Chronic Lymphocytic Leukaemia

Overview

CLL and SLL = SAME monoclonal B-cell neoplasm, presenting as leukaemia (CLL) or nodal lymphoma (SLL). ~9% of lymphoid neoplasms. CLL = most common lymphoid leukaemia. Age >50yr, male 2:1.

Clinical features

May be asymptomatic or insidious:

• Anaemia (weakness, fatigue, dyspnoea)
• Symmetric, discrete, non-tender lymphadenopathy — very common
• Splenomegaly + hepatomegaly — usual
• Bleeding (if thrombocytopenia)
• ↑Infection risk (esp. respiratory) — hypogammaglobulinaemia
• Less common: mediastinal pressure, tonsillar enlargement, visual changes, bone/joint pain

Labs

Blood: mild-mod normocytic normochromic anaemia (~20% develop Coombs’+ AIHA). Marked leucocytosis but LESS than CML (50-200k). >90% mature small lymphocytes. Smudge/basket cells (fragile degenerated nuclei). Neutrophils normal until advanced. Platelets normal/mild↓.

Marrow: ↑lymphocytes (25-95%), ↓myeloid+erythroid precursors.

Lymph node biopsy: diffuse small uniform lymphocytes, no atypia/mitoses, monoclonal, mantle-zone phenotype.

Special tests: mouse RBC rosette test +ve >95% (confirms monoclonal B-cell) · CD5+ (unusual for B cell — key finding!) + CD19,20,23 + monoclonal light chain (κ/λ) · ↓serum Ig · Coombs’ +ve 20% · trisomy 12 in ~25% (most common cytogenetic abnormality).

Treatment/prognosis

CANNOT be eradicated (unlike other leukaemias) — palliative/symptomatic only: alkylating agents (chlorambucil, cyclophosphamide), steroids, radiotherapy. Splenectomy — specifically for CLL+AIHA complication.

Better prognosis than CML (blastic transformation rare). Staged:

• Stage A: lymphocytosis ± limited nodes — good, median survival >10yr
• Stage B: lymphocytosis + significant nodes + hepatosplenomegaly — intermediate

Clinical relevance

CD5+ on B cells = distinctive (CD5 normally T-cell marker) — key diagnostic immunophenotype point. Low blastic transformation + indolent course (vs CML) = why managed palliatively not curatively. AIHA = treatable CLL complication (splenectomy targets THIS, not the leukaemia). Symmetric painless lymphadenopathy + small mature lymphocytosis (not blasts) = suspect CLL over acute leukaemia/reactive lymphocytosis on initial film review.

Overview

Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) are the same monoclonal B-cell neoplasm presenting either as leukaemia (CLL) or as a nodal lymphoma (SLL) — together constituting about 9% of lymphoid neoplasms. As a leukaemia, CLL is the most common lymphoid leukaemia; as a lymphoma, SLL makes up about 7% of NHL. Occurs predominantly in middle/older age (>50 years), with a male predominance (2:1).

Clinical Features

May be asymptomatic (incidental finding on routine blood count) or present insidiously with non-specific features:

• Anaemia — gradual weakness, fatigue, dyspnoea.
• Symmetric, discrete, non-tender superficial lymphadenopathy — a very common finding.
• Splenomegaly and hepatomegaly — usual.
• Haemorrhagic manifestations — where thrombocytopenia is present.
• Increased infection susceptibility, particularly respiratory tract — from hypogammaglobulinaemia and functional immune impairment.
• Less common: mediastinal pressure, tonsillar enlargement, visual disturbance, bone/joint pain.

Laboratory and Morphologic Findings

Diagnosis is usually achievable from physical findings plus blood smear alone.

Blood picture: mild-moderate normocytic normochromic anaemia (mild reticulocytosis may occur; ~20% develop Coombs’-positive autoimmune haemolytic anaemia); marked leucocytosis, though less than CML (50,000–200,000/µL), with >90% mature small lymphocytes; characteristic smudge/basket cells (degenerated forms from fragile malignant lymphocyte nuclei); neutrophil count usually normal until advanced disease; platelets normal or mildly reduced (autoimmune mechanism).

Bone marrow: increased lymphocytes (25–95%), reduced myeloid and erythroid precursors.

Lymph node biopsy (if lymphadenopathy present): diffuse replacement by well-differentiated, mature, uniform small lymphocytes without atypia or significant mitotic activity — monoclonal B cells with mantle-zone immunophenotype.

Immunophenotyping/special tests:

• Erythrocyte rosette test with mouse red cells positive in >95% — confirms monoclonal B-cell origin.
• B-cell markers: characteristically CD5-positive (unusual for B cells, normally a T-cell marker — a key diagnostic feature), plus pan-B markers CD19, CD20, CD23, surface immunoglobulin with monoclonal light-chain restriction (κ or λ).
• Serum immunoglobulin levels generally reduced.
• Coombs’ test positive in 20%.
• Cytogenetics: trisomy 12 in ~25% (most common recurrent abnormality).

Treatment and Prognosis

Unlike other leukaemias, CLL cannot be eradicated by available drugs or radiotherapy to achieve true complete remission — treatment is palliative/symptomatic: alkylating agents (chlorambucil, cyclophosphamide), corticosteroids, radiotherapy. Splenectomy is indicated specifically for CLL complicated by autoimmune haemolytic anaemia.

Prognosis is generally better than CML, since blastic transformation is rare, and correlates with clinical stage:

• Stage A — lymphocytosis alone or with limited lymphadenopathy; good prognosis (median survival >10 years).
• Stage B — lymphocytosis with significant lymphadenopathy and hepatosplenomegaly; intermediate prognosis.
• (Further staging incorporates anaemia and thrombocytopenia as markers of more advanced, marrow-replacing disease.)

Clinical Relevance

• CD5 positivity on a B-cell population is a genuinely distinctive immunophenotypic finding worth remembering specifically — CD5 is otherwise a T-cell marker, and its aberrant expression on CLL’s malignant B cells is a key piece of the diagnostic immunophenotype (alongside CD19/20/23 and light-chain restriction).
• The <10% blastic transformation rate and generally indolent course, in sharp contrast to CML’s much higher and more clinically threatening blast crisis rate, is the reason CLL is managed palliatively rather than with curative intent from diagnosis — a genuinely different treatment philosophy from other leukaemias covered elsewhere in this section.
• Recognising autoimmune haemolytic anaemia as a treatable complication of CLL (rather than a separate diagnosis) matters clinically, since splenectomy specifically targets this complication rather than the underlying leukaemia itself.
• The symmetric, painless lymphadenopathy pattern combined with marked lymphocytosis of small mature-looking lymphocytes (not blasts) is what should prompt suspicion of CLL over an acute leukaemia or reactive lymphocytosis on initial blood film review, before immunophenotyping confirms the diagnosis.

No Rendered Diagram for This Topic

CLL is a classification-and-features topic (clinical presentation, blood/marrow findings, immunophenotype, staging) rather than a multi-step pathogenic mechanism the sources describe in stages — the underlying lesion is simply monoclonal expansion of a mature-appearing B-cell population, not a cascade that benefits from a flowchart beyond what the lists and staging summary in notes.md already communicate.

Hand-draw suggestion (optional, not a rendered requirement): a short immunophenotype checklist (CD5+, CD19+, CD20+, CD23+, monoclonal light chain) alongside the two-stage prognosis summary (Stage A vs Stage B) is the most efficient hand-drawn revision aid for this topic.