Chronic Leukaemia

Chronic leukaemias are typically more indolent than their acute counterparts. CLL is the most common leukaemia in the Western world, often diagnosed incidentally on FBC showing an absolute lymphocytosis (>5 x 10^9/L). It affects older adults (median age 70) and may not requiring treatment for years ('watch and wait'). Complications of CLL include autoimmune haemolytic anaemia (AIHA) and Richter's transformation into high-grade lymphoma. CML is a myeloproliferative neoplasm characterized by the t(9;22) Philadelphia chromosome, leading to the BCR-ABL1 fusion gene. CML presents with massively increased white cell counts (predominantly neutrophils and myelocytes) and splenomegaly. It progresses through chronic, accelerated, and blast phases. The discovery of Tyrosine Kinase Inhibitors (TKIs) like Imatinib has transformed CML from a fatal disease to a manageable chronic condition.

CLL: Clonal expansion of mature B-lymphocytes that express CD5 and CD23. These cells are functionally incompetent, leading to hypogammaglobulinaemia and increased infection risk. CML: A single haematopoietic stem cell acquires the t(9;22) translocation, where the ABL1 gene from chromosome 9 moves to the BCR gene on chromosome 22. The resulting BCR-ABL1 protein is a constitutively active tyrosine kinase that promotes uncontrolled cell proliferation and suppresses apoptosis. This affects the myeloid lineage, causing an accumulation of granulocytes at all stages of development.

CLL Presentation: Often asymptomatic. If symptomatic: lymphadenopathy (painless, rubbery), hepatosplenomegaly, and B-symptoms. Infections are common. CML Presentation: Often presents with symptoms of hypermetabolism (weight loss, sweats) or massive splenomegaly (abdominal discomfort, early satiety). Signs of anaemia or gout (due to high cell turnover) may be present. CML Blast Crisis: Progresses to a state indistinguishable from acute leukaemia (AML or ALL), which is often refractory to treatment.

CLL: Bloods: FBC (lymphocytosis >5), Blood film (Smudge/Smear cells). Flow cytometry (CD5/CD19/CD23 positive). Bone marrow: Not always needed but shows lymphocytic infiltration. CML: Bloods: FBC (Very high WBC, full spectrum of myeloid cells - 'myelocytes, metamyelocytes, bread and butter' film, high basophils/eosinophils), Low or high platelets. Cytogenetics: FISH or PCR for the BCR-ABL1 fusion gene (Philadelphia chromosome). Bone marrow: Hypercellular Myelopoiesis.

CLL: 'Watch and Wait' for asymptomatic early-stage disease. Indications for treatment: Progressive marrow failure, massive lymphadenopathy, or B-symptoms. Treatments include targeted agents (Ibrutinib - BTK inhibitor; Venetoclax - BCL2 inhibitor) or chemo-immunotherapy (e.g., Fludarabine, Cyclophosphamide, Rituximab - FCR, though rarely used now in the elderly). CML: First-line is a TKI (e.g., Imatinib, Nilotinib, or Dasatinib). These are oral agents taken daily. Monitoring of BCR-ABL transcript levels via qPCR is essential to assess response. Allogeneic stem cell transplant is reserved for TKI resistance or blast crisis.