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SALMAN HARRISON'S > 107 - Plasma Cell Disorders > Flashcards

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

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2
Q

In which cases will you see M-component (5)?

A
  1. CLL
  2. CML
  3. Breast/colon cancer
  4. Cirrhosis/ sarcoidosis
  5. Post transplantation
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3
Q

Define MM (Multiple Myeloma)

A

Malignant proliferation of plasma cells from a single clone

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4
Q

Name 4 risk factors for MM

A
  1. Radiation
  2. Pesticide
  3. Petroleum
  4. Wood/leather industry
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5
Q

What is the most in risk population for MM?

A
  1. > 70
  2. Male
  3. Black
  4. Industrialized countries
    * American old back man
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6
Q

Name 6 groups of clinical manifestations in MM

A
  1. Bone pain
  2. Infections
  3. Renal injury
  4. Anemia
  5. Coagulation
  6. Neurological
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7
Q

What is the most common symptoms in MM patients?

A

Bone Pain- 70% of patients

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8
Q

What causes the lytic fractures in MM patients (3)?

A
  1. Proliferation of plasma cells in the BM
  2. Activation of osteoclasts by osteoclast activating factors created by myeloma cells
  3. Deactivating osteoblasts
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9
Q

What is the second most common symptoms in MM patients?

A

Infections with pneumonia and pyelonephritis

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10
Q

Name the most common pathogens in MM infections (4)

A
  1. Strep pneumonia
  2. Staph aureus
  3. Klebsiella pneumonia
  4. E.coli
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11
Q

What are the leading factors contributing for infections in MM (3)?

A
  1. Hypogammaglobulinemia
  2. Immune cells disfunction (T/granulocytes/complement)
  3. Iatrogenic due to treatment with dexamethasone
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12
Q

In what percentage does kidney injury and renal failure occur in MM?

A
  1. Kidney injury- 50%

2. RF- 25%

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13
Q

What are the contributing factors for renal injury in MM (7)?

A
  1. Hypercalcemia
  2. NSAID
  3. Hyperuricemia
  4. Recurrent infections
  5. Amyloid depositions in the glomeruli
  6. Bisphosphonate
  7. MM cells infiltration
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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

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15
Q

What are the clinical features of renal injury in MM (6)?

A
  1. RTA 2- Adult Fanconi
  2. Proteinuria of mostly light chains and no HTN
  3. Normal glomeruli function- no albuminuria
  4. Low anion gap
  5. Pseudohyponatremia
  6. RF
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16
Q

In what percentage of patients does anemia occur in MM?

A

80%

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17
Q

Why do MM patients develop anemia (3)?

A
  1. Infiltration of MM cells in to the BM
  2. hematopoiesis inhibitory factors
  3. Decrease in EPO due to renal injury
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18
Q

What kind of anemia does MM cause (2)?

A
  1. Normocytic- normochromic

2. Megaloblastic (due to B12/folic acid deficiency)

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19
Q

What leads to coagulation disorder in MM (3)?

A
  1. Antibodies attaching to platelets
  2. M-component interacting with coagulation factors
  3. Amyloid damage to endothelium
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20
Q

Which MM patients are more likely to suffer from DVT?

A

Patients undergoing treatment with thalidomide+ dexamethasone

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21
Q

What are the causes for neurological symptoms in MM patients (4)

A
  1. Hypercalcemia (lethargy, depression, confusion)
  2. Hyperviscosity (tiredness, headache, dyspnea, HF, retinopathy, vertigo)
  3. Spinal cord compression
  4. Amyloid deposition in PNS (carpel tunnel/polyneuropathy)
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22
Q

Name the 4 emergencies in MM

A
  1. Spinal cord compression
  2. Sepsis
  3. Hypercalcemia
  4. Pathological fracture
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23
Q

How to diagnose MM (3)?

A
  1. M component > 10% (CD38+ monoclonal cells with lambda/kappa light chains in BM)
  2. M component found in urine/serum
  3. At least one MM defining event
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24
Q

What are the risk factors to shift from MGUS to MM (3)?

A
  1. Non IgG
  2. High ratio of kappa/lambda light chains
  3. Serum M component > 15 g/L
    * When all of the above occur= 60% for MM in 20 years
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25
Q

What are the risk factors to shift from smoldering MM to MM (3**)?

A
  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
Q

What is solitary bone plasmacytoma?

A

A single bone lytic injury without plasmacytosis in the BM

27
Q

Define MGUS (3)

A
  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
Q

Define smoldering MM (2)

A
  1. Serum monoclonal protein (IgG/A) >= 30 g/L
    or
    Urinary monoclonal protein >= 500 mg/24h
  2. Absence of myeloma defining events/amyloidosis
29
Q

Define MM (2)

A
  1. Clonal BM plasma cells or biopsy proven bony/extramedullary plasmacytoma
  2. Myeloma defining events/amyloidosis
30
Q

What are the myeloma defining events (5)?

A
  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
Q

What is nonsecretory myeloma (3)?

A
  1. No M protein in serum and/or urine
  2. BM clonal plasmacytosis >= 10% or plasmacytoma
  3. myeloma related organ or tissue impairment
32
Q

What are the 4 criteria in POEMS syndrome?

A
  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
Q

Which lab tests are helpful when diagnosing MM (5)?

A
  1. CBC
  2. ESR
  3. Electrolytes + BUN
  4. Protein electrophoresis
  5. Urine analysis (Bence Johns)
34
Q

What is the distribution of Ig in MM (4)?

A
  1. IgG- 53%
  2. IgA- 25%
  3. IgD- 1%
  4. Only light chains- 20%
35
Q

Which light chain has worse prognosis?

A

Lambda- more renal injury and amyloid deposition

36
Q

What is more likely to happen in MM patients with IgM?

A

50% more hyperviscosity

37
Q

What are the two best prognosis prediction markers?

A
  1. Beta 2 microglobulin

2. Albumin

38
Q

What is the ISS (International Staging System) in MM (3)?

A
  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
Q

Describe MGUS treatment (3)

A
  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
Q

Describe smoldering MM treatment (2)

A
  1. Only when symptomatic and progressive

2. Lenalidomide + dexamethasone

41
Q

Describe solitary bone plasmacytoma/ extramedullary plasmacytosis treatment (2)

A
  1. Local radiation

2. When BM is involved- systemic treatment

42
Q

What are the two types of treatments in MM?

A
  1. Systemic- stopping the progression of MM

2. Symptomatic- supportive, prevents morbidity due to complications

43
Q

What does the treatment include (3)?

A
  1. Induction > 2. Consolidation and/or maintenance > 3. relapse treatment
44
Q

Which patients are not BM transplantation candidates (3)?

A
  1. Physiological age > 70
  2. Substantial cardio-pulmonary problems
  3. Comorbidity
45
Q

What drug will we avoid prescribing for transplantation candidates?

A

Alkylating agents (melphalan)

46
Q

What is the most effective induction treatment?

A

LBD

  1. Lenalidomide
  2. Bortezomib
  3. Dexamethasone
47
Q

Beside LBD, what are the other 4 induction therapies?

A
  1. Lenalidomide + dexamethasone
  2. Bortezomib + dexamethasone
  3. Bortezomib + thalidomide + dexamethasone
  4. Bortezomib + cyclophosphamide + dexamethasone
48
Q

What is the S/E of bortezomib?

A

VZV

49
Q

What is the S/E of lenalidomide?

A

DVT- treat with aspirin/ coumadin/ clexane

50
Q

What is the recommended treatment for the elder?

A

Thalidomide + prednisone

51
Q

What is the drug of choice for maintenance treatment?

A

Lenalidomide or lenalidomide + bortezomib

52
Q

What are the most common reasons for mortality in MM (4)?

A
  1. Renal Failure
  2. Sepsis
  3. Therapy related myelodysplasia
  4. Age related co-morbidity (MI, stroke, diabetes)
53
Q

What are the supportive care for MM complications (4)?

A
  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
Q

What is the immunoglobulin secreted in WM (Waldenstorm’s Macroglobulinemia)

A

IgM

55
Q

What are the clinical features in WM (3)?

A
  1. Hyperviscosity
  2. Lymphadenopathy
  3. Hepatosplenomegaly
56
Q

What is the common age for WM?

A

64, more men than women

57
Q

How do you differentiate between MM and WM?

A

In WM there’s no lytic injury and hypercalcemia and usually no renal injury

58
Q

What is the most common light chain in WM?

A

Kappa

59
Q

How do you differentiate between WM and CLL?

A

In WM there’s a somatic mutation- MYD88 L265P

60
Q

what are the symptoms of WM (3)?

A
  1. Recurrent infections
  2. Weakness and tiredness
  3. Hyperviscosity related symptoms (epistaxis, vision impairment, neurological symptoms)
61
Q

When will WM be considered high risk (4)?

A
  1. Old age
  2. Male
  3. Symptomatic disease
  4. cytopenia
62
Q

What is the recommended treatment for hyperviscosity?

A

Plasmapheresis

SALMAN HARRISON'S (163 decks)

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