Chapter 18: The Chronic Lymphocytic Leukaemias

The Chronic Lymphocytic Leukaemias academic overview examines the group of malignancies known as the chronic lymphocytic leukaemias, which are defined by the pathological accumulation of mature B- or T-cell lymphocytes in the blood, bone marrow, and secondary lymphoid organs. Most patients are older adults who are diagnosed incidentally through routine blood counts, although some present with enlarged lymph nodes, an enlarged spleen, or systemic symptoms. The most prevalent form is B-cell chronic lymphocytic leukaemia (CLL), which is frequently preceded by a precursor state called monoclonal B-cell lymphocytosis and is characterized by neoplastic cells that survive longer than normal lymphocytes due to impaired programmed cell death. Diagnosis is primarily achieved through flow cytometry, identifying a clonal population with specific markers such as CD5 and CD23. The text highlights the critical role of clinical staging, using the Binet and Rai systems, alongside molecular genetics to predict disease progression and guide therapy. Specifically, chromosomal abnormalities like the 17p deletion and the mutation status of the immunoglobulin heavy-chain variable region genes are essential prognostic indicators. While many patients require only observation initially, active disease is managed with a modern arsenal of targeted therapies. This includes Bruton kinase inhibitors like ibrutinib, BCL-2 inhibitors such as venetoclax, and various monoclonal antibodies, which have largely replaced or supplemented traditional cytotoxic chemotherapy. The chapter also details less common variants, such as hairy cell leukaemia—noted for its distinct "hairy" cellular projections and high response rates to specific purine analogues—and B-cell prolymphocytic leukaemia. Furthermore, it addresses T-cell disorders like large granular lymphocytic leukaemia and adult T-cell leukaemia/lymphoma, the latter of which is uniquely associated with the HTLV-1 retrovirus. Complications such as secondary autoimmunity, severe immune suppression leading to recurrent infections, and the potential for high-grade Richter transformation are also thoroughly discussed to provide a complete understanding of these chronic lymphoid conditions.