Richter transformation (RT) is the development of an aggressive lymphoma arising on the background of chronic lymphocytic leukaemia (CLL).1 RT is uncommon, challenging to treat, very distinct from de novo diffuse large B-cell lymphoma (DLBCL) and requires specific guidance. RT occurs in 2–10% of CLL patients, usually during the disease course rather than at presentation, representing a transformation rate of 0·5–1% per CLL patient per year.2-5 RT should be suspected when a CLL patient develops one or more new ‘B symptoms’, asymmetric, rapidly progressive lymphadenopathy, or a sudden lactate dehydrogenase (LDH) rise. RT presents as DLBCL-RT in ˜90%, but can present as Hodgkin lymphoma (HL-RT; ˜10%) or rarely as histiocytic/dendritic cell sarcoma or other forms of lymphoma (<1%).6 An important consideration is whether RT is clonally derived from or unrelated to the original CLL, as these two states have distinct clinical and pathological characteristics. Strictly speaking, RT refers to clonally related cases with Richter syndrome, but since the clonal origin is often unknown, the term RT includes all cases. Clonally related RT has an aggressive course, higher rates of treatment resistance and TP53 aberrations compared with clonally unrelated disease, where outcomes are more akin to de novo DLBCL. A clonal relationship is more common in DLBCL-RT (70–80% of cases), compared with HL-RT where it is seen in 30–40%.5 Genetic clonality studies [i.e. sequencing analysis of immunoglobulin heavy chain variable region (IgHV) genes] are not currently routinely performed in practice at most institutions (Fig 1).
Declaration of Interests
The BSH paid the expenses incurred during the writing of this guidance. None of the authors had conflicts of interest to declare. All authors have made a declaration of interests to the BSH and Task Force Chairs which may be viewed on request.