International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia

Condoluci, Adalgisa; Terzi di Bergamo, Lodovico; Langerbeins, Petra; Hoechstetter, Manuela A.; Herling, Carmen D.; De Paoli, Lorenzo; Delgado, Julio; Rabe, Kari G.; Gentile, Massimo; Doubek, Michael; Mauro, Francesca R.; Chiodin, Giorgia; Mattsson, Mattias; Bahlo, Jasmin; Cutrona, Giovanna; Kotaskova, Jana; Deambrogi, Clara; Smedby, Karin E.; Spina, Valeria; Bruscaggin, Alessio; Wu, Wei; Moia, Riccardo; Bianchi, Elena; Gerber, Bernhard; Zucca, Emanuele; Gillessen, Silke; Ghielmini, Michele; Cavalli, Franco; Stussi, Georg; Hess, Mark A.; Baumann, Tycho S.; Neri, Antonino; Ferrarini, Manlio; Rosenquist, Richard; Forconi, Francesco; Foà, Robin; Pospisilova, Sarka; Morabito, Fortunato; Stilgenbauer, Stephan; Döhner, Hartmut; Parikh, Sameer A.; Wierda, William G.; Montserrat, Emili; Gaidano, Gianluca; Hallek, Michael; Rossi, Davide

doi:10.1182/blood.2019003453

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Journal article

International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia

Condoluci, Adalgisa Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Terzi di Bergamo, Lodovico Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Langerbeins, Petra Center of Integrated Oncology Cologne Bonn and German CLL Study Group, University of Cologne, Germany
Hoechstetter, Manuela A. Hospital Munich-Schwabing, German CLL Study Group, Munich, Germany
Herling, Carmen D. Center of Integrated Oncology Cologne Bonn and German CLL Study Group, University of Cologne, Germany
De Paoli, Lorenzo Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
Delgado, Julio Hospital Clinic, Barcelona, Spain
Rabe, Kari G. Mayo Clinic, Rochester, MN, USA
Gentile, Massimo Azienda Ospedaliera of Cosenza, Italy
Doubek, Michael Interní Hematologická a Onkologická Klinika (IHOK), University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic - Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Mauro, Francesca R. Division of Hematology, Sapienza University, Rome, Italy
Chiodin, Giorgia Cancer Sciences Division, University of Southampton, United Kingdom
Mattsson, Mattias Uppsala University Hospital, Sweden
Bahlo, Jasmin Center of Integrated Oncology Cologne Bonn and German CLL Study Group, University of Cologne, Germany
Cutrona, Giovanna IRCCS Ospedale Policlinico San Martino, Genoa, Italy
Kotaskova, Jana Interní Hematologická a Onkologická Klinika (IHOK), University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic - Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Deambrogi, Clara Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
Smedby, Karin E. Karolinska Institute, Stockholm, Sweden
Spina, Valeria Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Bruscaggin, Alessio Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Wu, Wei Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
Moia, Riccardo Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
Bianchi, Elena Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Gerber, Bernhard Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Zucca, Emanuele Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Gillessen, Silke Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Ghielmini, Michele Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Cavalli, Franco Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Stussi, Georg Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Hess, Mark A. University of Texas MD Anderson Cancer Center, Houston, TX, USA
Baumann, Tycho S. Hospital Clinic, Barcelona, Spain
Neri, Antonino Department of Oncology and Hemato-Oncology, University of Milan, Italy
Ferrarini, Manlio Department of Experimental Medicine, University of Genoa, Italy
Rosenquist, Richard Karolinska Institute, Stockholm, Sweden
Forconi, Francesco Cancer Sciences Division, University of Southampton, United Kingdom - Southampton University Hospital Trust, United Kingdom
Foà, Robin Division of Hematology, Sapienza University, Rome, Italy
Pospisilova, Sarka Interní Hematologická a Onkologická Klinika (IHOK), University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic - Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Morabito, Fortunato Biotechnology Research Unit Aprigliano, Cosenza, Italy - Augusta Victoria Hospital, Jerusalem, Israel
Stilgenbauer, Stephan Department of Internal Medicine III, University Hospital of Ulm, Germany
Döhner, Hartmut Department of Internal Medicine III, University Hospital of Ulm, Germany
Parikh, Sameer A. Mayo Clinic, Rochester, MN, USA
Wierda, William G. University of Texas MD Anderson Cancer Center, Houston, TX, USA
Montserrat, Emili Hospital Clinic, Barcelona, Spain - Institute of Hematology and Oncology, University of Barcelona, Spain
Gaidano, Gianluca Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
Hallek, Michael Center of Integrated Oncology Cologne Bonn and German CLL Study Group, University of Cologne, Germany
Rossi, Davide Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland

21.05.2020

Published in:

Blood. - 2020, vol. 135, no. 21, p. 1859–1869

English Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early- stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 × 109/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta- analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.

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