107 - Plasma Cell Disorders Flashcards
1
Q
What is the best cancer marker for follow up after treatment in plasma cell disorder?
A
M component protein
2
Q
In which cases will you see M-component (5)?
A
- CLL
- CML
- Breast/colon cancer
- Cirrhosis/ sarcoidosis
- Post transplantation
3
Q
Define MM (Multiple Myeloma)
A
Malignant proliferation of plasma cells from a single clone
4
Q
Name 4 risk factors for MM
A
- Radiation
- Pesticide
- Petroleum
- Wood/leather industry
5
Q
What is the most in risk population for MM?
A
- > 70
- Male
- Black
- Industrialized countries
* American old back man
6
Q
Name 6 groups of clinical manifestations in MM
A
- Bone pain
- Infections
- Renal injury
- Anemia
- Coagulation
- Neurological
7
Q
What is the most common symptoms in MM patients?
A
Bone Pain- 70% of patients
8
Q
What causes the lytic fractures in MM patients (3)?
A
- Proliferation of plasma cells in the BM
- Activation of osteoclasts by osteoclast activating factors created by myeloma cells
- Deactivating osteoblasts
9
Q
What is the second most common symptoms in MM patients?
A
Infections with pneumonia and pyelonephritis
10
Q
Name the most common pathogens in MM infections (4)
A
- Strep pneumonia
- Staph aureus
- Klebsiella pneumonia
- E.coli
11
Q
What are the leading factors contributing for infections in MM (3)?
A
- Hypogammaglobulinemia
- Immune cells disfunction (T/granulocytes/complement)
- Iatrogenic due to treatment with dexamethasone
12
Q
In what percentage does kidney injury and renal failure occur in MM?
A
- Kidney injury- 50%
2. RF- 25%
13
Q
What are the contributing factors for renal injury in MM (7)?
A
- Hypercalcemia
- NSAID
- Hyperuricemia
- Recurrent infections
- Amyloid depositions in the glomeruli
- Bisphosphonate
- MM cells infiltration
14
Q
Which chains cause glomeruli injury?
A
Light chain- due to filtration leading to direct toxic effect, and indirectly causing the release of lysosomal intracellular enzymes
15
Q
What are the clinical features of renal injury in MM (6)?
A
- RTA 2- Adult Fanconi
- Proteinuria of mostly light chains and no HTN
- Normal glomeruli function- no albuminuria
- Low anion gap
- Pseudohyponatremia
- RF
16
Q
In what percentage of patients does anemia occur in MM?
A
80%
17
Q
Why do MM patients develop anemia (3)?
A
- Infiltration of MM cells in to the BM
- hematopoiesis inhibitory factors
- Decrease in EPO due to renal injury
18
Q
What kind of anemia does MM cause (2)?
A
- Normocytic- normochromic
2. Megaloblastic (due to B12/folic acid deficiency)
19
Q
What leads to coagulation disorder in MM (3)?
A
- Antibodies attaching to platelets
- M-component interacting with coagulation factors
- Amyloid damage to endothelium
20
Q
Which MM patients are more likely to suffer from DVT?
A
Patients undergoing treatment with thalidomide+ dexamethasone
21
Q
What are the causes for neurological symptoms in MM patients (4)
A
- Hypercalcemia (lethargy, depression, confusion)
- Hyperviscosity (tiredness, headache, dyspnea, HF, retinopathy, vertigo)
- Spinal cord compression
- Amyloid deposition in PNS (carpel tunnel/polyneuropathy)
22
Q
Name the 4 emergencies in MM
A
- Spinal cord compression
- Sepsis
- Hypercalcemia
- Pathological fracture
23
Q
How to diagnose MM (3)?
A
- M component > 10% (CD38+ monoclonal cells with lambda/kappa light chains in BM)
- M component found in urine/serum
- At least one MM defining event
24
Q
What are the risk factors to shift from MGUS to MM (3)?
A
- Non IgG
- High ratio of kappa/lambda light chains
- Serum M component > 15 g/L
* When all of the above occur= 60% for MM in 20 years
25
What are the risk factors to shift from smoldering MM to MM (3**)?
1. Plasmacytosis in BM > 10%
2. High ratio of kappa/lambda light chains
3. Serum M component > 30 g/L
* If one of the above occur= 25% for MM within 5 years
* * If all of the above occur= 76% for MM within 5 years
26
What is solitary bone plasmacytoma?
A single bone lytic injury without plasmacytosis in the BM
27
Define MGUS (3)
1. Serum monoclonal protein (non IgM type) < 30 g/L
2. Clonal bone marrow plasma cells < 10%
3. Absence of myeloma defining events/amyloidosis
28
Define smoldering MM (2)
1. Serum monoclonal protein (IgG/A) >= 30 g/L
or
Urinary monoclonal protein >= 500 mg/24h
2. Absence of myeloma defining events/amyloidosis
29
Define MM (2)
1. Clonal BM plasma cells or biopsy proven bony/extramedullary plasmacytoma
2. Myeloma defining events/amyloidosis
30
What are the myeloma defining events (5)?
1. Hypercalcemia
2. Renal insufficiency
3. Anemia
4. Bone lesion
5. One or more biomarkers of malignancy:
clonal clonal BM plasma cell >= 60%
serum free light chain ratio >=100
>1 focal lesions on MRI
31
What is nonsecretory myeloma (3)?
1. No M protein in serum and/or urine
2. BM clonal plasmacytosis >= 10% or plasmacytoma
3. myeloma related organ or tissue impairment
32
What are the 4 criteria in POEMS syndrome?
1. Polyneuropathy
2. Monoclonal plasma cell proliferative disorder
3. Sclerotic bone lesion/Castleman's/elevated VEGF
4. Organomegaly/extravascular volume overload/endocrinopathy/ skin changes/ papilledema/thrombocytosis/polycythemia
33
Which lab tests are helpful when diagnosing MM (5)?
1. CBC
2. ESR
3. Electrolytes + BUN
4. Protein electrophoresis
5. Urine analysis (Bence Johns)
34
What is the distribution of Ig in MM (4)?
1. IgG- 53%
2. IgA- 25%
3. IgD- 1%
4. Only light chains- 20%
35
Which light chain has worse prognosis?
Lambda- more renal injury and amyloid deposition
36
What is more likely to happen in MM patients with IgM?
50% more hyperviscosity
37
What are the two best prognosis prediction markers?
1. Beta 2 microglobulin
| 2. Albumin
38
What is the ISS (International Staging System) in MM (3)?
1. B2M < 3.5, albumin >= 3.5
2. B2M < 3.5, albumin < 3.5 or B2M = 3.5-5.5
3. B2M > 5.5
39
Describe MGUS treatment (3)
1. Low chance of MM- yearly follow up
2. High chance of MM- 6 months follow up: CBC, protein electrophoresis, creatinine, calcium
3. When severe neuropathy due to MGUS- plasmapheresis + Rituximab in IgM MGUS
40
Describe smoldering MM treatment (2)
1. Only when symptomatic and progressive
| 2. Lenalidomide + dexamethasone
41
Describe solitary bone plasmacytoma/ extramedullary plasmacytosis treatment (2)
1. Local radiation
| 2. When BM is involved- systemic treatment
42
What are the two types of treatments in MM?
1. Systemic- stopping the progression of MM
| 2. Symptomatic- supportive, prevents morbidity due to complications
43
What does the treatment include (3)?
1. Induction > 2. Consolidation and/or maintenance > 3. relapse treatment
44
Which patients are not BM transplantation candidates (3)?
1. Physiological age > 70
2. Substantial cardio-pulmonary problems
3. Comorbidity
45
What drug will we avoid prescribing for transplantation candidates?
Alkylating agents (melphalan)
46
What is the most effective induction treatment?
LBD
1. Lenalidomide
2. Bortezomib
3. Dexamethasone
47
Beside LBD, what are the other 4 induction therapies?
1. Lenalidomide + dexamethasone
2. Bortezomib + dexamethasone
3. Bortezomib + thalidomide + dexamethasone
4. Bortezomib + cyclophosphamide + dexamethasone
48
What is the S/E of bortezomib?
VZV
49
What is the S/E of lenalidomide?
DVT- treat with aspirin/ coumadin/ clexane
50
What is the recommended treatment for the elder?
Thalidomide + prednisone
51
What is the drug of choice for maintenance treatment?
Lenalidomide or lenalidomide + bortezomib
52
What are the most common reasons for mortality in MM (4)?
1. Renal Failure
2. Sepsis
3. Therapy related myelodysplasia
4. Age related co-morbidity (MI, stroke, diabetes)
53
What are the supportive care for MM complications (4)?
1. Hypercalcemia- bisphosphonate, glucocorticoids, diuretics, hydration, calcitonin
2. Iatrogenic renal failure- hydration, plasmapheresis
3. Infections- pneumococcal vaccine, IVIg in recurrent infections
4. Cord compression- Emergency MRI, local radiation, glucocorticoids, emergency decompression surgery
5. Anemia- EPO, iron, B12, folate
54
What is the immunoglobulin secreted in WM (Waldenstorm's Macroglobulinemia)
IgM
55
What are the clinical features in WM (3)?
1. Hyperviscosity
2. Lymphadenopathy
3. Hepatosplenomegaly
56
What is the common age for WM?
64, more men than women
57
How do you differentiate between MM and WM?
In WM there's no lytic injury and hypercalcemia and usually no renal injury
58
What is the most common light chain in WM?
Kappa
59
How do you differentiate between WM and CLL?
In WM there's a somatic mutation- MYD88 L265P
60
what are the symptoms of WM (3)?
1. Recurrent infections
2. Weakness and tiredness
3. Hyperviscosity related symptoms (epistaxis, vision impairment, neurological symptoms)
61
When will WM be considered high risk (4)?
1. Old age
2. Male
3. Symptomatic disease
4. cytopenia
62
What is the recommended treatment for hyperviscosity?
Plasmapheresis
