Five to 10 per cent of patients with CLL will develop a more aggressive form of lymphoma (diffuse large B-cell lymphoma or Hodgkin lymphoma) at some point during their disease course (termed Richter’s transformation). The managing team need to consider this possibility at every instance of disease recurrence, and weigh up the potential need for a tissue biopsy to investigate.

For more information see the optimal care pathway for people with people with Hodgkin and diffuse large B-cell lymphomas 

Features that can suggest the presence of Richter’s transformation and prompt repeat tissue biopsy of the most suspicious site include (Petrackova et al. 2021):

• new-onset B symptoms (fevers, sweats, weight loss)
• rapidly growing, or a specific site of dominant or bulky, lymphadenopathy
• markedly elevated serum LDH level or new onset of hypercalcemia
• atypical extranodal site of disease involvement such as central nervous system, kidney, lytic bone lesions etc. or significantly elevated avidity (SUVmax above 5 – 10) on FDG-PET scanning (Wang et al. 2020).

Signs and symptoms of recurrent or progressive CLL such as lymphadenopathy, increasing fatigue, fevers, sweats or unintentional weight loss and recurrent infections are usually recognised by the patient and reported at routine reviews. Lymphocytosis or developing cytopenias may be identified by regular full blood counts. Routine surveillance imaging is not recommended and rarely identifies an otherwise unrecognised manifestation of disease recurrence, and provides no long-term survival benefit for the patient.

The signs of active disease are:

• new or worsening anaemia and/or thrombocytopenia
• massive or worsening splenomegaly or lymphadenopathy
• lymphocyte doubling in less than six months, or lymphocytosis increasing by 50 per cent or more over two months
• autoimmune complications that don’t respond well to corticosteroids
• extranodal involvement impacting organ function or causing symptoms (e.g. skin, kidney, lung, spine)
• night sweats, fatigue, unintentional weight loss,