Haemato-oncology

Question 1

What is the definition and epidemiology of Multiple Myeloma?

Answer 1

Multiple myeloma is a haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and production of monoclonal immunoglobulin (paraprotein, usually IgG or IgA).

• Second most common haematological malignancy, peak incidence in 70-year olds. Afro-Caribbeans > White people > Asians.

Question 2

What are the clinical features of Multiple Myeloma?

Answer 2

Patients usually complain/present with:

• Bone pain (especially backache) resulting from vertebral collapse and pathological fractures if severe. This is because of high serum levels of RANKL produced by plasma cells and bone marrow stroma, activating osteoclast activation.
• Features of anaemia such as lethargy, weakness, pallor.
• Recurrent infections related to deficient antibody production (relative hypogammaglobinaemia - due to high levels of paraprotein inhibiting production of useful antibodies), abnormal cell-mediated immunity and neutropenia.
• Features of renal failure and/or hypercalcaemia such as polydipsia, polyuria, anorexia, vomiting, constipation and mental disturbance. Tachycardia and dehydration can be examination findings.
• Amyloidosis occurs in 5%
• In 2% there are symptoms of hyperviscosity, such as visual disturbance, headaches, bleeding.

Can be remembered as CRAB symptoms. (Calcium, Renal, Anaemia, Bone).

Other examination findings include purpura, hepatosplenomegaly, macroglossia, carpel tunnel syndrome (due to amyloidosis) and peripheral neuropathies.

Question 3

What are the investigations for Multiple Myeloma?

Answer 3

Bloods:

• Presence of paraprotein (M protein) in serum - mainly IgG and IgA.
• Elevated serum immunoglobulin-free light chains (light chains synthesised by plasma cells and unpaired with heavy chains).
• FBC ↓Hb, normocytic normochromic
• ↑ESR and CRP
• U&Es (↑creatinine, ↑Ca2+, in 45%).
• Presence of paraprotein in urine (Bence Jones protein).

Radiological investigations of skeleton (chest, pelvic and/or vertebral) looking osteolytic lesions without surrounding sclerosis. Historically done by X-ray, but increasingly done by MRI as recommended by NICE.

An X-ray may show a ‘rain-drop skull’ (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - ‘pepperpot skull’.

Bone marrow aspirate and trephine showing ↑plasma cells. Also allows for cytogenetics and FISH analysis.

Question 4

Describe the management of Multiple Myeloma

Answer 4

Asymptomatic patients: watch and wait, unless patients have ≥ 60% clonal cells, excessive free light chains or ≥ 1 bone lesion.

Symptomatic patients:

• HSCT eligible : induction therapy followed by autologous HSCT
• HSCT ineligible: chemotherapy alone (e.g., dexamethasone and lenalidomide)

High-risk patients should be enrolled in clinical trials

Supportive therapy

• Osteolysis and bone pain - bisphosphonates, radiation therapy of osteolytic regions
• Pancytopenia with anaemia and increased risk of infection - blood transfusions, Granulocyte-colony stimulating factor (G-CSF) and erythropoietin (EPO).