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

Abstract

Summary 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.

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

“…30 Excluding those cases in which failure was a consequence of lack of tissue, assessable results were obtained in 86.8 to 92.8% of the cases with each single probe (Table 1) A second methodological consideration should be raised concerning patient selection for this study. As in previous studies, 23 patients with progressive disease and clinically relevant adenopathy were included in our analysis. Therefore, the patient population was not representative of the entire CLL population seen at the referring centers during the study period, and FISH analysis was performed in biopsies taken in different phases of the history of the disease.…”

“…All the patients had a clonal B-cell population with CD5 þ , CD19 þ , CD23 þ and surface kappa/lambda light chain restriction. Lymph node biopsy in these patients was performed in the presence of progressive disease 23 requiring treatment, with adenopathies X3 cm. In all, 49% of these patients were untreated, 51% had received 1-3 lines of treatment (median 2 lines).…”

Telomere length is an independent predictor of survival, treatment requirement and Richter's syndrome transformation in chronic lymphocytic leukemia

“…15 Accordingly, 17/210 CLL patients had transformed to RS, accounting for a 5-year cumulative risk of transformation of …”

“…In addition, scant information is available on independent predictors of some critical events in CLL, such as clinicopathological transformation to aggressive lymphoma, also known as Richter's syndrome (RS). 15 Thus, further improvement of our current predictive tools would be advisable.…”

“…Also, we have tested TL as a risk factor of RS, an extremely severe event that most of the currently available biomarkers fail to predict. 15,30 Patients and methods…”