Chronic Leukaemia and Myeloid Neoplasms

The answer first

The chronic leukaemias and their related myeloid neoplasms are the indolent clonal disorders of haematopoiesis. Two diseases dominate: chronic lymphocytic leukaemia (CLL) — the commonest leukaemia in the Western world, a clonal B-cell disorder whose management turns on a single principle — and chronic myeloid leukaemia (CML) — the archetypal molecular cancer, defined by the BCR-ABL1 fusion of the Philadelphia chromosome t(9;22) and transformed by tyrosine kinase inhibitors. The myeloproliferative neoplasms (polycythaemia vera, essential thrombocythaemia, myelofibrosis) and the myelodysplastic syndromes complete the family. ^[1]

Two organising principles carry the whole topic: ^[1]

1. CLL turns on active versus inactive disease, not on the lymphocyte count. Asymptomatic early-stage CLL is observed (watch and wait) because early treatment confers no survival advantage; therapy is reserved for the iwCLL-defined active disease criteria ^[10].
2. CML turns on the BCR-ABL1 transcript level. Diagnosis, response assessment, resistance detection and the decision to stop therapy are all read off the quantitative PCR for BCR-ABL1 on the International Scale.

The treatment ladders: ^[1]

• CLL — watch and wait if asymptomatic; for active disease, chemoimmunotherapy (FCR for fit patients with favourable biology, BR for less fit) or a novel agent (ibrutinib, venetoclax with obinutuzumab) for adverse biology or frailty ^[7][8][9].
• CML — first-line tyrosine kinase inhibitor (imatinib, dasatinib, nilotinib, bosutinib), monitored by serial BCR-ABL1 transcript levels; ponatinib for the T315I mutation; allogeneic transplant only for TKI failure ^[1][4][5].
• MPN — risk-stratified cytoreduction (phlebotomy and aspirin for polycythaemia vera, hydroxycarbamide or anagrelide for essential thrombocythaemia, ruxolitinib for myelofibrosis).
• MDS — risk-stratified by the IPSS-R: supportive care, erythropoiesis-stimulating agents, luspatercept and lenalidomide for lower-risk; azacitidine and transplant for higher-risk ^{[14][15][16][17]}.

DWE high-yield: The answer to almost every chronic leukaemia question is "stage or risk-stratify the patient, then treat by fitness and molecular biology." Asymptomatic early CLL is watched. Active CLL gets FCR or BR (fit) or ibrutinib/venetoclax (adverse biology or frail). CML gets a TKI monitored by BCR-ABL1 qPCR. The T315I mutation needs ponatinib. Never treat an asymptomatic patient with early CLL. ^[1]

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References17ShowHide

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