Page 155 - Haematologica - Vol. 105 n. 6 - June 2020

Chronic Lymphocytic Leukemia
A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia
Jared A. Cohen,1 Francesca Maria Rossi,1 Antonella Zucchetto,1 Riccardo Bomben,1 Lodovico Terzi-di-Bergamo,2 Kari G. Rabe,3 Massimo Degan,1 Agostino Steffan,4 Jerry Polesel,5 Enrico Santinelli,6 Idanna Innocenti,7 Giovanna Cutrona,8 Giovanni D’Arena,9 Gabriele Pozzato,10 Francesco Zaja,10 Annalisa Chiarenza,11 Davide Rossi,12,13 Francesco Di Raimondo,11 Luca Laurenti,7 Massimo Gentile,14,15 Fortunato Morabito,15,16 Antonino Neri,17 Manlio Ferrarini,18 Christopher D. Fegan,19 Christopher J. Pepper,19,20 Giovanni Del Poeta,6 Sameer A. Parikh,21 Neil E. Kay21 and Valter Gattei1
1Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy; 2Institute of Oncology Research, Bellinzona, Switzerland; 3Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 4Immunopathology and Cancer Biomarkers, Centro di RiferimentoOncologico, I.R.C.C.S., Aviano (PN), Italy; 5Unit of Cancer Epidemiology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy; 6Division of Haematology, S. Eugenio Hospital and University of Tor Vergata, Rome, Italy; 7Hematology Institute, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy; 8UO Molecular Pathology, Ospedale Policlinico San Martino IRCCS, Genova, Italy; 9Onco-Haematology Department, Centro di Riferimento Oncologico della Basilicata, I.R.C.C.S., Rionero in Vulture, Italy; 10Department of Internal Medicine and Haematology, Maggiore General Hospital, University of Trieste, Trieste, Italy; 11Division of Haematology, Ferrarotto Hospital, Catania, Italy; 12Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; 13Universita’ della Svizzera Italiana, Lugano, Switzerland; 14Hematology Unit, AO, Cosenza, Italy; 15Biotechnology Research Unit, Aprigliano, Cosenza, Italy; 16Hematogy Department and Bone Marrow Transplant Unit, Cancer Care Center, Augusta Victoria Hospital, East Jerusalem, Israel; and 17Hematology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; 18Department of Experimental Medicine, University of Genova, Genova, Italy; 19Division of Cancer and Genetics, Cardiff University, School of Medicine, Heath Park, Cardiff, UK; 20University of Sussex, Brighton and Sussex Medical School, Brighton, UK and 21Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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 iden- tified 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 inde- pendent 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 sup- port immunocytogenetic analysis in Rai 0 CLL being performed at the time of diagnosis to aid prognosis and treatment, particularly in today’s chemo- free era.
Ferrata Storti Foundation
Haematologica 2020 Volume 105(6):1613-1620
Correspondence:
JARED A. COHEN
jcoen781@gmail.com
VALTER GATTEI
vgattei@cro.it
Received: June 3, 2019. Accepted: October 2, 2019. Pre-published: October 3, 2019.
doi:10.3324/haematol.2019.228171
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/6/1613
©2020 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2020; 105(6)
1613
ARTICLE