Treatment of Richter’s Syndrome

Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter’s syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50–60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a 18FDG PET/CT and a biopsy are recommended to confirm RS. A 18FDG PET/CT showing low uptake is helpful to rule out RS and avoid unnecessary risks and costs of performing a biopsy. A 18FDG PET/CT showing a high uptake is not diagnostic of RS but may help in the choice of the site where the biopsy is to be performed. In the setting of the diffuse large B-cell lymphoma (DLBCL) variant of RS, the definition of a clonal relationship between RS and the underlying CLL may guide the choice of treatment. If a clonal relationship is confirmed (the most common situation), rituximab-CHOP-like treatment does not guarantee long-lasting remissions, and should be used as induction therapy followed by consolidation with a stem cell transplant in physically fit patients. If the CLL and RS are clonally unrelated (the less common situation), the management should be that of a de novo DLBCL. In the setting of the rare Hodgkin lymphoma variant of RS, which is usually clonally unrelated to the CLL, ABVD with or without radiotherapy may be curative of the aggressive lymphoma.