International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1859-1869
Number of pages11
JournalBlood
Volume135
Issue number21
DOIs
StatePublished - May 21 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Condoluci, A., Terzi di Bergamo, L., Langerbeins, P., Hoechstetter, M. A., Herling, C. D., De Paoli, L., Delgado, J., Rabe, K. G., Gentile, M., Doubek, M., Mauro, F. R., Chiodin, G., Mattsson, M., Bahlo, J., Cutrona, G., Kotaskova, J., Deambrogi, C., Smedby, K. E., Spina, V., ... Rossi, D. (2020). International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia. Blood, 135(21), 1859-1869. https://doi.org/10.1182/blood.2019003453