Pathology
Haematology
Regarding chronic myeloid leukaemia, which of the following statements is CORRECT:
Answer:
Chronic myeloid leukaemia (CML) is a clonal disorder of a pluripotent stem cell. The disease accounts for around 15% of leukaemias and may occur at any age. The diagnosis of CML is rarely difficult and is assisted by the characteristic presence of the Philadelphia (ph) chromosome. This disease occurs in either sex, most frequently between the ages of 40 and 60 years. In up to 50% of cases the diagnosis is made incidentally from a routine blood count. Leucocytosis is the main feature, with a complete spectrum of myeloid cells seen in the peripheral blood. The levels of neutrophils and myelocytes exceed those of blast cells and promyelocytes.Increased circulating basophils are a characteristic feature. Normochromic normocytic anaemia is usual. Platelet count may be increased (most frequently), normal or decreased. The clinical outlook is very good and 90% of patients can expect long-term control of disease.Chronic Leukaemia
Pathology / Haematology / Malignancy
Last Updated: 25th April 2019
The leukaemias are a group of disorders characterised by the accumulation of malignant clonal white cells in the bone marrow and blood.
The chronic leukaemias are distinguished from acute leukaemias from their slower progression. Chronic leukaemias can be broadly subdivided into myeloid and lymphoid groups.
Chronic Myeloid Leukaemia
Incidence:
Chronic myeloid leukaemia (CML) is a clonal disorder of a pluripotent stem cell. The disease accounts for around 15% of leukaemias and may occur at any age. The diagnosis of CML is rarely difficult and is assisted by the characteristic presence of the Philadelphia (ph) chromosome. This disease occurs in either sex, most frequently between the ages of 40 and 60 years. However, it may occur in children and neonates, and in the very elderly. There is a genetic predisposition to development of the disease.
Clinical Features:
In up to 50% of cases the diagnosis is made incidentally from a routine blood count. In those cases where the disease presents clinically, the following features may be seen:
- Symptoms related to hypermetabolism
- weight loss
- lethargy
- anorexia
- night sweats
- Splenomegaly
- Features of anaemia
- pallor
- dyspnoea
- tachycardia
- Features of abnormal platelet function
- bruising
- epistaxis
- menorrhagia
- haemorrhage
- Gout or renal impairment caused by hyperuricaemia from excessive purine breakdown
- Visual disturbance and priapism (rare)
Investigations:
- Leucocytosis is the main feature, with a complete spectrum of myeloid cells seen in the peripheral blood. The levels of neutrophils and myelocytes exceed those of blast cells and promyelocytes.
- Increased circulating basophils are a characteristic feature.
- Normochromic normocytic anaemia is usual.
- Platelet count may be increased (most frequently), normal or decreased.
- Bone marrow is hypercellular with granulopoietic predominance.
- Serum uric acid is usually raised.
- Ph chromosome on cytogenetic analysis (98% of cases)
Management
- Tyrosine kinase inhibitors (TKI) are the mainstay of treatment and several different drugs are now available, largely replacing chemotherapy treatment
- Allogeneic stem cell transplantation is a potentially curative treatment for CML but because of the risks associated with the procedure, it is usually reserved for TKI failures or patient's presenting in accelerated phases.
Prognosis:
The clinical outlook is very good and 90% of patients can expect long-term control of disease.
Chronic Lymphocytic Leukaemia
Incidence:
Chronic lymphocytic leukaemia (CLL) is the most common of the chronic lymphoid leukaemias and has a peak incidence between 60 and 80 years of age. It is the most common form of leukaemia within Europe and the USA but less frequent elsewhere. The CLL tumour cell is a mature B-cell with weak surface expression of immunoglobulin (IgM or IgD). CLL cells typically exhibit impaired apoptosis and a prolonged lifespan, and this is reflected in their accumulation in the blood, bone marrow, liver, spleen and lymph nodes. The mean age at diagnosis is 72 years, with only 15% of cases before 50 years of age. The male: female ratio is approximately 2:1.
Clinical Features
- Over 80% of cases are diagnosed from the results of a routine blood test, usually taken for another reason.
- Enlargement of cervical, axillary or inguinal lymph nodes is the most frequent clinical sign.
- Features of anaemia and thrombocytopenia may be present
- Splenomegaly and, less commonly, hepatomegaly are common in later stages
- Immunosuppression is often a significant problem with recurrent infection
Investigations:
- Lymphocytosis
- CLL tumour cells
- Normochromic normocytic anaemia
- Thrombocytopenia
- Bone marrow aspiration shows up to 95% lymphocytic replacement of normal marrow elements
- Reduced concentrations of serum immunoglobulins are found
- Autoimmunity directed against cells of the haemopoietic system is common
Management:
It is very difficult to cure CLL and so the approach to therapy is generally conservative, aiming for symptom control rather than a normal blood count. Indeed, chemotherapy given too early in the disease can shorten rather than prolong life expectancy. Many patients never need treatment but treatment may be given for troublesome symptoms or if the lymphocyte count rises rapidly. Use of chemotherapy and an anti-CD20 monoclonal antibody establishes disease remission but is not curative.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
