Haematologica (Jun 2020)

A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia

  • Jared A. Cohen,
  • Francesca Maria Rossi,
  • Antonella Zucchetto,
  • Riccardo Bomben,
  • Lodovico Terzi-di-Bergamo,
  • Kari G. Rabe,
  • Massimo Degan,
  • Agostino Steffan,
  • Jerry Polesel,
  • Enrico Santinelli,
  • Idanna Innocenti,
  • Giovanna Cutrona,
  • Giovanni D’Arena,
  • Gabriele Pozzato,
  • Francesco Zaja,
  • Annalisa Chiarenza,
  • Davide Rossi,
  • Francesco Di Raimondo,
  • Luca Laurenti,
  • Massimo Gentile,
  • Fortunato Morabito,
  • Antonino Neri,
  • Manlio Ferrarini,
  • Christopher D. Fegan,
  • Christopher J. Pepper,
  • Giovanni Del Poeta,
  • Sameer A. Parikh,
  • Neil E. Kay,
  • Valter Gattei

DOI
https://doi.org/10.3324/haematol.2019.228171
Journal volume & issue
Vol. 105, no. 6

Abstract

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We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia (CLL) developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count >32.0x103/microliter, 1 point. Low-, intermediate- and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144 / 395 / 540 / 322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage CLL, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 CLL being performed at the time of diagnosis to aid prognosis and treatment, particularly in today’s chemofree era.