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
Affiliations
Jared A. Cohen
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
Francesca Maria Rossi
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
Antonella Zucchetto
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
Riccardo Bomben
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
Lodovico Terzi-di-Bergamo
Institute of Oncology Research, Bellinzona, Switzerland
Kari G. Rabe
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Massimo Degan
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
Agostino Steffan
Immunopathology and Cancer Biomarkers, Centro di RiferimentoOncologico, I.R.C.C.S., Aviano (PN), Italy
Jerry Polesel
Unit of Cancer Epidemiology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
Enrico Santinelli
Division of Haematology, S. Eugenio Hospital and University of Tor Vergata, Rome, Italy
Idanna Innocenti
Hematology Institute, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy
Giovanna Cutrona
UO Molecular Pathology, Ospedale Policlinico San Martino IRCCS, Genova, Italy
Giovanni D’Arena
Onco-Haematology Department, Centro di Riferimento Oncologico della Basilicata, I.R.C.C.S., Rionero in Vulture, Italy
Gabriele Pozzato
Department of Internal Medicine and Haematology, Maggiore General Hospital, University of Trieste, Trieste, Italy
Francesco Zaja
Department of Internal Medicine and Haematology, Maggiore General Hospital, University of Trieste, Trieste, Italy
Annalisa Chiarenza
Division of Haematology, Ferrarotto Hospital, Catania, Italy
Davide Rossi
Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland;Universita’ della Svizzera Italiana, Lugano, Switzerland
Francesco Di Raimondo
Division of Haematology, Ferrarotto Hospital, Catania, Italy
Luca Laurenti
Hematology Institute, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy
Massimo Gentile
Hematology Unit, AO, Cosenza, Italy;Biotechnology Research Unit, Aprigliano, Cosenza, Italy
Fortunato Morabito
Biotechnology Research Unit, Aprigliano, Cosenza, Italy;Hematogy Department and Bone Marrow Transplant Unit, Cancer Care Center, Augusta Victoria Hospital, East Jerusalem, Israel
Antonino Neri
Hematology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy
Manlio Ferrarini
Department of Experimental Medicine, University of Genova, Genova, Italy
Christopher D. Fegan
Division of Cancer and Genetics, Cardiff University, School of Medicine, Heath Park, Cardiff, UK
Christopher J. Pepper
Division of Cancer and Genetics, Cardiff University, School of Medicine, Heath Park, Cardiff, UK;University of Sussex, Brighton and Sussex Medical School, Brighton, UK
Giovanni Del Poeta
Division of Haematology, S. Eugenio Hospital and University of Tor Vergata, Rome, Italy
Sameer A. Parikh
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
Neil E. Kay
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
Valter Gattei
Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
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.
