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 combination of germline genetic characteristics, clinical features (eg, advanced Rai stage), biologic (ζ-associated protein-70(+), CD38(+), CD49d(+)) and somatic genetic (del17p13.1 or del11q23.1) characteristics of CLL B cells, and certain CLL therapies are associated with higher risk of RS.
According to correlation analysis, a high level of lactate dehydrogenase (LDH) and CD38 positivity were found to be independent predictors of transformation to RS.
Importantly, although some risk factors predict both CLL progression and transformation to RS, others (CD38 genotype, absence of del13q14, IGHV4-39 usage, stereotyped B-cell receptor) appear to specifically predict RS.
Specific risk factors for the development of Richter's transformation in a patient with CLL have yet to be identified; however, TP53 disruption, c-MYCabnormalities, unmutated immunoglobulin heavy chain (IGHV) < 2%, non-del13q cytogenetics, CD38 gene polymorphisms, stereotypy, and VH4-39 gene usage may predispose to Richter's transformation.