title: Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated with Chemotherapy with or without Immunotherapy.
abstract: Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS) and response to treatment. We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53mutations,IGHVunmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our criteria no parameter was found to independently predict for inferior response to treatment.
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Martinelli
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Formigaro
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cavallari
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lista
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Francesca Maria
authors.initials: FM
authors.lastname: Quaglia
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ciccone
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bardi
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Volta
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tammiso
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Saccenti
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Sofritti
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Daghia
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dabusti
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tomasi
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Moretti
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.affiliation: Section of Hematology, Azienda Ospedaliero-Universitaria S.Anna, Ferrara, Italy.
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin