Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia

1. Definition
   Chronic Myeloid Leukaemia (CML) is a clonal disorder of the hematopoietic stem cell in which there is uncontrolled proliferation of myeloid lineage cells. It usually progresses slowly and is most common in middle‑aged adults.

2. Synonyms
   Chronic Myelogenous Leukaemia – the term used in many textbooks, same disease.
   Chronic Granulocytic Leukaemia – older name emphasizing the granulocytic predominance.

3. Causes / Etiology

• Philadelphia chromosome (t(9;22)(q34;q11)) – creates the BCR‑ABL fusion gene that drives the disease. This abnormality is present in more than 90 % of cases.
• Radiation exposure – high‑dose ionising radiation can damage the marrow and increase risk. It is a less common but recognised factor.
• Chemical exposure (benzene, pesticides) – long‑term contact with certain chemicals has been linked to CML. The risk rises with cumulative exposure.

4. Types / Classification
   CML is classified into three clinical phases.

a) Chronic phase (CP) – the initial stage lasting on average 4‑6 years. The disease is relatively stable with a modest rise in white cells. Patients may be asymptomatic or have mild fatigue. This phase differs from an acute leukaemia by the low blast count (<10 %).

b) Accelerated phase (AP) – an intermediate stage lasting a few months. There is an increase in blast cells (10‑19 %) and worsening of symptoms such as bone pain and splenomegaly. The disease becomes more aggressive than the chronic phase but still not fully acute.

c) Blastic phase (BP) – the terminal stage, analogous to an acute leukaemia, with ≥20 % blasts in blood or marrow. Symptoms are severe, including high fever, profound anaemia and marrow failure. Survival without treatment is measured in weeks to months.

5. Pathophysiology / Pathology – step by step

6. A reciprocal translocation between chromosomes 9 and 22 creates the Philadelphia chromosome.

7. The BCR‑ABL fusion gene is formed and encodes a constitutively active tyrosine‑kinase.

8. This abnormal kinase continuously signals for cell division, preventing normal apoptosis.

9. Myeloid progenitor cells proliferate unchecked and accumulate in the bone marrow and peripheral blood.

10. Over time additional genetic hits allow progression from chronic to accelerated and blastic phases.
    The BCR‑ABL protein is the central driver of the disease, making it a target for therapy.

11. Clinical Features

General features (present in most phases) – fatigue, weight loss, night sweats, low‑grade fever. These are nonspecific but prompt further investigation.

Chronic phase – many patients are asymptomatic; if symptoms appear they are mild: early satiety from splenomegaly, mild anaemia‑related pallor, occasional bruising.

Accelerated phase – more pronounced splenomegaly, bone pain, increasing fatigue, occasional bleeding due to platelet dysfunction.

Blastic phase – severe anaemia, high‑grade fever, bleeding, infections, marked weight loss; the picture resembles acute leukaemia.

7. Complications

Acute complications – severe thrombocytopenia leading to bleeding, neutropenia predisposing to infections, tumour lysis syndrome after rapid cell kill. Prompt recognition can reduce mortality.

Chronic complications – massive splenomegaly causing abdominal discomfort, chronic anaemia, iron overload from repeated transfusions, progression to blast crisis. Regular monitoring helps to prevent irreversible damage.

8. Investigations / Diagnosis

Routine test – complete blood count showing marked leukocytosis with left‑shifted neutrophils and basophilia. This alerts the clinician to a myeloproliferative process.

Specific test – bone‑marrow aspiration and biopsy to assess cellularity, blast percentage and fibrosis. It confirms the phase of disease.

Confirmatory test – cytogenetic analysis (karyotype) for Philadelphia chromosome and quantitative PCR for BCR‑ABL transcript. These establish the diagnosis and provide a baseline for therapy monitoring.

9. Differential Diagnosis

• Essential thrombocythemia – presents with isolated thrombocytosis; lacks the BCR‑ABL fusion and basophilia seen in CML.
• Polycythemia vera – characterized by increased red cell mass and JAK2 mutation; splenomegaly may be present but leukocytosis pattern differs.
• Acute myeloid leukaemia – high blast count (>20 %) from the outset; CML in blast phase can mimic it but a prior chronic phase history and BCR‑ABL positivity help differentiate.

10. Management / Treatment

General management – regular clinical review, complete blood counts every 1‑3 months, and monitoring of BCR‑ABL transcript levels to assess response. Supportive care includes transfusions when needed and infection prophylaxis.

Modern medicine treatment – tyrosine‑kinase inhibitors (TKIs) are the cornerstone. Imatinib, dasatinib and nilotinib inhibit the BCR‑ABL kinase, leading to cytogenetic remission in most patients. Second‑line agents are used if resistance or intolerance occurs. Allogeneic stem‑cell transplantation remains an option for TKI‑refractory disease.

Diet and lifestyle advice – a balanced diet rich in fresh fruits, vegetables and adequate protein supports marrow health; avoid smoking and limit alcohol as they can impair liver metabolism of TKIs. Regular moderate exercise improves stamina and reduces treatment‑related fatigue.

11. Homeopathic Therapeutics – selected remedies

12. Arsenicum album
    • Causation – exposure to toxic substances or chronic exhaustion.
    • Characteristic symptoms – restlessness, burning pains, great thirst for cold water.
    • Modalities – symptoms worse at night, better with warm drinks.
    • Mental state – anxiety, fear of death, feeling of impending doom.
    • Thirst and appetite – intense thirst for cold water, appetite poor.
    • Discharges – thin, watery stools; scant urine.
    • Physical generals – emaciation, weakness of muscles, hyper‑sensitive skin.
    • Suitable constitution – individuals who are thin, chilly and highly anxious.
    • This remedy is thought to modulate the over‑active immune response seen in CML.

13. Carcinosin
    • Causation – hereditary predisposition or exposure to carcinogenic agents.
    • Characteristic symptoms – deep‑seated fatigue, weight loss despite good appetite.
    • Modalities – worse from mental exertion, better from rest.
    • Mental state – indifference, lack of interest, occasional melancholy.
    • Thirst and appetite – normal thirst, appetite may be slightly increased.
    • Discharges – occasional blood‑stained sputum, mild diarrhoea.
    • Physical generals – enlarged spleen, palpable lymph nodes, pallor.
    • Suitable constitution – patients with a family history of malignancy.
    • It is used to address the underlying malignant tendency in the marrow.

14. Phytolacca
    • Causation – chronic infection or inflammation of the lymphatic system.
    • Characteristic symptoms – swollen, painful glands, sore throat, feeling of a lump in the throat.
    • Modalities – worse on swallowing, better with warm fluids.
    • Mental state – irritability, desire to be alone.
    • Thirst and appetite – thirst for cold water, appetite reduced.
    • Discharges – thick, yellowish mucus, occasional blood‑streaked saliva.
    • Physical generals – marked splenomegaly, bruising easily.
    • Suitable constitution – individuals who are hot‑flushy and have a history of recurrent infections.
    • Helps to reduce lymphoid over‑growth and spleen enlargement.

15. Lycopodium
    • Causation – over‑work, emotional suppression, and poor digestion.
    • Characteristic symptoms – bloating, flatulence, early satiety.
    • Modalities – worse in the evening, better after a light walk.
    • Mental state – lack of confidence, fear of failure.
    • Thirst and appetite – thirst for warm drinks, appetite variable.
    • Discharges – loose, foul‑smelling stools.
    • Physical generals – weak liver, low‑grade fever, enlarged spleen.
    • Suitable constitution – people who are ambitious yet insecure.
    • It is selected to improve digestive function and support the liver‑spleen axis.

16. Natrum Muriaticum
    • Causation – prolonged grief, emotional suppression, exposure to salty foods.
    • Characteristic symptoms – dry, cracked lips, watery nasal discharge.
    • Modalities – worse from heat, better in cool fresh air.
    • Mental state – melancholy, tendency to dwell on past hurts.
    • Thirst and appetite – thirst for small sips of water, appetite moderate.
    • Discharges – clear, watery nasal secretions, occasional mild diarrhoea.
    • Physical generals – thin, dry skin, tendency to bruising.
    • Suitable constitution – individuals who are introverted and keep emotions inside.
    • Aims to restore fluid balance and emotional equilibrium.

17. Calcarea carbonica
    • Causation – chronic damp exposure, over‑exertion in cold environments.
    • Characteristic symptoms – profuse sweating, especially at night.
    • Modalities – worse from cold, damp, better from warmth.
    • Mental state – fear of heights, lack of confidence in decision‑making.
    • Thirst and appetite – increased appetite, thirst for cold water.
    • Discharges – thick, mucous sputum, occasional constipation.
    • Physical generals – sluggish metabolism, enlarged spleen, bone tenderness.
    • Suitable constitution – stout, slow‑moving individuals who feel chilly.
    • Used to strengthen the skeletal and marrow framework.

18. Sulphur
    • Causation – chronic irritation of the skin and mucous membranes, exposure to pollutants.
    • Characteristic symptoms – itching, burning sensations, especially after a warm bath.
    • Modalities – worse from heat, better from cool fresh air.
    • Mental state – restless, impatient, tendency to argue.
    • Thirst and appetite – great thirst for cold water, appetite large.
    • Discharges – thin, watery diarrhoea, occasional foul‑smelling urine.
    • Physical generals – reddened skin, enlarged lymph nodes, mild anaemia.
    • Suitable constitution – people who are intellectual, often overheated.
    • Helps to detoxify the blood and reduce inflammatory skin manifestations.

19. Nux vomica
    • Causation – over‑indulgence in stimulants (caffeine, alcohol) and irregular lifestyle.
    • Characteristic symptoms – irritability, headache, feeling of heaviness in the head.
    • Modalities – worse after midnight meals, better after a light walk.
    • Mental state – impatient, easily angered, desire for control.
    • Thirst and appetite – thirst for hot drinks, appetite strong but irregular.
    • Discharges – thick, yellowish mucus, occasional constipation.
    • Physical generals – hypertension, liver congestion, mild splenomegaly.
    • Suitable constitution – ambitious, work‑driven individuals with poor sleep.
    • Intended to correct metabolic excesses and improve liver function.

20. Prognosis
    If diagnosed in the chronic phase and treated promptly with TKIs, long‑term survival approaches that of the general population. Poor prognosis is associated with presentation in blast phase, high BCR‑ABL transcript levels, or resistance to therapy. Early molecular response is a key predictor of favourable outcome.

21. Prevention
    There is no specific primary prevention for CML, but avoidance of known risk factors such as high‑dose radiation and prolonged exposure to benzene reduces risk. Regular health check‑ups enable early detection, which markedly improves therapeutic success.

22. Diet

Recommended foods – fresh fruits, green leafy vegetables, whole grains and lean protein; these provide antioxidants and support marrow health.

Avoided foods – processed meats, excessive sugary drinks and alcohol; they can impair liver metabolism of TKIs and increase oxidative stress.

These notes are written in a simple, handwritten‑style language suitable for MUHS BHMS examination preparation.