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IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia

IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia
IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia
Background: Prognostic index for survival estimation by clinical-demographic variables were previously proposed in chronic lymphocytic leukemia (CLL) patients. Our objective was to test in a large retrospective cohort of CLL patients the prognostic power of biological and clinical-demographic variable in a comprehensive multivariate model. A new prognostic index was proposed.

Methods: Overall survival and time to treatment in 620 untreated CLL patients were analyzed retrospectively to evaluate the multivariate independence and predictive power of mutational status of immunoglobulin heavy chain variable gene segments (IGHV), high-risk chromosomal aberration such as 17p or 11q deletions, CD38 and ZAP-70 expression, age, gender, Binet stage, ?2-microglobulin levels, absolute lymphocyte count and number of lymph node regions.

Results: IGHV mutational status and 17p deletion were the sole biological variables with independent prognostic relevance in a multivariate model for overall survival, which included easily measurable clinical parameters (Binet staging, ?2-microglobulin levels) and demographics (age and gender). Analysis of time to treatment in Binet A patients below 70 years of age showed that IGHV was the most important predictor. A novel 6-variable clinical-biological prognostic index was developed and internally validated, which assigned 3 points for Binet C stage, 2 points/each for Binet B stage and for age > 65 years, 1 point/each for male gender, high ?2-microglobulin levels, presence of an unmutated IGHV gene status or 17p deletion. Patients were classified at low-risk (score = 0-1; 21%), intermediate-risk (score 2-5; 63% of cases), high-risk (score 6-9; 16% of cases). Projected 5-year overall survival was 98%, 90% and 58% in low-, intermediate- and high-risk groups, respectively. A nomogram for individual patient survival estimation was also proposed.

Conclusions: Data indicate that IGHV mutational status and 17p deletion may be integrated with clinical-demographic variables in new prognostic tools to estimate overall survival.
chronic lymphocytic leukaemia, prognosis, prognostic score, nomogram
1479-5876
18
Bulian, Pietro
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Rossi, Davide
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Forconi, Francesco
ba40e5ec-24ea-48d5-9a69-c0ffedaf8894
Del Poeta, Giovanni
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Bertoni, Francesco
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Zucca, Emanuele
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Montillo, Marco
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Pozzato, Gabriele
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D'Arena, Giovanni
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Efremov, Dimitar G
61782004-86fe-45a4-8960-0871e7cdd6f4
Marasca, Roberto
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Lauria, Francesco
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Gaidano, Gianluca
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Gattei, Valter
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Laurenti, Luca
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Bulian, Pietro
aa3b2489-d243-4e84-bcf5-fcd698f5f4ce
Rossi, Davide
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Forconi, Francesco
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Del Poeta, Giovanni
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Bertoni, Francesco
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Zucca, Emanuele
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Montillo, Marco
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Pozzato, Gabriele
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D'Arena, Giovanni
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Efremov, Dimitar G
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Marasca, Roberto
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Lauria, Francesco
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Gaidano, Gianluca
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Gattei, Valter
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Laurenti, Luca
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Bulian, Pietro, Rossi, Davide, Forconi, Francesco, Del Poeta, Giovanni, Bertoni, Francesco, Zucca, Emanuele, Montillo, Marco, Pozzato, Gabriele, D'Arena, Giovanni, Efremov, Dimitar G, Marasca, Roberto, Lauria, Francesco, Gaidano, Gianluca, Gattei, Valter and Laurenti, Luca (2012) IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia. Journal of Translational Medicine, 10, 18. (doi:10.1186/1479-5876-10-18). (PMID:22289136)

Record type: Article

Abstract

Background: Prognostic index for survival estimation by clinical-demographic variables were previously proposed in chronic lymphocytic leukemia (CLL) patients. Our objective was to test in a large retrospective cohort of CLL patients the prognostic power of biological and clinical-demographic variable in a comprehensive multivariate model. A new prognostic index was proposed.

Methods: Overall survival and time to treatment in 620 untreated CLL patients were analyzed retrospectively to evaluate the multivariate independence and predictive power of mutational status of immunoglobulin heavy chain variable gene segments (IGHV), high-risk chromosomal aberration such as 17p or 11q deletions, CD38 and ZAP-70 expression, age, gender, Binet stage, ?2-microglobulin levels, absolute lymphocyte count and number of lymph node regions.

Results: IGHV mutational status and 17p deletion were the sole biological variables with independent prognostic relevance in a multivariate model for overall survival, which included easily measurable clinical parameters (Binet staging, ?2-microglobulin levels) and demographics (age and gender). Analysis of time to treatment in Binet A patients below 70 years of age showed that IGHV was the most important predictor. A novel 6-variable clinical-biological prognostic index was developed and internally validated, which assigned 3 points for Binet C stage, 2 points/each for Binet B stage and for age > 65 years, 1 point/each for male gender, high ?2-microglobulin levels, presence of an unmutated IGHV gene status or 17p deletion. Patients were classified at low-risk (score = 0-1; 21%), intermediate-risk (score 2-5; 63% of cases), high-risk (score 6-9; 16% of cases). Projected 5-year overall survival was 98%, 90% and 58% in low-, intermediate- and high-risk groups, respectively. A nomogram for individual patient survival estimation was also proposed.

Conclusions: Data indicate that IGHV mutational status and 17p deletion may be integrated with clinical-demographic variables in new prognostic tools to estimate overall survival.

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More information

Published date: 30 January 2012
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: chronic lymphocytic leukaemia, prognosis, prognostic score, nomogram
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358114
URI: https://eprints.soton.ac.uk/id/eprint/358114
ISSN: 1479-5876
PURE UUID: 2fbbb69c-017c-44fb-9a11-825a9e99236b

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Date deposited: 04 Oct 2013 11:17
Last modified: 18 Jul 2017 03:31

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Contributors

Author: Pietro Bulian
Author: Davide Rossi
Author: Francesco Forconi
Author: Giovanni Del Poeta
Author: Francesco Bertoni
Author: Emanuele Zucca
Author: Marco Montillo
Author: Gabriele Pozzato
Author: Giovanni D'Arena
Author: Dimitar G Efremov
Author: Roberto Marasca
Author: Francesco Lauria
Author: Gianluca Gaidano
Author: Valter Gattei
Author: Luca Laurenti

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