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Multiple Myeloma Flashcards

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1
Q

what group of patients does multiple myeloma commonly affect?

A

> 60s (peak 70s)
males>females
black Africans

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2
Q

what are the genes associated with multiple myeloma?

A

HLA Cw5

Also ATM, BRAF, CCND1, DIS3, FAM46C, KRAS, NRAS and TP53

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3
Q

what chromosomal factors are associated with myeloma?

A

chromosome 13, hyperdiploidy, and p53 deletions

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4
Q

what environmental factors are associated with myeloma?

A

agricultural, food and petrochemical industries, and long-term exposure to hair dyes

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5
Q

what other factors are associated with myeloma?

A

Monoclonal gammopathy of unknown significance
Radiation
EBV

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6
Q

myeloma is proliferation of which type of cell?

A

plasma cells

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7
Q

what are plasma cells?

A

mature B cells that secrete certain antibodies on its surface

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8
Q

proliferation of plasma cells leads to…

A

formation of abundant one type of immunoglobulin

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9
Q

what subtypes of immunoglobulins are common in myeloma?

A

IgGk

then IgA and pure light chain myeloma (k or lambda)

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10
Q

what is the impact of myeloma on bone marrow?

A

plasma cells are increased in bone marrow
pushes other immune cells out
= immunodeficiency

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11
Q

what is multiple myeloma

A

raised plasma cells in the blood and bone marrow

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12
Q

what is the impact of multiple myeloma on B and T cells?

A

B cell dysfunction – decreased humoral immunity – susceptible to bacteria
T cell function normal – viral protection
(as B cells mature in bone marrow, T cells in lymph nodes)
dysregulation of cyclin D

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13
Q

what is the mechanism of myeloma on bones?

A

Osteoclast stimulation
Osteoblast
inhibition

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14
Q

what is the consequence of myeloma on bones?

A

bone destruction

hypercalcaemia

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15
Q

what will ALP and bone scans show in bones of those with myeloma?

A 
ALP normal (not high) – no stimulation of osteoblasts 
Nuclear bone scan not affective – no stimulation of osteoblasts = lytic
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16
Q

how are osteoclasts stimulated in multiple myeloma?

A

Bone marrow fibroblasts & macrophages produce IL-6
Myeloma cells produce IL-6
IL-6 activates RANK-ligand causing stimulation of osteoclasts

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17
Q

how are osteoblasts inhibited in multiple myeloma?

A

Myeloma cells secrete an inhibitor of osteoblast differentiation

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18
Q

what are the different ways kidneys are affected by myeloma?

A 
chronic renal failure
kidney stones
bence hones renal disease 
metastases
primary amyloidosis 
pyelonephritis
proteinuria
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19
Q

how does chronic renal failure occur in multiple myeloma?

A

raised calcium, amyloid deposition, BJ proteins causing tubular obstruction, direct toxicity of paraproteins to tubules, use of NSAIDs for pain

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20
Q

how do kidney stones occur in multiple myeloma?

A

increased calcium

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21
Q

what is bence jones renal disease

A

Proteinaceous tubular casts impact on renal function (BJ, immunoglobulins, Tamm-Horsfall protein)

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22
Q

what is primary amyloidosis and how does it affect renal function in multiple myeloma?

Study These Flashcards
A

AL fibrillar protein derived from immunoglobulin light chain, light chains are converted into amyloid light chain deposition in glomeruli or interstitium

23
Q

why does pyelonephritis occur in multiple myeloma?

Study These Flashcards
A

B lymphocyte dysfunction, dehydration

24
Q

how does proteinuria occur in multiple myeloma?

Study These Flashcards
A

BJ jones abundance exceeds kidneys ability to absorb protein

25
what is the disease progression of myeloma?
Monoclonal gammopathy of undetermined significance → smoldering multiple myeloma → multiple myeloma → plasma cell leukaemia
26
what are bence jones proteins?
light chains that end up in urine
27
what are the clinical features of bone disease in myeloma?
Pain (vertebrae, ribs, skull, sternum) Punched out lytic bone lesions Pathological fractures Hypercalcaemia
28
what are the haematological features of myeloma?
Normocytic normochromic anaemia Raised ESR Increased bleeding time
29
what are the different neuropathies that occur in myeloma?
radiculopathy | neuropathy
30
how does radiculopathy occur in myeloma?
vertebrae fractures/compressions impinge nerve route
31
how does neuropathy occur n myeloma?
amyloid deposition infiltrates soft tissue around median nerve – carpal tunnel syndrome
32
what are the clinical features of hypercalcaemia in myeloma?
lethargy, confusion, weakness
33
what will the renal function be in those with myeloma?
reduced
34
what are the organisms commonly causing infection in myeloma?
S.aureus, strep pneumoniae, Klebsiella Ecoli, H influenza
35
what are plasmacytomas?
tumours associated with myeloma, tumours made of plasma cells
36
what are the symptoms of hyper viscosity syndrome?
Spontaneous gum bleeding, epistaxis, rectal bleeding, vertigo, hearing loss, paraesthesia’s, visual changes, headaches/seizures/somnolence, HF, SOB, hypoxia, fatigue
37
what is the general criteria of multiple myeloma?
Monoclonal protein band in serum or urine electrophoresis Plasma cells ↑ on marrow biopsy Evidence of end-organ damage from myeloma: Hypercalcemia, Renal insufficiency, Anaemia Bone lesions: a skeletal survey after diagnosis detects bone disease: x-rays of the chest, all of spine; skull; pelvis +/- Tc99m MIBI and PET
38
what combination of major/minor criteria is required?
1 major + 1 minor, or 3 minor
39
what are the major criteria for multiple myeloma?
Plasmacytoma (as demonstrated on evaluation of biopsy specimen) 30% plasma cells in a bone marrow sample Elevated levels of M protein in the blood or urine
40
what are the minor criteria for multiple myeloma?
10% to 30% plasma cells in a bone marrow sample. Minor elevations in the level of M protein in the blood or urine. Osteolytic lesions (as demonstrated on imaging studies). Low levels of antibodies (not produced by the cancer cells) in the blood.
41
what is the criteria of smouldering myeloma?
o Serum paraprotein >30 g/l or urinary monoclonal protein ≥500 mg per 24 h AND/OR o Clonal plasma cells >10% and <60% on bone marrow biopsy AND o No evidence of end organ damage attributed to plasma cell disorder AND o No myeloma-defining event (>60% plasma cells in bone marrow OR Involved/Uninvolved light chain ratio>100)
42
what is the criteria for MGUS?
o A monoclonal paraprotein band less than 30 g/l (< 3g/dl); o Plasma cells less than 10% on bone marrow examination; o No evidence of bone lesions, anemia, hypercalcemia, or chronic kidney disease related to the paraprotein, and o No evidence of another B-cell proliferative disorder.
43
what is the criteria for stage 1 myeloma?
 >35g/L albumin |  <3.5mg/L a2-microglobulin
44
what is the criteria for stage 2 myeloma?
do not fit the criteria for the other two stages
45
what is the criteria for stage 3 myeloma?
 <35g/dL albumin |  >5.5mg/L a2-microglobulinaemia
46
what is the management of multiple myeloma?
``` VAD Stem cell transplant Combination therapy Supportive Bisphosphonates ```
47
what are the complications of myeloma?
• Renal impairment Hypercalcaemia Spinal cord compression Hypersensitivity
48
what are the complications of myeloma?
Renal impairment Hypercalcaemia Spinal cord compression Hypersensitivity
49
What is VAD chemotherapy used in myeloma?
vincristine, Adriamycin, dexamethasone,
50
what is the process of a stem cell transplant?
Induction therapy Transplant - combination of steroids, cytotoxic chemotherapy (cyclophosphamide), immunomodulating agent (thalidomide or lenalidomide) Lenalidomide/thalidomide 12 months post transplant
51
what is the supportive therapy used in myeloma?
Anaemia correction – blood transfusion and/or EPO Flu vaccine and antibiotics Pain management (beware NSAID long-term) Orthopaedic surgery for fractures
52
what is the diagnostic investigations of myeloma?
detection of the light chain via serum electrophoresis + immunofixation+ FLC” Electrophoresis o Will show intact immunoglobulins o Fragments of heavy or light chains o These proteins are called paraprotein = M protein Immunofixations – type of paraprotein Serum FLC – increase sensitivity of the serum electrophoresis
53
what is the main diagnostic test for NHS in myeloma?
Bone marrow sample - shows plasma cell infiltration
54
What other investigations can be used for myeloma? (16)
* FBC – Hb, WCC and platelet count will be normal or low * ESR – almost always high * CRP – almost always raised * Blood film – there may be rouleaux formation due to increased paraproteins * U+E – may be evidence of renal failure – in which cases both may be high, resulting in a reduced eGFR * Serum lactate dehydrogenase and serum β2-microglobulin – useful in predicting prognosis * Serum calcium – normal or raised * ALP – usually normal * Total protein – normal or raised * Serum albumin – normal or low * Serum paraprotein * Uric acid – normal or raised * Skeletal survey –may show characteristic lytic lesions – most commonly in the skull * Urine protein electrophoresis – identifies presence of Bence-Jones proteins * 24-hour urine immunofixation –this is useful for checking the subtype of light chains * Bence-Jones proteins

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