Makindo Medical Notes.com

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

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

About

• A malignant tumour of plasma cells which are formed from B cell lineage
• May produce a monoclonal immunoglobulin e.g. IgG, IgA or light chains
• Median survival of 2-3 years.

Incidence

• Men > Women Incidence 5.4 per 100,000 per year
• 5,500 new cases per year in the UK

Stages of Progression

Aetiology

• Uncontrolled proliferation of a single clone of plasma cells
• Tumour cells within marrow lead to bone destruction and cytopenia.
• Immunodeficiency develops secondary to suppression of normal immune functions
• Myeloma proteins lead to hyperviscosity and amyloidosis.
• Multifactorial renal failure
• Anaemia due to marrow infiltration and renal insufficiency

Plasma cell secretions activate osteoclasts, leading to Bone lysis, pathologic fractures, and neurologic impairment and hypercalcemia (exacerbated by impaired renal function

Epidemiology

• Twice as common in Blacks
• May develop from 1% of those with MGUS

Plasma Cells

Clinical

• Most patients are over 60
• Commoner in Males > Females
• Bone pain due to lytic lesions and osteoporotic fractures
• Pathological fractures and even cord compression
• Renal failure - toxic effect of the Bence Jones Proteins (light chains)
• Infections due to immunoparesis (hypogammaglobulinaemia)
• Pancytopenia due to bone marrow failure
• Hypercalcaemia symptoms

AL Amyloid symptoms

• Amyloid - peripheral neuropathy, restrictive cardiomyopathy, diarrhoea, renal failure, severe fatigue, nephrotic syndrome with ankle, swelling, shortness of breath
• Carpal tunnel syndrome, diarrhoea (possibly with blood)or constipation, an enlarged tongue, difficulty swallowing, easy bruising, unusual rash, purplish patches around the eyes or cardiac arrhythmias.
• Hyperviscosity syndrome - dizziness, altered vision, haemorrhage, cardiac failure. Associated with IgA myeloma which dimerizes

Investigations

• FBC Anaemia, low platelets (bad sign), low WCC Leukoerythroblastic picture
• Check PT, APTT, TT, Fibrinogen
• ESR: raised to levels such as 100 mm/hr and there is hyperviscosity and rouleaux formation
• Check CRP: infection. Check LDH, Urate
• Ca/P/ALP/LFT/Bone profile: Hypercalcaemia - osteolytic "punched out" bone lesions on skeletal survey leads to fractures and hypercalcaemia
• U&E: Renal impairment 50% possibly due to the toxicity of light chains - BJP. Send Spot urine for Bence Jones protein (BJP); not quantitative but can be used for monitoring
• Consider 24hr urinary protein excretion with protein electrophoresis, immunofixation and quantification of BJP. If concerns regarding inaccurate collection, the Urine Protein/Creatinine ratio can be assessed
• Serum protein electrophoresis with immunofixation and paraprotein (PP)quantification: Monoclonal band - IgG (50%) IgA (25%), free monoclonal light chains (BJP) in 20% and the rest are IgM/D/E. Monoclonal Ig > 30 g/l
• Raised Beta-2 Microglobulin and LDH and are prognostic and match tumour mass
• Raised IL-1, IL-6, IL-11 and TNF-beta suggest a poor prognosis
• Alkaline phosphatase is classically normal and so is bone scan - do a skeletal survey
• Bone marrow aspirate & trephine: plasma cells. Myeloma cells express plasma cell antigens - PCA-1 and CD10 but also myelomonocytic CD33. FISH for t(4;14), t(14;16), del(17p) and 1p-/1q+ on purified plasma cells (PCs)oInformative flow cytometry markers are combined CD38, CD138 and CD45 for identification and CD19,CD56, CD27, CD81, CD117 for further characterization of BM PCs(optional); useful minimal residual disease (MRD)
• NT-proBNP and Troponin if suspected cardiac amyloid
• Radiology: Newly diagnosed myeloma patients, in order of preference: Whole-body MRI, whole-body CT. PET-CT is recommended for soft tissue plasmacytomas. MRI of the spine in suspected spinal cord compression
• ECG, Echo or MUGA if suspected cardiac amyloid. Cardiac MR and DPD scintigraphy if cardiac amyloid is suspected

CRAB Mnemonic

• Hypercalcaemia (corrected Ca²⁺>2.75mmol/L) : Myeloma breaks down bone and releases high calcium levels in the blood.
• Renal impairment (no other cause) CrCl <40, Cr>177damage to kidneys due to abnormally high levels of abnormal proteins in the blood which can damage tubules.
• Anaemia (Hb <100g/L or <20g below normal) not due to other causes Anaemia caused by myeloma
• Bone lesions (lytic lesions or osteoporosis): Bone pain affects a majority of myeloma patients, usually in the spine and ribs. Bone fractures and spinal cord compression is also common. The breakdown of bone also leads to the release of calcium in the blood, leading to hypercalcemia. It is common for bone problems to cause pain, breaks, and spinal problems.

Complications

• Pathologic fractures
• Hypercalcemia
• Renal failure
• Recurrent infection
• Anaemia
• Spinal cord compression (10% of all multiple myeloma [MM] patients)

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

Management

• Young and fit patients: Consider Velcade (Bortezomib a proteasome inhibitors. ) containing regimens. Often involves Thalidomide, Dexamethasone or Cyclophosphamide. Bortezomib is also given. High dose melphalan and autologous stem cell transplantation (ASCT)are considered standard of care in first and second (and occasionally third)remission if patients are deemed fit.
• Other regimens involving Velcade, Cyclophosphamide, Dexamethasone, Thalidomide, Lenalidomide
• Supportive - transfusions for anaemia
• IV Pamidronate and rehydration should be given to reduces bone pain and manage hypercalcaemia. It may improve survival.
• Vertebral Fractures - orthopaedic referral for possible kyphoplasty, which involves inflating a balloon in the affected vertebral body and filling this with methyl methacrylate cement in order to restore the vertebral shape.
• Manage pain - NSAIDs - watch renal function
• Hyperviscosity - plasma exchange
• May need Allopurinol for hyperuricaemia
• Prednisolone may also be used for the hypercalcaemia
• Radiotherapy may be useful to treat individual bone lesions
• Discussions with patient and family. Support.
• Supportive and symptomatic e.g. treat anaemia, infections due to immune paresis

References

• Guidelines for the management of Multiple Myeloma