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Haematology > Haematology 11 - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance > Flashcards

Haematology 11 - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance Flashcards

1
Q

What immunoglobin is produced by myeloma cells?

A

One single type (eith IgG or IgA) which is known as paraprotein or M spike

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2
Q

What are Bence Jones proteins?

A

Urine monoclonal free light chains

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3
Q

What is Waldenstrom’s-Lymphoplacytic lymphoma?

A

A lymphoplasmocytic lymphoma with IgM paraprotein that causes visual disturbances

and mucous lesions???

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4
Q

What is the name of the premalignant condition that ALWAYS precedes myeloma?

A

Monoclonal gammaopathy of uncertain significance (MGUS)

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5
Q

What is the difference between a pre-myeloma MGUS and pre-lymphoma MGUS?

A

Pre-myeloma: IgG/A-producing B cells
Pre-lymphoma: IgM-producing B cells

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6
Q

What are the two most significant risk factors for myeloma?

A

Obesity
Black > causasians/ asians

age is another risk factor

  • chronic infection/ inflammation can increase the risk e.g. rheumatoid arthritis, viral (HHV8/HIV): immune system is more active whereby there is more active proliferation and differentiation of B cells, creating more of a chance for error.
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7
Q

What are the diagnostic criteria for MGUS?

A

Serum M-protein (i.e. paraprotein) <30g/L
BM clonal plasma cells <10%
Asymptomatic: no lytic lesions, no organ/tissue impairment, no clincal manifestation

no evidence of other B cell proliferation

**less severe version of multiple myeloma

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8
Q

What are the risk factor for progession of MGUS into multiple myeloma?

A
  1. non-IgG paraprotein (i.e. IgG is GOOD, G for Good!!)
  2. M spike (IgG/IgA paraprotein) >15
  3. abnromal serum free light chain ratio

average risk of progression to Multiple myeloma is 1%, so most people will not go on to develop multiple myeloma

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9
Q

What is smouldering myeloma?

A

Serum M-protein >30g/L
BM clonal plasma cells >10%
Asymptomatic- no signs of end organ damage

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10
Q

What is the clinical spectrum of multiple myeloma diseases?

A

Essentially MGUS is the least severe version

Then you have smouldering myeloma which is a more severe version but doesn’t have any organ damage

Then you have multiple myeloma

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11
Q

Diagnostic criteria of multiple myeloma

A

remember the values!!!

calcium: >2.75
creatinine: >177
anaemia: <100

**if it doesn’t meet the above criteria then you have smouldering myeloma**

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12
Q

Epidemiology of multiple myeloma

Risk factors for multiple myeloma

A
  • 2nd most common haemato;ogical malignancy
  • mostly affects older people- median age is 67 years old
  • men>women
  • black>caucasians and asians

___

RF: obesity

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13
Q

What % of plasma cells is there in symptomatic multiple myeloma?

A

>10%

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14
Q

What are the clinical effects of myeloma due to?

A
  1. BM microenvironment interaction
  2. Circulating paraprotein
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15
Q

What is the most notable interaction of myeloma cells with the bone marrow micro-environment?

A

Produce RANK ligand which stimulates osteoclasts to cause bone resorption

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16
Q

What is the incidence of IgM myeloma?

A

Very rare (<1% of myelomas)

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17
Q

What does CRAB stand for in myeloma diagnosis?

A

Calcium (hypercalcaemia, >2.75)

  • this is because of stimulation of osteoclasts which release calcium from the bone

Renal (creatinine >177/ eGFR <40)

Anaemia

  • this is because of infiltration of plasma cells into the bone marrow

Bone disease (see lytic lesions)

  • bone pain caused by infiltration of bone by plasma cells
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18
Q

What is the most common and 2nd most common cytogenetic abnormality in myeloma?

A
  1. Hyperdiploid karyotype: with extra copies of chromosome
  2. IgH gene rearrangement: chromosomal translocation of chromosome 14q32- locus for IgH gene

note these also occur in MGUS and smouldering myeloma. further secondary events causes progression into multiple myeloma e.g. (but not limited to):

  • Commonly mutations of NRAS and KRAS
  • Other translocations e.g. of Myc
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19
Q

What are the 3 2014 Myeloma Defining Events

A

BM plasma cells >60%
involved:uninvolved FLC ratio >100
>1 focal lesion on MRI

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20
Q

Which part of the skeleton is affected by myeloma?

A

Proximal skeleton (spine, ribs, pelvis, femur, skull, knees)

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21
Q

Where are myeloma patients most likely to feel pain?

A

Back, chest wall, pelvis

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22
Q

What % of myeloma patients present with bone disease?

A

80%

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23
Q

What scan is necessary to detect bone lesions in myeloma?

A

Whole body CT is first line (X ray is obsolete for this use)

PET scan can also be used - (often used in combination with CT/MRI)

Gold-standard = whole body diffusion-weighted MRI as this shows active vs treated disease

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24
Q

What are the 3 most likely emergency presentations of myeloma?

A

Cord compression- due to soft tissue mass or pathological fracture of vertebrae

Hypercalcaemia

renal failure

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25
What tests should be done to diagnose myeloma?
First: Serum protein electrophoreis- very sensitive screening monitoring: 24 hour bence jones protein Serum free light chains Next: Bone marrow aspirate- demonstrate infiltration by malignant plasma cells biopsy for immunohistochemistry: **CD138** FISH (for prognostic) Flow cytometry immunophenotyping: important **after treatment** to **detect small amounts of residual disease** if present
26
What is the best way to treat cord compression in myeloma?
Dexamethosone Radiotherapy
27
What type of nephropathy does myeloma cause?
Cast nephropathy
28
What causes kidney disease in multiple myeloma?
unable to filter overproduced serum free light chains = accumulation as casts = inflammation and fibrosis of proximal tubule They cause **_proximal tubule injur_**y and myeloma cast nephropathy
29
How should myeloma kidney disease be treated in an emergency?
hydration Bortezomib-based therapy is the cornerstone of myeloma kidney disease treatment - once the patients can become independent from dialysis their outcomes improve dramatically
30
How does myeloma affect immunity?
Serum levels of normal Igs reduced: **_immunoparesis-_** low normal serum immunoglobulins BM micro-environment interference also impairs myeloid, T and NK cells Chemo also impairs immune response myeloma immune evasion \*\*basically increased predisposition to infections
31
What is tested for in BM biopsy in suspected myeloma?
Immunohistochemistry for **_CD138_** - specific for myeloma cells in BM
32
What test can detect cytogenetic abnormalities of prognostic significance in myeloma?
FISH
33
What are the 3 parameters in the international staging system for myeloma?
Serum beta2 microglobulin Cytogenetic risk LDH
34
How does AL amyloidosis link to myeloma?
Misfolded FLCs aggregate into amyloid fibrils in target organs Amyloidosis can occur in background of MGUS/myeloma
35
How does amyloidosis affect the kidney?
Nephrotic syndrome i.e. NOT CAST NEPHROPATHY
36
Give 5 features of the clinical presentation of AL amyloidodis and common target organs
common target organs: kidney, heart(myocardium), liver, neuropathy Nephrotic syndrome * proteinuria (not bence jones protein), oedema Unexplained heart failure: determinant of prognosis: * cardiac amyloidossis has very poor prognosis Sensory neuropathy Abnormal liver function tests Macroglossia erectile dysfunction
37
What is MGRS?
Monoclonal gammaopathy of Renal significance
38
How is MGRS defined?
1. One or more kidney lesions caused by mechanisms related to the produced monoclonal immunoglobulin (Ig) 2. The underlying B cell clone does not cause tumor complications or meet current hematological criteria for immediate specific therapy Work up is similar to myeloma and most patinets will require myeloma type treatment
39
Recall 6 options for myeloma therapy
1. Alkylators (eg cyclophosphamide + Melphalan) 2. Steroids (eg dex + pred) 3. immunemodulators: Thalidomide, Lenalidomide 4. Cereblon-binding drugs 5. Proteosome inhibitors- Bortezomib + Carfilzomib 6. **Anti-CD38** (daratumumab)- monoclonal AB
40
Which monoclonal antibody is used in myeloma treatment?
Anti-CD38 (daratumumab)
41
What are the first investigations to be done in suspected myeloma?
Serum protein electrophoresis - this is for IgG/IgA Serum free light chains- this is for the light chains
42
4 main complications of multiple myeloma
* **Osteolytic bone lesions: fracture risk** * **​spinal chord compression** * **Anaemia** * **Kidney failure** * **recurrent Infections**
43
prognosis of myeloma
INCURABLE disease
44
comorbidities associated to MGUS compared to general population
* **osteoporosis, thrombosis and bacterial infection**
45
what is plasmacytoma:
soft tissue tumour caused by multipel myeloma plasma cells
46
how does hypercalcaemia present and how can it be treated:
47
common infections in myeloma
chest infections especially **_gram negative_** fungal infections uncommon but can occur in later stages especially after prolonged use of steroids. **Main problem is viral infections** especially herpes zoster reactivation- shingles is very common
48
treatment for transplant eligible patients and ineligible patients
NB: only autologous stem cell transplant is licensed- not allogeniec.
49
Mechanisms by which Multiple Myeloma and Kidney Injury
* Immunoglobulin light chains **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**
50
Main markers presented by B cells vs plasma cells
B Cells: CD19, CD20, surface Ig Plasma Cells CD138, CD38
51
what determines the severity in amyloidossi associated to mylemoma/MGUS
severity of disease does not equate to amount of light chains but type of misfolding amyloidogenic potential of light chains is more important than their amount
52
how can you test for amyloid deposites in bone marrow
* **congo red staining and under polarised light** * stains as pinky/reddish on Congo red * green apple colour in polarised light
53
which light chian is amyloidosis commonly associated to in myeloma/MGUS
lambda light chain
54
summarise the investiations done for multiple myeloma
55
what percentage of plasma cells do you see the bone marrow in multiple myeloma?
\>10%
56
WHat staging system is used for MM?
durie salmon
57
Treatment if MM
58
M spike in MGUS vs SM vs MM
MGUS: \<30 SM: \>30 MM: \>30
59
Bone marrow clonal plasma cells MGUS vs SM vs MM
MGUS: \<10% SM: \>10% MM: any clonal plasma cell population; automatically diagnostic of \<60% plasma cells
60
CRAB features in MGUS vs SM vs MM
ONLY PRESENT IN MM
61
Organ damage in MGUS vs SM vs MM
ONLY IN MM hypogammaglobuulinaemia occult bone disease hypervisoccity cytopenia
62
MGUS vs SM vs MM : which one needs treatment?
only MM
63
Summary of MGUS vs SM vs MM
64
what is another name of waldernstrom's macroglobulinaemia?
Lymphoplasmacytoid Lymphoma - LPL
65
Who gets waldenstrom's macroglobulinaemia?
elderly men typically
66
presentation of waldenstrom's
Low-grade NHL; lymphoplasmacytoid cells producing monoclonal serum IgM infiltrate the LNs/BM Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness) Treatment: plasmapheresis for hyperviscosity; rituximab / bendamustine or ibrutinib for active disease
67

Haematology (16 decks)

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