sc2 2014 multiple myeloma (1)
DESCRIPTION
very helpfulTRANSCRIPT
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Multiple myeloma
Department of Medicine
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DEFINITION
Multiple Myeloma = neoplastic proliferation of a single clone of plasma cells producing a
monoclonal immunoglobulin
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EPIDEMIOLOGY
• 10% of all haematological cancers• Annual Incidence = 5 per 100,000• Male > female• Afro-Caribbeans > Caucasians• Median age: 66 years
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RISK FACTORS
• Cause: Unknown• Postulated - Environmental trigger in a Genetically susceptible individual
• Risk Factors– Ionizing radiation – Occupational exposure(benzene)– Age: Peak incidence in 7th decade of life– 1st Degree Relative with Myeloma
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SYMPTOMS
• Bone Pain– Back and ribs– sudden and severe– induced by movement– does not occur at night except with change of
position
• Pathological fractures• Weight-loss• Fatigue• Recurrent infections• Fever
Symptoms of hyperviscosity• Bleeding • Headache • blurred vision
Hypercalcaemia• Vomiting• Constipation• Abdominal Pain• Polydipsia• Polyuria• Confusion• Depression
Spinal Cord Compression• Severe back pain• Bladder dysfunction• Bowel Dysfunction• Erectile dysfunction
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SIGNS
• Fever• Weight-loss• Anaemia
– Palmar Pallor– Conjunctival Pallor
• Carpal tunnel syndrome• Peripheral neuropathies• Lymphadenopathy• Hepatomegaly• Splenomegaly• Tenderness on palpation of bones,
especially long bones
Spinal cord compression• Lower limb weakness• Lower limb paraesthesia• Perianal apraesthesia• Reduced anal tone (PR exam)• Upgoing plantars
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DIFFERENTIAL DIAGNOSIS
• Asymptomatic Multiple Myeloma / Smoldering Multiple Myeloma (SMM)– Serum monoclonal protein ≥3 g/dL and/or ≥10 to <60 percent bone marrow clonal plasma cells– Absence of lytic lesions, anemia, hypercalcemia, and renal insufficiency (end-organ damage) that can be
attributed to the plasma cell proliferative disorder
• Monoclonal Gammopathy of Undetermined Significance (MGUS)– Serum monoclonal protein (whether IgA, IgG, or IgM) <3 g/dL– Clonal bone marrow plasma cells <10 percent– Absence of lytic lesions, anemia, hypercalcemia, and renal insufficiency (end-organ damage) that can be
attributed to the plasma cell proliferative disorder
• Waldenström Macroglobulinemia (WM)• Solitary Plasmacytoma• Primary Amyloidosis (AL)• POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin
changes) syndrome• Metastatic Carcinoma
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Investigations
Bloods• FBC
– normocytic, normochromic anemia
• U&E– Elevated creatinine
• CPMA– Hypercalcemia
• LFT– Normal Alkaline phosphatase
• ESR– Elevated ESR
• Blood film– Rouleaux formation
• Urine dipstick– negative for protein (albumin)
(Unable to detect urinary monoclonal Bence-Jones proteinuria)
Screening test• Serum Protein Electrophoresis (SPEP)• Urine Electrophoresis (UPEP)
• β2-microglobulin
• Bone marrow aspirate– >10% plasma cells in the bone marrow
or– histologically proven plasma cell infiltration
• Skeletal survey– lytic bone lesion
• MRI Spine (URGENT if Cord Compression)– Spinal Cord Compression (extramedullary
plasmacytoma)
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Investigation
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Investigations
Bone Marrow Aspiration
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Investigations
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Investigation
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CRAB Acronym:‒ Increased Calcium‒ Renal insufficiency‒ Anemia‒ lytic Bone lesions
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TreatmentMultiple Myeloma• Chemotherapy• Hematopoietic cell transplantation
Hypercalcaemia• IV Normal Saline• Corticosteroids• Bisphosphonates
– Zoledronic acid– Pamidronate
• Allopurinol (Tumor lysis)• Erythropoetin (anaemia)• Blood component replacements
– RCC– Platelets
Renal Impairment• Avoid nephrotoxic Medications
– NSAID’s
– ACE I / ARB / Direct Renin Inhibitors
– Aminoglycosides
• IV Hydration• Plasmapheresis• Hemodialysis
Infections• vaccines• Antibiotics• Anti-virals• IV immunoglobulin
Spinal Cord Compression• Dexamethasone• Radiation therapy• Surgical decompression
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COMPLICATIONS
• Pathological Fractures• Cord Compression• Carpal tunnel Syndrome• Polyneuropathies• Anaemia• Infections• Renal Failure• Hypercalcaemia• Nephrocalcinosis• Amyloidosis• Hyperviscosity
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PROGNOSIS
• The 5-year relative survival rate 35%
• Prognosis worse with • High tumour burden • Fast proliferation rate• Older age• Beta 2 microglobulin• Hypercalcaemia• Bence Jones proteinemia• Renal impairment
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REFERENCES
• Smith et al. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol. 2006;132(4):410.
• UpToDate• Oxford handbook of clinical medicine 8th Edition
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SAMPLE MCQ
A 78 year old woman presents to her General Practitioner with 2 month history of severe back pain worse with movement. She denies any history of trauma. She also has weight loss 4 kg over 2 months and fatigue. On examination she has palmar and conjunctival pallor, hepatomegaly and splenomegaly and is tender on palpitation of her back. Which of the follow is the most likely symptom indicative of need for an urgent MRI Spine
a)Back pain
b)Bowel dysfunction
c)Down-going plantars
d)Perianal paraesthesia
e)Reduced lower limb power
Answer = b
AA 78 year old woman presents to her General Practitioner with 2 month history of severe back pain worse with movement. She denies any history of trauma. She also has weight loss 4 kg over 2 months and fatigue. On examination she has palmar and conjunctival pallor, hepatomegaly and splenomegaly and is tender on palpitation of her back. A diagnosis of multiple myeloma is suspected. What is the most useful test to perform?
a)Bone Profile (Calcium / Phosphate / Magnesium / Albumin)
b)ESR
c)Peripheral Blood Film
d)Urine Protein Dipstick
e)Urine Protein Electrophoresis
Answer = e
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SAMPLE MCQ
A 78 year old woman presents to her General Practitioner with 2 month history of severe back pain worse with movement. She denies any history of trauma. She also has weight loss 4 kg over 2 months and fatigue. On examination she has palmar and conjunctival pallor, hepatomegaly and splenomegaly and is tender on palpitation of her back. The GP orders a test to detect Bence-Jones proteins. Which of the follow test did the GP order?
a)Bone marrow aspirate
b)Peripheral Blood Film
c)Serum Protein Electrophoresis
d)Urine Protein Dipstick
e)Urine Protein Electrophoresis
Answer = e
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SAMPLE MeQ
A 78 year old woman presents to her General Practitioner with 2 month history of severe back pain worse with movement. She denies any history of trauma. She also has weight loss 4 kg over 2 months and fatigue. On examination she has palmar and conjunctival pallor, hepatomegaly and splenomegaly and is tender on palpitation of her back.
a)List differential diagnoses for this presentation other than multiple myeloma. ( 6 marks)
See Slide 7
b)List 3 tests used to establish the diagnosis (6 marks)
Serum Protein Electrophoresis (SPEP)
Urine Electrophoresis (UPEP)
β2-microglobulin
Bone marrow aspirate
c)She presents with increasing confusion over next 2 days. What electrolyte should be checked? ( 2 marks)
Calcium
d)Mention 2 treatments to treat confuion caused by electrolyte abnormality ( 6 marks)
IV Hydration
Steroids
Bisphosphonate