AKT · Haematology/Haemato-oncologylow yield

Chronic leukaemia (CLL & CML)

Clonal proliferation of mature lymphocytes (CLL) or myeloid cells (CML, BCR-ABL/Philadelphia)

Overview

Indolent leukaemias of MATURE cells, often found incidentally on a routine FBC. Chronic lymphocytic leukaemia (CLL) is a clonal expansion of mature B-lymphocytes (lymphocytosis, smear/smudge cells) in older adults. Chronic myeloid leukaemia (CML) is a myeloproliferative disorder with the Philadelphia chromosome (BCR-ABL, t(9;22)) causing a raised neutrophil/myeloid count and massive splenomegaly, transformed by targeted tyrosine kinase inhibitors.

Recognise

CLL: often asymptomatic incidental LYMPHOCYTOSIS in an older adult; lymphadenopathy, hepatosplenomegaly; SMEAR (smudge) cells on film; can cause autoimmune haemolysis and recurrent infections
CML: raised WCC with the whole myeloid series, MASSIVE splenomegaly, hypermetabolic symptoms; PHILADELPHIA chromosome (BCR-ABL, t(9;22)); can transform to blast crisis
CLL complications: Richter transformation (to aggressive lymphoma), autoimmune haemolytic anaemia, hypogammaglobulinaemia (infections)

Red flags

CLL with rapidly enlarging node/systemic symptoms → Richter transformation
CML blast crisis (rising blasts) → transformation to acute leukaemia

Differentials & how to tell them apart

Acute leukaemiablasts + rapid marrow failure — chronic leukaemias are mature-cell and indolent

Reactive lymphocytosisinfection (viral) — polyclonal, resolves; CLL is monoclonal on flow

Other myeloproliferative neoplasmspolycythaemia vera/ET/myelofibrosis — JAK2; CML has BCR-ABL

CLL — lymphocytosis with smear (smudge) cells (blood film)
Prof. Erhabor Osaro / CC BY-SA 4.0 — Wikimedia Commons

Investigations

FBC (lymphocytosis in CLL; neutrophilia/myeloid in CML), blood FILM (smear cells in CLL); CLL — immunophenotyping (flow cytometry) for clonal B-cells; CML — BCR-ABL/Philadelphia chromosome (cytogenetics/molecular); marrow/imaging for staging.

Management

CLL → watch-and-wait then targeted therapy if progressive; CML → tyrosine kinase inhibitor (imatinib)

1Distinguish CLL (mature lymphocytosis + smear cells, confirm with flow cytometry) from CML (myeloid proliferation + massive splenomegaly + BCR-ABL/Philadelphia chromosome). Early asymptomatic CLL → watch-and-wait.Gate: CML is defined by the Philadelphia chromosome (BCR-ABL) and treated with a tyrosine kinase inhibitor (imatinib); a rapidly enlarging node in CLL suggests Richter transformation.
2CLL active disease → chemo-immunotherapy/targeted agents (BTK inhibitor/venetoclax), manage autoimmune haemolysis/infections; CML → imatinib, transplant for transformation.

CLL: watch-and-wait if asymptomatic/early — many never need treatment; treat for symptomatic/progressive disease

CLL active disease: chemo-immunotherapy / targeted agents (BTK inhibitors, venetoclax) — by stage/genetics; manage autoimmune haemolysis and infections (immunoglobulin)

CML: tyrosine kinase inhibitor (imatinib) — targets BCR-ABL — transformed prognosis to near-normal life expectancy

Stem-cell transplant — selected/transformed disease

Key points

Incidental mature LYMPHOCYTOSIS + smear cells in an older adult = CLL (flow cytometry; watch-and-wait if early; Richter transformation, autoimmune haemolysis). Myeloid proliferation + MASSIVE splenomegaly + PHILADELPHIA chromosome (BCR-ABL) = CML → tyrosine kinase inhibitor (imatinib).

Monitor & prognosis

Counts/lymphocyte doubling time (CLL), BCR-ABL response (CML), transformation, infection.

CLL often indolent (many never treated); CML transformed by TKIs to near-normal life expectancy.

Source: BSH CLL/CML