TY - JOUR
T1 - International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia
AU - Condoluci, Adalgisa
AU - Di Bergamo, Lodovico Terzi
AU - Langerbeins, Petra
AU - Hoechstetter, Manuela A.
AU - Herling, Carmen D.
AU - De Paoli, Lorenzo
AU - Delgado, Julio
AU - Rabe, Kari G.
AU - Gentile, Massimo
AU - Doubek, Michael
AU - Mauro, Francesca R.
AU - Chiodin, Giorgia
AU - Mattsson, Mattias
AU - Bahlo, Jasmin
AU - Cutrona, Giovanna
AU - Kotaskova, Jana
AU - Deambrogi, Clara
AU - Smedby, Karin E.
AU - Spina, Valeria
AU - Bruscaggin, Alessio
AU - Wu, Wei
AU - Moia, Riccardo
AU - Bianchi, Elena
AU - Gerber, Bernhard
AU - Zucca, Emanuele
AU - Gillessen, Silke
AU - Ghielmini, Michele
AU - Cavalli, Franco
AU - Stussi, Georg
AU - Hess, Mark A.
AU - Baumann, Tycho S.
AU - Neri, Antonino
AU - Ferrarini, Manlio
AU - Rosenquist, Richard
AU - Forconi, Francesco
AU - Foà, Robin
AU - Pospisilova, Sarka
AU - Morabito, Fortunato
AU - Stilgenbauer, Stephan
AU - Döhner, Hartmut
AU - Parikh, Sameer A.
AU - Wierda, William G.
AU - Montserrat, Emili
AU - Gaidano, Gianluca
AU - Hallek, Michael
AU - Rossi, Davide
N1 - Funding Information:
This study was supported by Swiss Cancer League, ID HSR-4660-11-2018, Bern, Switzerland; Research Advisory Board of the Ente Ospe-daliero Cantonale, Bellinzona, Switzerland; European Research Council Consolidator Grant CLLCLONE ID: 772051; Grant No. 320030_169670/1 Swiss National Science Foundation, Berne, Switzerland; Fondazione Fidinam, Lugano, Switzerland; Nelia & Amadeo Barletta Foundation, Lausanne, Switzerland; Fond’Action, Lausanne, Switzerland; Translational Research Program, No. 6594-20, The Leukemia & Lymphoma Society, New York; AIRC 5x1000, No. 21198, Associazione Italiana per la Ricerca sul Cancro Foundation, Milan, Italy; PRIN 2017 No. 2015ZMRFEA_004, MIUR, Rome, Italy; Italian Ministry of Health 5x1000 funds 2014 and 2016, Compagnia S. Paolo Turin Italy, project 2017.0526; Swedish Cancer Society, Swedish Research Council, Knut and Alice Wallenberg Foundation, Karolinska Insti-tutet, Karolinska University Hospital, and Radiumhemmets Forskningsfonder, Stockholm, Sweden; and MH CR grants No. NV19-03-00091 and DRO FNBr, 65269705, MEYS CR under the project CEITEC 2020 (LQ1601).
Publisher Copyright:
©2020 by The American Society of Hematology.
PY - 2020/5
Y1 - 2020/5
N2 - Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with earlystage 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 (n54933) 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 153109/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.
AB - Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with earlystage 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 (n54933) 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 153109/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.
KW - IPS-E can be helpful in patients counseling and design of clinical trials.
KW - IPS-E is a simple and robust prognostic model for earlystage CLL.
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U2 - 10.1182/BLOOD.2019003453
DO - 10.1182/BLOOD.2019003453
M3 - Article
C2 - 32267500
AN - SCOPUS:85085157110
SN - 0006-4971
VL - 135
SP - 1859
EP - 1869
JO - Blood
JF - Blood
IS - 21
ER -