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Haematology > Myeloma and Other Plasma Cell Disorders > Flashcards

Myeloma and Other Plasma Cell Disorders Flashcards

1
Q

where are B cells derived from?

A

derived from pluripotent haematopoietic stem cells in bone marrow

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2
Q

role of B cells?

A

part of adaptive immune system
dual role
- antibody production
- acting as antigen presenting cells

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3
Q

what are immunoglobulins?

A

antibodies produced by B cells and by plasma cells
proteins made of 2 heavy chains (long) and 2 light chains (short)
each antibody recognizes a specific antigen

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4
Q

where are the antigen binding sites on antibody?

A

tip variable region of Fab portion

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5
Q

structure of different types of antibody?

A

IgM = pentamer
IgA = dimer
IgG, IgD, IgE = monomer

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6
Q

describe process of B cell development in bone marrow?

A

under control/influence of microenvironment
variable region of Ig generated from V-D-J region recombination early in development
self reactive cells are removed
immature B cells with Ig on their surface exit bone marrow ready to meet their target

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7
Q

describe normal B lymphocyte maturation

A

stem cells > lymphoid precursors > pro B cells > pre B cells > IgM B cells > IgG, IgE, IgA, IgM plasma cells

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8
Q

function of B cells in the periphery?

A

travel to the follicle germinal centre of the lymph node
identify the antigen and improve the fit by somatic mutation or be deleted
may return to the marrow as plasma cell or circulate as memory B cell

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9
Q

what are plasma cells?

A

type of B cell

factory cell which pumps out antibody

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10
Q

what do plasma cells look like?

A

has characteristic “clock face” nucleus
open chromatin (synthesising mRNA)
plentiful blue cytoplasm laden with protein
pale perinuclear area with Golgi apparatus

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11
Q

describe polyclonal increase in Ig?

A

polyclonal increase

produced by many different plasma cell clones

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12
Q

immunoglobulins increase in polyclonal way in response to what?

A

infection
autoimmune
malignancy (reaction of host to the malignant clone)
liver disease

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13
Q

describe monoclonal increase in Ig?

A

all derived from clonal expansion of a single B cell

all have identical antibody structure and specificity (size and charge)

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14
Q

monoclonal Ig are known as what?

A

paraprotein

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15
Q

monoclonal rise in Ig is a marker of what?

A

underlying clonal B cell disorder

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16
Q

how are immunoglobulins detected?

A

serum electrophoresis
- the separated serum proteins appear as distinct bands or zones (proteins move at different rates depending on their size and charge)
can detect abnormal protein bands

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17
Q

what is serum immunofixation?

A

to classify the abnormal protein band

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18
Q

what is bence jones protein?

A

excess free Ig light chains detected in urine electrophoresis
some excess always produced but more excess can indicate polyclonal increase in number of plasma cells due to infection or monoclonal increase such as multiple myeloma

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19
Q

normal amount of free light chain production per day?

A

0.5g per day

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20
Q

components of free light chains (bence jones protein)?

A

kappa free light chain (monomer)

lambda = dimer)

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21
Q

myeloma accounts for how many cases of paraproteinaemia?

A

18%

22
Q

what is a myeloma?

A

plasma cell malignancy

23
Q

progression from normal plasma cell to myeloma?

A

several genetic hits cause progression from normal plasma cell > MGUS clone (pre-malignant) > asymptomatic myeloma (malignant but no organ damage) > myeloma

24
Q

how can myeloma affect the body?

A

direct tumour cell effects

paraprotein mediated effects

25
Q

direct tumour cell effects?

A

bone lesions
increased calcium
bone pain
replace normal bone marrow causing marrow failure

26
Q

paraprotein mediated effects of myeloma?

A

renal failure
immune suppression
hyperviscosity
amyloid

27
Q

how is myeloma classified?

A 
by type of antibody produced
IgG (59%)
IgA (21%)
bence jones (15%)
others around 1%
28
Q

characteristic feature of lytic bone disease on imaging?

A

punched out lytic lesions

can have wedge compression fracture in thoracic vertebra

29
Q

how does lytic bone disease occur in myeloma?

A

myeloma cells proliferate > IL-6 produced which activates osteoclasts

30
Q

features of hypercalcaemia?

A 
stones
bones
abdominal groans
psychiatric moans
thirst
dehydration
renal impairment
31
Q

how does myeloma affect the kidney?

A 
30% have renal impairment at diagnosis
tubular cell damage by free light chains
light chain deposition
sepsis
hypercalcaemia and dehydration
drugs (NSAIDs)
hyperuricaemia
amyloid
32
Q

how does myeloma cause kidney damage?

A

free light chains are small enough to filter through glomerular pores
kidneys function to prevent loss of small proteins like light chains so proximal tubules reabsorb these
proximal tubules can be overwhelmed or damaged then light chains pass into loops of henle producing tamm Horsfall protein which can combine with light chains to form insoluble casts which block the nephron

33
Q

management of cast nephropathy (renal damage due to myeloma)?

A

can be reversible with prompt treatment
hydration
stop nephrotoxic drugs
switch off light chain production with steroids/chemo

34
Q

management of myeloma?

A

combination chemo = mainstay
combination with
- corticosteroids
- alkylating agents (cyclophosphamide, melphalan)
- novel agents (thalidomide, bortezomib)
- can do high dose chemo/autologous stem cell transplant in fit patients

35
Q

what is autologous stem cell transplant?

A

way of delivering very high dose chemo relatively safely
give drugs to release blood stem cells from marrow > collect stem cells > freeze stem cells until needed > give chemo to remove immune system > return thawed stem cells > give supportive treatment for 4 weeks

36
Q

monoclonal antibody treatment for myeloma?

A

daratumumab?

37
Q

effectiveness of myeloma treatment?

A

relapse is inevitable

5-10 year survival in young people

38
Q

symptoms control in myeloma?

A 
opiate analgesia (avoid NSAIDs)
local radiotherapy (pain relief or spinal cord compression)
bisphosphonates (hypercalcaemia and bone pain)
vertebroplasty (inject sterile cement into fractured bone to stabilise)
39
Q

what is MGUS?

A

monoclonal gammopathy of undetermined significance

40
Q

features of MGUS?

A 
paraprotein <30g/L
bone marrow plasma cells <10%
no evidence of myeloma end organ damage
- normal calcium
- normal renal function
- normal Hb
- no lytic lesions
- no increase in infections
41
Q

how is MGUS most common in?

A

increase with age of elderly

42
Q

what is AL amyloidosis?

A

rare disorder
small plasma cells clone
due to mutation in the light chain > altered structure
results in precipitation of light chain in the tissues as an insoluble beta pleated sheet
often presents late with organ damage

43
Q

presenting features of AL amyloidosis?

A 
organ damage
slowly progressive
multisystem disease
different protein to SAA amyloidosis (chronic amyloidosis) and familial amyloidosis
poor prognosis (esp if cardiac amyloid)
44
Q

AL amyloidosis treatment?

A

chemo

similar to myeloma to switch off light chain supply

45
Q

what organ damage can occur in AL amyloid?

A 
kidney
heart
liver
neuropathy (autonomic/peripheral)
GI tract (malabsorption)
46
Q

how is amyloidosis diagnosed and staged?

A

organ biopsy confirming AL amyloid deposition
- congo red stain
- (rectal/fat biopsy if high clinical suspicion)
evidence of deposition in other organs (SAP scan, ECHO, nephrotic range proteinuria)

47
Q

what is SAP scan?

A

indium labelled serum amyloid scintography used to monitor disease burden and response
localises rapidly and specifically to amyloid deposits in proportion to quantity of amyloid present

48
Q

how deos AL amyloid stain?

A

congo red

apple green birefringence under polarised light

49
Q

what is waldenstrom’s macroglobulinaemia?

A

IgM paraprotein due to lymphoplasmacytoid neoplasm
clonal disorder of cells intermediate between lymphocyte and a plasma cell
has characteristic IgM paraprotein

50
Q

tumour effects of waldenstroms macroglobulinaemia?

A

lymphadenopathy
splenomegaly
marrow failure

51
Q

paraprotein effects of macroglobulinaemia?

A

hyperviscosity

neuropathy

Haematology (26 decks)

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