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 GentileFortunato Morabito, Antonino Neri, Manlio Ferrarini, Christopher D. Fegan, Christopher J. Pepper, Giovanni Del Poeta, Sameer A. Parikh, Neil E. Kay, Valter Gattei

Research output: Contribution to journalArticle

Abstract

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia 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 chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era.
Original languageEnglish
JournalHaematologica
DOIs
Publication statusPublished - 2019

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B-Cell Chronic Lymphocytic Leukemia
Immunoglobulin Heavy Chain Genes
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 17
Trisomy
Leukocyte Count
Italy
Regression Analysis

Keywords

  • Chronic Lymphocytic Leukemia
  • Cytogenetics and Molecular Genetics
  • Immunophenotyping

Cite this

A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia. / Cohen, Jared A.; Rossi, Francesca Maria; Zucchetto, Antonella; Bomben, Riccardo; Terzi-di-Bergamo, Lodovico; Rabe, Kari G.; Degan, Massimo; Steffan, Agostino; Polesel, Jerry; Santinelli, Enrico; Innocenti, Idanna; Cutrona, Giovanna; D' Arena, Giovanni; Pozzato, Gabriele; Zaja, Francesco; Chiarenza, Annalisa; Rossi, Davide; Di Raimondo, Francesco; Laurenti, Luca; Gentile, Massimo; Morabito, Fortunato; Neri, Antonino; Ferrarini, Manlio; Fegan, Christopher D.; Pepper, Christopher J.; Del Poeta, Giovanni; Parikh, Sameer A.; Kay, Neil E.; Gattei, Valter.

In: Haematologica, 2019.

Research output: Contribution to journalArticle

Cohen, JA, Rossi, FM, Zucchetto, A, Bomben, R, Terzi-di-Bergamo, L, Rabe, KG, Degan, M, Steffan, A, Polesel, J, Santinelli, E, Innocenti, I, Cutrona, G, D' Arena, G, Pozzato, G, Zaja, F, Chiarenza, A, Rossi, D, Di Raimondo, F, Laurenti, L, Gentile, M, Morabito, F, Neri, A, Ferrarini, M, Fegan, CD, Pepper, CJ, Del Poeta, G, Parikh, SA, Kay, NE & Gattei, V 2019, 'A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia.', Haematologica. https://doi.org/10.3324/haematol.2019.228171
Cohen, Jared A. ; Rossi, Francesca Maria ; Zucchetto, Antonella ; Bomben, Riccardo ; Terzi-di-Bergamo, Lodovico ; Rabe, Kari G. ; Degan, Massimo ; Steffan, Agostino ; Polesel, Jerry ; Santinelli, Enrico ; Innocenti, Idanna ; Cutrona, Giovanna ; D' Arena, Giovanni ; Pozzato, Gabriele ; Zaja, Francesco ; Chiarenza, Annalisa ; Rossi, Davide ; Di Raimondo, Francesco ; Laurenti, Luca ; Gentile, Massimo ; Morabito, Fortunato ; Neri, Antonino ; Ferrarini, Manlio ; Fegan, Christopher D. ; Pepper, Christopher J. ; Del Poeta, Giovanni ; Parikh, Sameer A. ; Kay, Neil E. ; Gattei, Valter. / A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia. In: Haematologica. 2019.
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abstract = "We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia 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 chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era.",
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T1 - A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia.

AU - Cohen, Jared A.

AU - Rossi, Francesca Maria

AU - Zucchetto, Antonella

AU - Bomben, Riccardo

AU - Terzi-di-Bergamo, Lodovico

AU - Rabe, Kari G.

AU - Degan, Massimo

AU - Steffan, Agostino

AU - Polesel, Jerry

AU - Santinelli, Enrico

AU - Innocenti, Idanna

AU - Cutrona, Giovanna

AU - D' Arena, Giovanni

AU - Pozzato, Gabriele

AU - Zaja, Francesco

AU - Chiarenza, Annalisa

AU - Rossi, Davide

AU - Di Raimondo, Francesco

AU - Laurenti, Luca

AU - Gentile, Massimo

AU - Morabito, Fortunato

AU - Neri, Antonino

AU - Ferrarini, Manlio

AU - Fegan, Christopher D.

AU - Pepper, Christopher J.

AU - Del Poeta, Giovanni

AU - Parikh, Sameer A.

AU - Kay, Neil E.

AU - Gattei, Valter

PY - 2019

Y1 - 2019

N2 - We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia 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 chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era.

AB - We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia 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 chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era.

KW - Chronic Lymphocytic Leukemia

KW - Cytogenetics and Molecular Genetics

KW - Immunophenotyping

U2 - 10.3324/haematol.2019.228171

DO - 10.3324/haematol.2019.228171

M3 - Article

JO - Haematologica

JF - Haematologica

SN - 0390-6078

ER -