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AMONG CLL PATIENTS WITH MULTIPLE FISH ABNORMALITIES, 13Q AND 11Q DELETIONS ENTAIL THE COMMONEST COMBINATION IN CONTRAST TO 11Q AND 17P DELETIONS, BEING THE COMBINATION WITH WORSE OUTCOME
Author(s): ,
Isabel González-Gascón Y Marín
Affiliations:
Hematology,Hospital Universitario Infanta Leonor,MADRID,Spain;Medicine,Universidad Complutense de Madrid,MADRID,Spain
,
José Angel Hernández
Affiliations:
Hematology,Hospital Universitario Infanta Leonor,MADRID,Spain;Medicine,Universidad Complutense de Madrid,MADRID,Spain
,
María Hernánez-Sanchez
Affiliations:
Centro de Investigación del Cáncer-IBMCC, Universidad de Salamanca, Spain (USAL-CSIC),Salamanca,Spain
,
Ana Eugenia Rodriguez-Vicente
Affiliations:
Centro de Investigación del Cáncer-IBMCC, Universidad de Salamanca, Spain (USAL-CSIC),Salamanca,Spain
,
Anna Puiggros
Affiliations:
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar,Barcelona,Spain;Grup de Recerca Translacional en Neoplàsies Hematològiques, Programa de Recerca en Càncer, Institut Hospital del Mar d
,
Rosa Collado
Affiliations:
Hematology,Consorcio Hospital General Universitario,Valencia,Spain
,
Elisa Luño
Affiliations:
Hematology,Hospital Universitario Central de Asturias,Oviedo,Spain
,
Teresa González
Affiliations:
Fundación Pública Galega de Medicina Xenómica,Santiago de Compostela,Spain
,
Neus Ruiz-Xivillé
Affiliations:
Laboratori Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona,Barcelona,Spain
,
Margarita Ortega
Affiliations:
Laboratorio de Citogenética y Servicio de Hematología,Hospital Vall d'Hebron,Barcelona,Spain
,
Eva Gimeno
Affiliations:
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar,Barcelona,Spain
,
Carolina Muñoz
Affiliations:
Hematology,Hospital Universitario Infanta Leonor,Madrid,Spain
,
Maria Stephania Infante
Affiliations:
Hematology,Hospital Universitario Infanta Leonor,Madrid,Spain
,
Julio Delgado
Affiliations:
Hematology,Hospital Clinic and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS),Barcelona,Spain
,
Ana Aventín
Affiliations:
Hematología,Hospital Sant Pau,Barcelona,Spain
,
Maria Teresa Vargas
Affiliations:
Hospital Universitario Virgen de la Macarena,Sevilla,Spain
,
Marcos González
Affiliations:
Hematologia,IBSAL-Hospital Universitario de Salamanca,Salamanca,Spain
,
Francesc Bosch
Affiliations:
Hematology,Hospital Vall d'Hebron,Barcelona,Spain
,
Blanca Espinet
Affiliations:
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar,Barcelona,Spain
Jesús María Hernández-Rivas
Affiliations:
Hematologia,IBSAL-Hospital Universitario de Salamanca,Salamanca,Spain;Centro de Investigación del Cáncer-IBMCC, Universidad de Salamanca, Spain (USAL-CSIC),Salamanca,Spain
(Abstract release date: 05/19/16) EHA Library. González-Gascón y Marín I. 06/09/16; 132592; E1043
Dr. Isabel González-Gascón y Marín
Dr. Isabel González-Gascón y Marín
Contributions
Abstract
Abstract: E1043

Type: Eposter Presentation

Background
Fluorescence in-situ hybridization (FISH) defines a hierarchy of genetic changes that predicts survival in CLL. However, multiple abnormalities (MA) may also occur and little is known about its distribution and clinical impact.

Aims
To assess the frequency and clinical outcome of 245 patients with CLL and  MA detected by FISH in a database containing clinical and biological data.

Methods
Cases with more than one FISH abnormality were retrieved from the database. FISH abnormalities included in the routine CLL FISH panel (13q-, 11q-, 17p- and +12) were taken into account.

Results
MA were detected in 245 out of 1743 CLL cases (14%). FISH studies were performed at diagnosis (FISH-d) in 154 cases (61%), and during disease evolution (FISH-e) in 91 cases (38%). Among the 91 cases from the group of FISH-e, 26 cases (11%) had a prior FISH without MA, and 39 cases (16%) had received treatment for CLL before FISH. The most frequent associations in the group of FISH-d were the combinations of 13q- with 11q- observed in 52 cases (33.8%), followed by 13q- with 17p- (37 cases, 24%), and 13q- with +12 (28 cases, 18.8%). By contrast, in the group of FISH-e 13q- and 17p- were the most prevalent partners (28 cases, 31%) followed by 13q- and 11q- (25 cases, 27%) and +12 and 17p- (12 cases, 13%). More than 2 abnormalities were observed in a low proportion of cases: 17 (11%) in the group of FISH-d, and 7 (7.6%) in the group of FISH-e. Interestingly, most of them included 17p- (14/17 FISH-d; 6/7 FISH-e). The weirdest combination was 11q- and 17p-, only observed in 5 cases (3.2%) in the group FISH-d and 2 cases (2.1%) in the group FISH-e. Globally, 17p- was found in more cases during disease evolution (48 cases, 52%) than at the moment of diagnosis (66 cases, 42%). Moreover 17p- appeared as the major clone in a very low proportion of cases in both groups, whereas 13q- or +12 where observed more frequently as the major clone, suggesting 13q- or +12 as early events, in contrast with 17p-. Overall survival (OS) and time to first therapy (TTFT) were analyzed in the group of FISH-d, being respectively 68 months, and 25 months, for the whole series. The combination of 13q- and 11q- showed the larger OS (75 months), while CLL with 13q- and 17p- showed the shorter OS (37 months). Moreover the presence of 17p- was associated with a shorter OS (63 m vs 75 m, p=0.02). Regarding TTFT, CLL with 13q- and +12 showed a median TTFT of 53 months while the CLLs with 17p- and 11q- only had 4 months of TTFT (p=0.017) (Figure 1).

Conclusion
MA were observed in 14% of CLL cases, representing a heterogeneous group. The distribution among combinations was unequal. The combinations of 13q- with 11q- and 17p- were the most frequent associations, in contrast to 11q- and 17p-, observed in a minority of the cases. 17p- often occurred during disease evolution involving minority clones. MA entailed poor prognosis when emerged at diagnosis, probably due to the high incidence of bad prognosis aberrations such as 17p- and 11q-. On behalf of Grupo Español de Leucemia Linfática Crónica (GELLC) and Grupo Cooperativo Español de Citogenética Hematológica (GCECGH)



Session topic: E-poster

Keyword(s): Chronic lymphocytic leukemia, FISH, Prognosis
Abstract: E1043

Type: Eposter Presentation

Background
Fluorescence in-situ hybridization (FISH) defines a hierarchy of genetic changes that predicts survival in CLL. However, multiple abnormalities (MA) may also occur and little is known about its distribution and clinical impact.

Aims
To assess the frequency and clinical outcome of 245 patients with CLL and  MA detected by FISH in a database containing clinical and biological data.

Methods
Cases with more than one FISH abnormality were retrieved from the database. FISH abnormalities included in the routine CLL FISH panel (13q-, 11q-, 17p- and +12) were taken into account.

Results
MA were detected in 245 out of 1743 CLL cases (14%). FISH studies were performed at diagnosis (FISH-d) in 154 cases (61%), and during disease evolution (FISH-e) in 91 cases (38%). Among the 91 cases from the group of FISH-e, 26 cases (11%) had a prior FISH without MA, and 39 cases (16%) had received treatment for CLL before FISH. The most frequent associations in the group of FISH-d were the combinations of 13q- with 11q- observed in 52 cases (33.8%), followed by 13q- with 17p- (37 cases, 24%), and 13q- with +12 (28 cases, 18.8%). By contrast, in the group of FISH-e 13q- and 17p- were the most prevalent partners (28 cases, 31%) followed by 13q- and 11q- (25 cases, 27%) and +12 and 17p- (12 cases, 13%). More than 2 abnormalities were observed in a low proportion of cases: 17 (11%) in the group of FISH-d, and 7 (7.6%) in the group of FISH-e. Interestingly, most of them included 17p- (14/17 FISH-d; 6/7 FISH-e). The weirdest combination was 11q- and 17p-, only observed in 5 cases (3.2%) in the group FISH-d and 2 cases (2.1%) in the group FISH-e. Globally, 17p- was found in more cases during disease evolution (48 cases, 52%) than at the moment of diagnosis (66 cases, 42%). Moreover 17p- appeared as the major clone in a very low proportion of cases in both groups, whereas 13q- or +12 where observed more frequently as the major clone, suggesting 13q- or +12 as early events, in contrast with 17p-. Overall survival (OS) and time to first therapy (TTFT) were analyzed in the group of FISH-d, being respectively 68 months, and 25 months, for the whole series. The combination of 13q- and 11q- showed the larger OS (75 months), while CLL with 13q- and 17p- showed the shorter OS (37 months). Moreover the presence of 17p- was associated with a shorter OS (63 m vs 75 m, p=0.02). Regarding TTFT, CLL with 13q- and +12 showed a median TTFT of 53 months while the CLLs with 17p- and 11q- only had 4 months of TTFT (p=0.017) (Figure 1).

Conclusion
MA were observed in 14% of CLL cases, representing a heterogeneous group. The distribution among combinations was unequal. The combinations of 13q- with 11q- and 17p- were the most frequent associations, in contrast to 11q- and 17p-, observed in a minority of the cases. 17p- often occurred during disease evolution involving minority clones. MA entailed poor prognosis when emerged at diagnosis, probably due to the high incidence of bad prognosis aberrations such as 17p- and 11q-. On behalf of Grupo Español de Leucemia Linfática Crónica (GELLC) and Grupo Cooperativo Español de Citogenética Hematológica (GCECGH)



Session topic: E-poster

Keyword(s): Chronic lymphocytic leukemia, FISH, Prognosis

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