TY - JOUR
T1 - 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
AU - Bulian, Pietro
AU - Rossi, Davide
AU - Forconi, Francesco
AU - Del Poeta, Giovanni
AU - Bertoni, Francesco
AU - Zucca, Emanuele
AU - Montillo, Marco
AU - Pozzato, Gabriele
AU - D'Arena, Giovanni
AU - Efremov, Dimitar G.
AU - Marasca, Roberto
AU - Lauria, Francesco
AU - Gaidano, Gianluca
AU - Gattei, Valter
AU - Laurenti, Luca
N1 - Funding Information:
Authors wish to thank dott. Michela Ternani, Institute of Haematology, Catholic University of the Sacred Heart, Rome, Italy, for clinical data collection. Supported in part by: Ministero della Salute (Ricerca Finalizzata I.R. C.C.S. and “Alleanza Contro il Cancro”), Rome; Associazione Italiana contro le Leucemie, linfomi e mielomi (A.I.L.), Venezia Section, Pramaggiore Group; Ricerca Scientifica Applicata, Regione Friuli Venezia Giulia, Trieste ("Linfonet” project); Associazione Italiana per la Ricerca sul Cancro (Investigator Grant IG-8701), Milan, Italy; Helmut Horten Foundation, San Salvatore Foundation, Fondazione per la Ricerca e la Cura sui Linfomi (Lugano, Switzerland); Progetto FIRB-Programma “Futuro in Ricerca” 2008 and PRIN 2008, MIUR, Rome, Italy; AIRC, Special Program Molecular Clinical Oncology, 5 × 1000, No. 10007, Milan, Italy; Progetto Giovani Ricercatori 2008 and Ricerca Sanitaria Finalizzata, Ministero della Salute, Rome, Italy; Ricerca Sanitaria Finalizzata, Regione Piemonte, Torino, Italy. Financial disclosures: none.
PY - 2012/1/30
Y1 - 2012/1/30
N2 - 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, β2-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, β2-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 β2-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.
AB - 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, β2-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, β2-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 β2-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.
KW - Chronic lymphocytic leukaemia
KW - Nomogram
KW - Prognosis
KW - Prognostic score
UR - http://www.scopus.com/inward/record.url?scp=84856292645&partnerID=8YFLogxK
U2 - 10.1186/1479-5876-10-18
DO - 10.1186/1479-5876-10-18
M3 - Article
SN - 1479-5876
VL - 10
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 18
ER -