Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome.
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.
Rossi
Davide
D
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
Cerri
Michaela
M
Capello
Daniela
D
Deambrogi
Clara
C
Rossi
Francesca Maria
FM
Zucchetto
Antonella
A
De Paoli
Lorenzo
L
Cresta
Stefania
S
Rasi
Silvia
S
Spina
Valeria
V
Franceschetti
Silvia
S
Lunghi
Monia
M
Vendramin
Chiara
C
Bomben
Riccardo
R
Ramponi
Antonio
A
Monga
Guido
G
Conconi
Annarita
A
Magnani
Corrado
C
Gattei
Valter
V
Gaidano
Gianluca
G
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
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1