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Haematology > Multiple Myeloma > Flashcards

Multiple Myeloma Flashcards

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?

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?

A

B lymphocyte dysfunction, dehydration

24
Q

how does proteinuria occur in multiple myeloma?

A

BJ jones abundance exceeds kidneys ability to absorb protein

25
Q

what is the disease progression of myeloma?

A

Monoclonal gammopathy of undetermined significance → smoldering multiple myeloma → multiple myeloma → plasma cell leukaemia

26
Q

what are bence jones proteins?

A

light chains that end up in urine

27
Q

what are the clinical features of bone disease in myeloma?

A

Pain (vertebrae, ribs, skull, sternum)
Punched out lytic bone lesions
Pathological fractures
Hypercalcaemia

28
Q

what are the haematological features of myeloma?

A

Normocytic normochromic anaemia
Raised ESR
Increased bleeding time

29
Q

what are the different neuropathies that occur in myeloma?

A

radiculopathy

neuropathy

30
Q

how does radiculopathy occur in myeloma?

A

vertebrae fractures/compressions impinge nerve route

31
Q

how does neuropathy occur n myeloma?

A

amyloid deposition infiltrates soft tissue around median nerve – carpal tunnel syndrome

32
Q

what are the clinical features of hypercalcaemia in myeloma?

A

lethargy, confusion, weakness

33
Q

what will the renal function be in those with myeloma?

A

reduced

34
Q

what are the organisms commonly causing infection in myeloma?

A

S.aureus, strep pneumoniae, Klebsiella Ecoli, H influenza

35
Q

what are plasmacytomas?

A

tumours associated with myeloma, tumours made of plasma cells

36
Q

what are the symptoms of hyper viscosity syndrome?

A

Spontaneous gum bleeding, epistaxis, rectal bleeding, vertigo, hearing loss, paraesthesia’s, visual changes, headaches/seizures/somnolence, HF, SOB, hypoxia, fatigue

37
Q

what is the general criteria of multiple myeloma?

A

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
Q

what combination of major/minor criteria is required?

A

1 major + 1 minor, or 3 minor

39
Q

what are the major criteria for multiple myeloma?

A

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
Q

what are the minor criteria for multiple myeloma?

A

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
Q

what is the criteria of smouldering myeloma?

A

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
Q

what is the criteria for MGUS?

A

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
Q

what is the criteria for stage 1 myeloma?

A

 >35g/L albumin

 <3.5mg/L a2-microglobulin

44
Q

what is the criteria for stage 2 myeloma?

A

do not fit the criteria for the other two stages

45
Q

what is the criteria for stage 3 myeloma?

A

 <35g/dL albumin

 >5.5mg/L a2-microglobulinaemia

46
Q

what is the management of multiple myeloma?

A 
VAD
Stem cell transplant
Combination therapy
Supportive
Bisphosphonates
47
Q

what are the complications of myeloma?

A

• Renal impairment
Hypercalcaemia
Spinal cord compression Hypersensitivity

48
Q

what are the complications of myeloma?

A

Renal impairment
Hypercalcaemia
Spinal cord compression Hypersensitivity

49
Q

What is VAD chemotherapy used in myeloma?

A

vincristine, Adriamycin, dexamethasone,

50
Q

what is the process of a stem cell transplant?

A

Induction therapy
Transplant - combination of steroids, cytotoxic chemotherapy (cyclophosphamide), immunomodulating agent (thalidomide or lenalidomide)
Lenalidomide/thalidomide 12 months post transplant

51
Q

what is the supportive therapy used in myeloma?

A

Anaemia correction – blood transfusion and/or EPO
Flu vaccine and antibiotics
Pain management (beware NSAID long-term)
Orthopaedic surgery for fractures

52
Q

what is the diagnostic investigations of myeloma?

A

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
Q

what is the main diagnostic test for NHS in myeloma?

A

Bone marrow sample - shows plasma cell infiltration

54
Q

What other investigations can be used for myeloma? (16)

A
  • 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

Haematology (13 decks)

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