out to investigate the mutational status of TP53 (exons 4–11) gene.
Results
8 cases with chromosomal gains were identified out of the 1,359 CLL patients (0.59%), referred for FISH studies. One case was excluded from the analysis due to inadequate follow-up. Five cases (cases nº 3-7) presented chromosomal gains at diagnosis; the other two (case nº 1 and 2) during disease evolution and after having received treatment with chlorambucil. Four patients (57%) were female, and the median age at diagnosis was 74 years (range 63-86). The median white blood cell count at the time of diagnosis was 16 x 109/L (range, 7-67). No significant anemia or thrombocytopenia were detected in any case at diagnosis. It is noteworthy that the immunophenotype of three out of the seven cases suggested the diagnosis of atypical CLL. Serum LDH and β2microglobulin levels at diagnosis were high in 57% (4/7) and 29% of the cases (2/7), respectively. Three out of seven (43%) patients presented with splenomegaly and hepatomegaly, and 29% with more than three enlarged lymph node regions. The presence of B symptoms was detected in 29% of the cases. Of note, at the time of diagnosis most cases were classified as early stages according to Binet classification (stage A 57%; stage B 29%; stage C 14%). IGHV mutation status was available in 57% of the cases being all of them classified as unmutated pattern. Besides chromosomal gains, additional chromosomal abnormalities were detected in 57% of the patients including: 17p- (2 cases), 11q- and IGH alteration (1 case), and 13q- and IGH deletion (1case). Detailed FISH results are shown in Table I. Only one patient (case nº 7) showed a missense TP53 mutation (c.613T>G; p.Y205D) with a mutational burden of 95%. This variation was previously described as a mutation in the COSMIC database (COSM43844). This TP53 mutated case did not show 17p deletion. Six patients (86%) required treatment during follow-up with a median TTFT of 1.4 months (CI95%, 0.8-1.9). Most treated patients (4/6, 66%) required two or more chemotherapy therapies (median 3, range: 1-4), due to refractoriness or relapse. Median duration of response to first line treatment was 7 months (0-36). With a median follow-up of 66 months (6-115), 5 patients have died due to: disease progression (3 cases), infection (1 case), and cardiovascular disease (1 case). Median OS from the time of diagnosis was 66 months (CI95%, 0-174), and from the time of chromosomal gains acquisition was 20 months (CI95%, 16-24).
Conclusion
Chromosomal gains are a rare event in CLL. Our results also suggest that the presence of chromosomal gains involves poor prognosis in these patients. This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI15/01471
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Chronic lymphocytic leukemia, FISH, Prognosis
Type: Eposter Presentation
Background
Hyperdiploidy is a common cytogenetic alteration in some hematological diseases such as B acute lymphoblastic leukemia or multiple myeloma, with prognostic value. However, the presence of chromosomal gains other tan trisomy 12 (+12) in chronic lymphocytic leukemia (CLL) has scarcely been reported before.
Aims
The aim of this study was to analyze, by FISH, the frequency and prognostic implications of chromosomal gains in CLL.
Methods
A retrospective review of 1,359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution, between 2004 and 2012, was carried out. Chromosomal gains were considered when a gain of at least 3 out of the 5 FISH probes used (11q22/ATM, 12q13, 13q34, 14q34/IGH, and 17p13/TP53) was observed. In addition, Next Generation Sequencing analysis was carried out to investigate the mutational status of TP53 (exons 4–11) gene.
Results
8 cases with chromosomal gains were identified out of the 1,359 CLL patients (0.59%), referred for FISH studies. One case was excluded from the analysis due to inadequate follow-up. Five cases (cases nº 3-7) presented chromosomal gains at diagnosis; the other two (case nº 1 and 2) during disease evolution and after having received treatment with chlorambucil. Four patients (57%) were female, and the median age at diagnosis was 74 years (range 63-86). The median white blood cell count at the time of diagnosis was 16 x 109/L (range, 7-67). No significant anemia or thrombocytopenia were detected in any case at diagnosis. It is noteworthy that the immunophenotype of three out of the seven cases suggested the diagnosis of atypical CLL. Serum LDH and β2microglobulin levels at diagnosis were high in 57% (4/7) and 29% of the cases (2/7), respectively. Three out of seven (43%) patients presented with splenomegaly and hepatomegaly, and 29% with more than three enlarged lymph node regions. The presence of B symptoms was detected in 29% of the cases. Of note, at the time of diagnosis most cases were classified as early stages according to Binet classification (stage A 57%; stage B 29%; stage C 14%). IGHV mutation status was available in 57% of the cases being all of them classified as unmutated pattern. Besides chromosomal gains, additional chromosomal abnormalities were detected in 57% of the patients including: 17p- (2 cases), 11q- and IGH alteration (1 case), and 13q- and IGH deletion (1case). Detailed FISH results are shown in Table I. Only one patient (case nº 7) showed a missense TP53 mutation (c.613T>G; p.Y205D) with a mutational burden of 95%. This variation was previously described as a mutation in the COSMIC database (COSM43844). This TP53 mutated case did not show 17p deletion. Six patients (86%) required treatment during follow-up with a median TTFT of 1.4 months (CI95%, 0.8-1.9). Most treated patients (4/6, 66%) required two or more chemotherapy therapies (median 3, range: 1-4), due to refractoriness or relapse. Median duration of response to first line treatment was 7 months (0-36). With a median follow-up of 66 months (6-115), 5 patients have died due to: disease progression (3 cases), infection (1 case), and cardiovascular disease (1 case). Median OS from the time of diagnosis was 66 months (CI95%, 0-174), and from the time of chromosomal gains acquisition was 20 months (CI95%, 16-24).
Conclusion
Chromosomal gains are a rare event in CLL. Our results also suggest that the presence of chromosomal gains involves poor prognosis in these patients. This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI15/01471
Session topic: E-poster
Keyword(s): Chromosomal abnormality, Chronic lymphocytic leukemia, FISH, Prognosis
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