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Haematology > Haem: Plasma cell myeloma and MGUS > Flashcards

Haem: Plasma cell myeloma and MGUS Flashcards

1
Q

What is the primary job of plasma cells?

A

To produce immunoglobulins and antibodies

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2
Q

What is myeloma essentially?

A

cancer of very mature B cells

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3
Q

How are plasma cells produced?

A

Centroblasts mature in the lymph nodes and are stimulated by antigens to turn into plasmablasts

Plasmablasts are then refined to perfectly fit the antigens they were exposed to

They downregulate and upregulate certain transcription factors

These plasmablasts eventually turn into plasma cells

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4
Q

What is MGUS?

A

Pre malignant condition. While only 1-2% of these annually progress onto myeloma, all myeloma definitely spring from MGUS.

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5
Q

What are the 2 most common haematopoietic malignancies?

A

B cell lymphomas

MGUS

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6
Q

What is the biochem of MGUS?

A

Monoclonal serum protein (IgG/ IgA) < 30g/L
Bone marrow plasma cells < 10%
Annual risk to progression of multiple myeloma is 1-2%
This is rare in young, increasing incidence with age (5% < 70 years)

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7
Q

What symptoms does MGUS have?

A

None

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8
Q

What is the biochem of smouldering myeloma?

A

Monoclonal serum protein (IgG/ IgA) ≥ 30g/L
Bone marrow plasma cells ≥ 10%
Annual risk of progression to multiple myeloma is 10%

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9
Q

What is the pnemonic for MGUS diagnosis?

A

CRAB

Calcium high
Renal impairment
Anaemia
Bone lesions

+ monoclonal protein

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10
Q

What kind of bone lesions do you find in myeloma?

A

Osteolytic

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11
Q

What are the 2 medical emergencies of myeloma?

A

Spinal cord compression

Hypercalcaemia

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12
Q

How to diagnose spinal cord compression?

A

MRI
Ig studies
FLC

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13
Q

What to do for spinal cord compression?

A

Dexamethasone

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14
Q

What criteria is used for MGUS?

A

Mayo

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15
Q

What is the most common cytogenetic abnormality in myeloma?

A

Hyper diploid karyotype

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16
Q

Name 2 events that happens in the tumour microenvironment?

A

Increased angiogenesis

Increased bone resorption

17
Q

How is myeloma diagnosed?

A

Ig studies - Serum electrophoresis, FLC ratio, 24 hour Bence Jones urine

Bone marrow aspirate and biopsy

FISH analysis

Flow cytometry immunophenotyping

18
Q

In the Bone marrow aspirate and biopsy what CD cells would you see?

A

CD138

Won’t see CD 19 or CD 20 as they are expressed by B cells

19
Q

Which cancers are always CD 20 positive?

A

Lymphoma and CLL

20
Q

What are the 5 ways of treating myeloma?

A 
Cytotoxic drugs - alkylating agents
Steroids 
Immunomodulators - Thalidomide 
Monoclonal antibodies - Daratumumab
Proteosome inhibitors - Bortezomib
21
Q

Name an alkylating agent

A

Melphalan

22
Q

How are stem cell transplants done?

A

Reduced myeloma burden by drugs

Harvest stem cells from bone marrow

Single high dose Melphalan to kill myeloma cells but this will also destroy the bone marrow

Then re infuse with stem cells that were harvested

23
Q

What are the 2 ways proteosome inhibitors kill myeloma cells?

A

Upstream effect; If the proteasome is BLOCKED, there will be accumulation of unrequired proteins. Many of these proteins will precipitate, BLOCKING cellular function.
Since myeloma cells secrete lots of immunoglobulin and paraprotein, they are susceptible to this assault on the recycling machinery and will result in myeloma cell death.

Downstream effect: If the proteasome is BLOCKED, there will be accumulation of proteins needing to be degraded. However, there will also be a shortage of amino acids/ peptides required to build new proteins. So, they CANNOT make new proteins.

24
Q

How do immunomodulatory drugs work?

A

enhanced degradation of transcription factors (IKZF1 + IKZF3) which are required for B cell development.

25
Q

What are the imaging tecnhiques used to investigate multiple myeloma?

A

MRI - Bone marrow infiltration
CT - small lytic lesions
PET - detects active disease

26
Q

How does myeloma cause kidney injury?

A

FLC activate inflammatory mediators in the proximal tubule epithelium

Proximal tubule necrosis

Fanconi syndrome (renal tubule acidosis with failure of reabsorption in the proximal tubule) with light chain crystal deposition

Cast nephropathy - FLC and Bence Jones proteinurea

27
Q

What is the biochem for kidney injury due to myeloma?

A

Serum creatinine > 177

eGFR < 40

28
Q

What are the most common infections due to myeloma and why is it caused?

A

Viral - Herpes zoster re activation

Due to low Ig levels

29
Q

What happens in myeloma and AL amyloidosis?

A

Misfolded FLC turn into amyloid and deposit on organs

Stain well with Congo red

Lamda light chain involved

30
Q

What are the symptoms of AL amyloidosis with myeloma?

A

Nephrotic syndrome

Unexplained HF - Check serum FLC, High BNP, Abnormal ECG

Abnormal LFTs

Macroglossia

ED

31
Q

What is MGRS?

A

B cell clonal lymphoproliferation where:

  • > 1 kidney lesions due to Ig
  • B cell clone does not cause tumour complications

Haematology (10 decks)

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