Makindo Medical Notes

Related Subjects: |Hypercalcaemia |Multiple Myeloma |Extramedullary Plasmacytoma |Smouldering Myeloma |MGUS |Waldenstrom Macroglobulinaemia |Oncological emergencies

Myeloma should be considered in any patient presenting with bone pain, raised calcium, or a high ESR.

About

• A malignant tumour of plasma cells, which originate from the B cell lineage.
• May produce monoclonal immunoglobulins, such as IgG, IgA, or light chains.
• Median survival is approximately 2-3 years.

Incidence

• More common in men than women.
• Incidence: 5.4 per 100,000 per year.
• Approximately 5,500 new cases per year in the UK.

Stages of Progression

Note: Treatment is not indicated for patients with MGUS. Randomized trials have demonstrated no benefit from early intervention, and simple monitoring of paraproteins with clinical review is all that is required.

Aetiology

• Uncontrolled proliferation of a single clone of plasma cells.
• Tumour cells within the bone marrow lead to bone destruction and cytopenia.
• Immunodeficiency occurs due to suppression of normal immune functions.
• Myeloma proteins cause hyperviscosity and can lead to amyloidosis.
• Multifactorial renal failure is common due to nephrotoxic effects.
• Anaemia results from marrow infiltration and renal insufficiency.

Plasma cell secretions activate osteoclasts, leading to bone lysis, pathological fractures, neurologic impairment, and hypercalcaemia (exacerbated by impaired renal function).

Epidemiology

• Twice as common in individuals of African descent.
• May develop in 1% of individuals with MGUS.

Differing Manifestations

Clinical Features

• Most patients are over 60 years old.
• More common in males than females.
• Bone pain due to lytic lesions and osteoporotic fractures.
• Pathological fractures and spinal cord compression may occur.
• Renal failure, often due to toxic effects of Bence–Jones proteins (light chains).
• Increased risk of infections due to immunoparesis (hypogammaglobulinaemia).
• Pancytopenia caused by bone marrow failure.
• Symptoms of hypercalcaemia (fatigue, confusion, constipation).

AL Amyloid Symptoms

• Amyloid may cause peripheral neuropathy, restrictive cardiomyopathy, nephrotic syndrome, and severe fatigue.
• Carpal tunnel syndrome, diarrhoea (possibly with blood), enlarged tongue, and cardiac arrhythmias may also be present.
• Hyperviscosity syndrome may occur, leading to dizziness, altered vision, and haemorrhage. Associated with IgA myeloma.

Investigations

• FBC: Anaemia, low platelets, and low WCC.
• Blood tests: Raised ESR, CRP, LDH, urate, and hypercalcaemia.
• Renal function tests: Impaired in 50% due to the toxicity of light chains (BJP).
• Serum protein electrophoresis and urine for Bence–Jones protein.
• Bone marrow biopsy for plasma cells and molecular testing (FISH).
• Radiology: Whole-body MRI, CT, and PET-CT for soft tissue plasmacytomas.

CRAB Mnemonic

• Hypercalcaemia: Corrected Ca²⁺ >2.75mmol/L.
• Renal impairment: CrCl <40, Cr >177.
• Anaemia: Hb <100g/L or 20g below normal.
• Bone lesions: Lytic lesions or osteoporosis.

Complications

• Pathologic fractures.
• Hypercalcaemia.
• Renal failure.
• Recurrent infections.
• Anaemia.
• Spinal cord compression in 10% of patients.

Beta-2 microglobulin is a useful marker of prognosis — raised levels indicate a poor prognosis. Low albumin is also associated with a poor prognosis.

Management

• For younger and fit patients: Velcade (Bortezomib), Thalidomide, and Dexamethasone regimens. Autologous stem cell transplantation (ASCT) is the standard of care in remission.
• Supportive treatments: Blood transfusions for anaemia, IV Pamidronate for bone pain, and rehydration for hypercalcaemia.
• Orthopaedic referral for kyphoplasty for vertebral fractures.
• NSAIDs for pain management (monitor renal function).
• Plasma exchange for hyperviscosity syndrome.
• Allopurinol for hyperuricaemia.
• Radiotherapy for bone lesions and pain relief.
• Discussions with patients and families for emotional support and palliative care.

References

• Guidelines for the management of Multiple Myeloma