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

Jared Cohen(Centro di Riferimento Oncologico), Francesca Maria Rossi(Centro di Riferimento Oncologico), Antonella Zucchetto(Centro di Riferimento Oncologico), Riccardo Bomben(Centro di Riferimento Oncologico), Lodovico Terzi-di-Bergamo(Institute of Oncology Research), Kari G. Rabe(Mayo Clinic in Florida), Massimo Degan(Centro di Riferimento Oncologico), Agostino Steffan(Centro di Riferimento Oncologico), Jerry Polesel(Centro di Riferimento Oncologico), Enrico Santinelli(St. Eugenio Hospital), Idanna Innocenti(Università Cattolica del Sacro Cuore), Giovanna Cutrona(Ospedale Policlinico San Martino), Giovanni D’Arena(Centro di Riferimento Oncologico della Basilicata), Gabriele Pozzato(University of Trieste), Francesco Zaja(University of Trieste), Annalisa Chiarenza(Ferrarotto Hospital), Davide Rossi(Institute of Oncology Research), Francesco Di Raimondo(Ferrarotto Hospital), Luca Laurenti(Università Cattolica del Sacro Cuore), Massimo Gentile(Azienda Ospedaliera di Cosenza), Fortunato Morabito(Augusta Victoria Hospital), Antonino Neri(University of Milan), Manlio Ferrarini(University of Genoa), Chris Fegan(Cardiff University), Chris Pepper(Cardiff University), Giovanni Del Poeta(St. Eugenio Hospital), Sameer A. Parikh(Mayo Clinic in Arizona), Neil E. Kay(Mayo Clinic in Arizona), Valter Gattei(Centro di Riferimento Oncologico)
Haematologica
October 3, 2019
Cited by 22Open Access
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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 (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.


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