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International prognostic score for asymptomatic early stage chronic lymphocytic leukemia

International prognostic score for asymptomatic early stage chronic lymphocytic leukemia
International prognostic score for asymptomatic early stage chronic lymphocytic leukemia
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
0006-4971
Condoluci, A.
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Terzi Di Bergamo, L.
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Langerbeins, P.
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Cutrona, G.
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Kotaskova, J.
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Deambrogi, C.
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Bianchi, E.
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Gerber, B.
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Zucca, E.
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Ghielmini, M.
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Cavalli, F.
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Stussi, G.
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Hess, M.
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Neri, A.
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Ferrarini, M.
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Rosenquist, R.
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Foa, R.
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Pospisilova, S.
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Morabito, F.
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Dohner, H.
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Parikh, S.A.
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Wierda, W.G.
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Montserrat, E.
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Hallek, M.
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Rossi, D.
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Condoluci, A.
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Terzi Di Bergamo, L.
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Langerbeins, P.
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Hoechstetter, M.
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Herling, C.D.
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De Paoli, L.
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Delgado, J.
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Doubek, M.
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Chiodin, G.
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Mattsson, M.
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Bahlo, J.
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Cutrona, G.
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Kotaskova, J.
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Deambrogi, C.
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Spina, V.
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Wu, W.
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Moia, R.
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Bianchi, E.
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Gerber, B.
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Zucca, E.
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Ghielmini, M.
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Cavalli, F.
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Stussi, G.
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Hess, M.
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Neri, A.
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Ferrarini, M.
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Rosenquist, R.
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Forconi, F.
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Foa, R.
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Pospisilova, S.
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Morabito, F.
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Stilgenbauer, S.
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Dohner, H.
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Parikh, S.A.
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Wierda, W.G.
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Montserrat, E.
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Gaidano, G.
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Hallek, M.
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Rossi, D.
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Condoluci, A., Terzi Di Bergamo, L., Langerbeins, P., Hoechstetter, M., Herling, C.D., De Paoli, L., Delgado, J., Rabe, K.G., Gentile, M., Doubek, M., Mauro, F., Chiodin, G., Mattsson, M., Bahlo, J., Cutrona, G., Kotaskova, J., Deambrogi, C., Smedby, K.E., Spina, V., Bruscaggin, A., Wu, W., Moia, R., Bianchi, E., Gerber, B., Zucca, E., Ghielmini, M., Cavalli, F., Stussi, G., Hess, M., Neri, A., Ferrarini, M., Rosenquist, R., Forconi, F., Foa, R., Pospisilova, S., Morabito, F., Stilgenbauer, S., Dohner, H., Parikh, S.A., Wierda, W.G., Montserrat, E., Gaidano, G., Hallek, M. and Rossi, D. (2020) International prognostic score for asymptomatic early stage chronic lymphocytic leukemia. Blood, 135 (21). (doi:10.1182/blood.2019003453).

Record type: Article

Abstract

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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International Prognostic Score for Asymptomatic Early stage Chronic Lymphocytic Leukemia - Accepted Manuscript
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Accepted/In Press date: 12 February 2020
Published date: 1 May 2020

Identifiers

Local EPrints ID: 438353
URI: http://eprints.soton.ac.uk/id/eprint/438353
ISSN: 0006-4971
PURE UUID: f788f9dc-8104-4ab8-92d2-74230cc37cbc

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Date deposited: 06 Mar 2020 17:33
Last modified: 01 May 2021 04:01

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Contributors

Author: A. Condoluci
Author: L. Terzi Di Bergamo
Author: P. Langerbeins
Author: M. Hoechstetter
Author: C.D. Herling
Author: L. De Paoli
Author: J. Delgado
Author: K.G. Rabe
Author: M. Gentile
Author: M. Doubek
Author: F. Mauro
Author: G. Chiodin
Author: M. Mattsson
Author: J. Bahlo
Author: G. Cutrona
Author: J. Kotaskova
Author: C. Deambrogi
Author: K.E. Smedby
Author: V. Spina
Author: A. Bruscaggin
Author: W. Wu
Author: R. Moia
Author: E. Bianchi
Author: B. Gerber
Author: E. Zucca
Author: M. Ghielmini
Author: F. Cavalli
Author: G. Stussi
Author: M. Hess
Author: A. Neri
Author: M. Ferrarini
Author: R. Rosenquist
Author: F. Forconi
Author: R. Foa
Author: S. Pospisilova
Author: F. Morabito
Author: S. Stilgenbauer
Author: H. Dohner
Author: S.A. Parikh
Author: W.G. Wierda
Author: E. Montserrat
Author: G. Gaidano
Author: M. Hallek
Author: D. Rossi

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