Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome

Davide Rossi, Michaela Cerri, Daniela Capello, Clara Deambrogi, Francesca Maria Rossi, Antonella Zucchetto, Lorenzo De Paoli, Stefania Cresta, Silvia Rasi, Valeria Spina, Silvia Franceschetti, Monia Lunghi, Chiara Vendramin, Riccardo Bomben, Antonio Ramponi, Guido Monga, Annarita Conconi, Corrado Magnani, Valter Gattei, Gianluca Gaidano

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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.

Original languageEnglish
Pages (from-to)202-215
Number of pages14
JournalBritish Journal of Haematology
Volume142
Issue number2
DOIs
Publication statusPublished - Jul 2008

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B-Cell Chronic Lymphocytic Leukemia
Lymph Nodes
Lymphoma, Large B-Cell, Diffuse
L-Lactate Dehydrogenase
Multivariate Analysis
Confidence Intervals
Biopsy
Incidence

Keywords

  • Chronic lymphocytic leukaemia
  • Diffuse large B-cell lymphoma
  • Richter syndrome

ASJC Scopus subject areas

  • Hematology

Cite this

Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. / Rossi, Davide; Cerri, Michaela; Capello, Daniela; Deambrogi, Clara; Rossi, Francesca Maria; Zucchetto, Antonella; De Paoli, Lorenzo; Cresta, Stefania; Rasi, Silvia; Spina, Valeria; Franceschetti, Silvia; Lunghi, Monia; Vendramin, Chiara; Bomben, Riccardo; Ramponi, Antonio; Monga, Guido; Conconi, Annarita; Magnani, Corrado; Gattei, Valter; Gaidano, Gianluca.

In: British Journal of Haematology, Vol. 142, No. 2, 07.2008, p. 202-215.

Research output: Contribution to journalArticle

Rossi, D, Cerri, M, Capello, D, Deambrogi, C, Rossi, FM, Zucchetto, A, De Paoli, L, Cresta, S, Rasi, S, Spina, V, Franceschetti, S, Lunghi, M, Vendramin, C, Bomben, R, Ramponi, A, Monga, G, Conconi, A, Magnani, C, Gattei, V & Gaidano, G 2008, 'Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome', British Journal of Haematology, vol. 142, no. 2, pp. 202-215. https://doi.org/10.1111/j.1365-2141.2008.07166.x
Rossi, Davide ; Cerri, Michaela ; Capello, Daniela ; Deambrogi, Clara ; Rossi, Francesca Maria ; Zucchetto, Antonella ; De Paoli, Lorenzo ; Cresta, Stefania ; Rasi, Silvia ; Spina, Valeria ; Franceschetti, Silvia ; Lunghi, Monia ; Vendramin, Chiara ; Bomben, Riccardo ; Ramponi, Antonio ; Monga, Guido ; Conconi, Annarita ; Magnani, Corrado ; Gattei, Valter ; Gaidano, Gianluca. / Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. In: British Journal of Haematology. 2008 ; Vol. 142, No. 2. pp. 202-215.
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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.",
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AU - Rossi, Francesca Maria

AU - Zucchetto, Antonella

AU - De Paoli, Lorenzo

AU - Cresta, Stefania

AU - Rasi, Silvia

AU - Spina, Valeria

AU - Franceschetti, Silvia

AU - Lunghi, Monia

AU - Vendramin, Chiara

AU - Bomben, Riccardo

AU - Ramponi, Antonio

AU - Monga, Guido

AU - Conconi, Annarita

AU - Magnani, Corrado

AU - Gattei, Valter

AU - Gaidano, Gianluca

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N2 - 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.

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