An Approach to Diagnosis of Richter Transformation in Chronic Lymphocytic Leukemia

Richter transformation (RT) is the development of high-grade lymphoma in patients with B-cell chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). CLL/SLL is a heterogenous disease with a highly variable clinical course. Disease progression in patients with CLL continues to occur even in the era of novel therapies. A small percentage of CLL patients will develop aggressive histologic transformation to diffuse large B-cell lymphoma (DLBCL), commonly known as RT. It is known that certain genetic aberrations predispose patients to RT, including mutations in NOTCH1, TP53, CDKN2A, and unmutated IGHV somatic mutations. Historically, challenges existed in making a definitive diagnosis of RT. More recently, clonal relationships between the underlying CLL and DLBCL-RT are primarily diagnosed by sequencing immunoglobulin genes. Yet, RT continues to present challenges to health-care providers in managing patients with CLL/SLL, even with novel agents. This article aims to increase advanced practitioner awareness of predictive factors for RT, clinical manifestations, and diagnostic criteria to promote early recognition and intervention. Advanced practitioners need to be cognizant of clinical signs of RT and of diagnostic criteria for an appropriate and rapid diagnosis. In doing so, the advanced practitioner can promote early diagnosis and intervention, which may improve patient outcomes, given the dismal prognosis of RT.