title: Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome.
abstract: Predictors of chronic lymphocytic leukaemia (CLL) transformation to Richter syndrome (RS) are not established and were investigated in 185 consecutive CLL cases. Actuarial incidence of RS (n = 17; all diffuse large B-cell lymphomas) at 10 years was 16.2% (95% confidence interval: 8.0-24.4%). At CLL diagnosis, prognosticators of RS by univariate analysis were IGHV homology >/=98% (P = 0.006), IGHV4-39 usage (P < 0.001), del13q14 absence (P = 0.004), expression of CD38 (P < 0.001) and ZAP70 (P = 0.004), size (P < 0.001) and number (P < 0.001) of lymph nodes, advanced Binet stage (P = 0.002), and lactate dehydrogenase (P < 0.001). Multivariate analysis, performed separately for biological and clinical variables, identified CD38 expression [Hazard ratio (HR) = 4.26; P = 0.018], IGHV4-39 usage (HR = 4.29; P = 0.018), and lymph node size >/=3 cm (HR = 9.07; P < 0.001) as independent RS prognosticators. A multivariate model simultaneously analysing biological and clinical variables identified lymph node size >/=3 cm (HR = 6.51; P = 0.001) and del13q14 absence (HR = 4.08; P = 0.031) as independent RS prognosticators. Risk factors of CLL transformation differed from risk factors of CLL progression. These results suggest that CD38 and del13q14 may identify biological subsets of CLL with different RS predisposition. Predominant nodal disease, CD38 expression, IGHV4-39 usage, and absence of del13q14 may help in predicting RS at CLL diagnosis. Close monitoring and a careful biopsy policy are needed in patients carrying transformation risk factors.
authors.affiliation: Division of Haematology, Department of Clinical and Experimental Medicine and BRMA, Amedeo Avogadro University of Eastern Piedmont and Ospedale Maggiore della Carità, Novara, Italy. rossidav@med.unipmn.it
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Michaela
authors.initials: M
authors.lastname: Cerri
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Clara
authors.initials: C
authors.lastname: Deambrogi
authors.forename: Francesca Maria
authors.initials: FM
authors.lastname: Rossi
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Lorenzo
authors.initials: L
authors.lastname: De Paoli
authors.forename: Stefania
authors.initials: S
authors.lastname: Cresta
authors.forename: Silvia
authors.initials: S
authors.lastname: Rasi
authors.forename: Valeria
authors.initials: V
authors.lastname: Spina
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschetti
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.forename: Chiara
authors.initials: C
authors.lastname: Vendramin
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bomben
authors.forename: Antonio
authors.initials: A
authors.lastname: Ramponi
authors.forename: Guido
authors.initials: G
authors.lastname: Monga
authors.forename: Annarita
authors.initials: A
authors.lastname: Conconi
authors.forename: Corrado
authors.initials: C
authors.lastname: Magnani
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D013577:Syndrome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1