GeriQBank · Paper III · Q4
Chronic Myeloid Leukaemia — Clinical Features & Management
- Chapter
- Haematology
- Years asked
- Not recorded in the source
- Frequency
- Not set in Papers III–IV, 2009–2025
Detailed answer
Pro · free in betaAttempt it firstOutline your answer before revealing it — definition, causes, evaluation, management and the geriatric angle.Reveal answer
Textbook gap: Pathy's mentions CML only once — Ch. 24, Table 24.2 — as a myeloproliferative disorder causing acquired platelet dysfunction (bleeding paradoxically more common when platelets >10,00,000/µL). Everything else is externally sourced (ELN 2025, WHO-HAEM5).
High-Yield Points
A. Definition & Epidemiology
Myeloproliferative neoplasm defined by Philadelphia chromosome t(9;22) → BCR::ABL1 fusion, a constitutively active tyrosine kinase.
~15% of adult leukaemias. Indian series show younger median age (30s–40s) with bulkier/more advanced disease at diagnosis.
TKIs reduced annual mortality from 10–20% to ~1%; 10-yr survival now 82–87%; prevalence rising steeply.
B. Clinical Features
Nearly half asymptomatic — found on routine leucocytosis.
Constitutional symptoms: fatigue, weight loss, low-grade fever, night sweats.
Splenomegaly is the most consistent sign, may be massive; splenic infarction causes sudden pleuritic pain with rub.
Significant lymphadenopathy is rare in chronic phase — suggests blast phase if present.
Leukostasis at WCC >1,00,000/µL — priapism, blurred vision, tinnitus, confusion, stroke (emergency).
Hyperuricaemia/gout; characteristically high serum B12.
Blood picture: leucocytosis with full left shift, "myelocyte bulge", basophilia (near-universal clue), eosinophilia, thrombocytosis, low LAP score.
C. Phases, Diagnosis & Management
WHO 2022 abolished "accelerated phase"; blast phase = ≥20% blasts (older ELN definition was >30%).
Diagnosis: marrow morphology + cytogenetics + RT-PCR (transcript type e13a2/e14a2) for additional chromosomal abnormalities.
ELTS score replaces Sokal/Euro/EUTOS for prognosis.
Initial management: hydroxyurea, hydration, allopurinol, then start TKI once diagnosis confirmed.
Six first-line TKIs: imatinib, dasatinib, nilotinib, bosutinib, asciminib (2024), radotinib. Generic imatinib remains most cost-effective in India.
Monitoring: RT-qPCR (International Scale) 3-monthly. Milestones: BCR::ABL1(IS) ≤10% at 3mo, ≤1% at 6mo, ≤0.1%(MMR) at 12mo.
Response Milestones
Response Definition
Complete cytogenetic (CCyR) No Ph+ metaphases ≈ BCR::ABL1(IS) ≤1% Major molecular (MMR/MR3) BCR::ABL1(IS) ≤0.1% MR4 / MR4.5 ≤0.01% / ≤0.0032% Treatment Algorithm Situation Approach Toxicity in responder Reduce dose rather than switch drugs Resistance Check adherence/interactions first, then BCR::ABL1 kinase mutation analysis Second line After imatinib → any 2GTKI. After 2GTKI → ponatinib or asciminib T315I mutation Ponatinib, high-dose asciminib, or olverembatinib Blast phase Intensive chemo + potent TKI → allogeneic SCT MD Geriatrics – Haematology Compendium Page 9 of 34 Allo-SCT Resistance to ponatinib/asciminib; RIC and haploidentical donors widen access in elderly Latest Updates (2023–Present)
WHO-HAEM5 abolished accelerated phase; blast phase = ≥20%. Asciminib (STAMP inhibitor, binds myristoyl pocket) — ASC4FIRST (NEJM 2024): MMR at 48wk 67.7% vs 49% with investigator-chosen TKI; FDA-approved first-line 2024. ELN 2025 renamed milestones "favourable/warning/unfavourable" (no switch on a single PCR result). Older/comorbid patients: "failed" milestones still had ~80% 10-yr survival (German CML-IV, MDACC) — more conservative approach supported, but not based on age alone. Dose reduction preferred over switching for toxicity — low-dose dasatinib 50mg or 20mg (DAVLEC, age ≥70) reduces effusions. EURO-SKI final analysis (JCO 2024): MMR maintained in 46% at 12 months after stopping TKI (TFR). Olverembatinib effective after ponatinib/asciminib failure. EBMT: transplant outcome determined by disease stage/Karnofsky score, not number of prior TKI lines — haploidentical donors and RIC have widened access in the elderly.
Current Practice Update
Domain Pathy's (2022) Current evidence
Coverage One line — platelet dysfunction only Comprehensive ELN 2025/WHO-HAEM5 Disease phases Not addressed Biphasic; blast phase ≥20%; accelerated phase abolished First-line therapy Not addressed Six TKIs; asciminib added first-line 2024 Toxicity management Not addressed Dose reduction preferred over switching Older patients Endorses CGA generally ELN 2025 advises individualised, often conservative management MD Geriatrics – Haematology Compendium Page 10 of 34
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References
- PAPERS-2-3-4_COMBINED.pdf — page 848
- GeriQBank source PDF — p. 848
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