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Heme/Lymph Exam 2 (Erik Hammond) > Lecture 10: Plasma Cell Disorders > Flashcards

Lecture 10: Plasma Cell Disorders Flashcards

1
Q

Essential monoclonal gammopathy (aka MGUS) is most commonly seen in what age group and is more prevalent in which ethnicity?

A
  • Occur in older pt’s >50 y/o
  • 2-3x more common in pt’s of African descent
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2
Q

Essential monoclonal gammopathy (aka MGUS) is defined by what 2 key features?

A
  • Presence of a monoclonal Ig or monoclonal Ig light chain in serum
  • Absence of evidence for an overt malignancy of B lymphocytes or plasma cells (i.e., lymphoma, myeloma, or amyloidosis)
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3
Q

How is essential monoclonal gammopathy (aka MGUS) best managed?

A
  • Long term follow-up at appropriate intervals to detect conversions from a stable asymptomatic condition to a progressive lymphoma or myeloma
  • In absence of symptomatic gammopathy, periodic follow-up is all that’s required
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4
Q

Multiple myeloma should be considered in pt’s with what signs/sx’s?

A
  • Anemia, fatigue, weight loss, bone pain
  • Pathological fractures, lytic bone lesions
  • Hypercalcemia
  • Kidney failure
  • Recurrent infections (particularly pneumococcal)
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5
Q

Which plasma cell tumor may arise in some pt’s with multiple myeloma and what complications can this lead to?

A

Plasmacytomas; if in vertebrae, ↑ risk of spinal cord compression

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6
Q

The large number of M proteins in the blood of pt with multiple myeloma lead to what abnormal finding on blood smear?

A

Rouleaux formation = red cells sticking together

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7
Q

Evaluation of multiple myeloma begins with what 2 tests?

A

Serum protein electrophoresis and urine protein electrophoresis on a 24-hour urine sample

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8
Q

After serum electrophoresis what other labs/tests should be ordered for suspected multiple myeloma?

A
  • CBC
  • Radiographic bone survery
  • Serum creatinine, BUN, and calcium levels
  • Bone marrow aspirate and biopsy
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9
Q

Why are bone scans not obtained for dx of multiple myeloma?

A

Because myeloma lesions are usually lytic and lack assoc. increase in osteoblast activity that leads to (+) bone scans

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10
Q

Why is β2-microglobulin and LDH important for the diagnosis of multiple myeloma?

A

Measures tumor burden

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11
Q

Which chromosomal abnormality is associated with shorter disease-free and overall survival in multiple myeloma pt’s?

A

Deletion of the long arm of chromosome 13

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12
Q

What does a bone marrow plasma cell labeling index measure and why is it useful in multiple myeloma?

A

Specifically measures plasma cell proliferation; prognostic for survival

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13
Q

What should always be in the differential of a patient with an A:G ratio <1?

A

Plasma cell disorder (MGUS, myeloma, etc,)

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14
Q

What is treatment for MGUS and pt’s with myeloma who lack any end-organ damage and who are asymptomatic?

A

No treatment; just observation

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15
Q

Which serum β2-microglobulin level is considered stage III and poor prognosis for myeloma?

A

>5.5 mg/L

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16
Q

What is considered the best therapy for multiple myeloma and who should it be used for?

A

Autologous stem cell transplantation; pt’s <75 y/o with good performance status

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17
Q

Beyond advanced age and poor performance, what are 3 contraindications to autologous stem cell transplant in multiple myeloma pt?

A
  • Unstable and progressive kidney disease
  • Decompensated cirrhosis
  • New York Heart Association class III or IV heart failure
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18
Q

What must be done first in multiple myeloma pt’s who are eligible for transplantation therapy?

A

Induction chemotherapy regimen for 2-4 months to reduce tumor burden and to demonstrate responsiveness to chemo

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19
Q

Which chemotherapeutic agents are used for induction therapy in multiple myeloma pt’s prior to transplantation?

A
  • High-dose dexamethasone + thalidomide
  • Newer agents = lenalidomide and bortezomib
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20
Q

Why must thalidomide and lenalidomide be used cautiously in treating women of child-bearing age?

A

Potent teratogens

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21
Q

Multiple myeloma pt’s receiving either thalidomide or lenalidomide with dexamethasone as combination therapy have a very high risk for what; how is this managed?

A
  • Risk for venous thrombombolism
  • Require thromboprophylaxis w/ low-molecular-weight heparin or warfarin
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22
Q

What is the follow-up like for pt with multiple myeloma?

A

Followed on a monthly basis to determine response to therapy and to assess kidney function, blood cell counts, and calcium levels

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23
Q

All pt’s with multiple myeloma receiving prolonged glucocorticoid should receive what prophylactic tx?

A

TMP-SMX to prevent Pneumocystis pneumonia

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24
Q

Pt’s with multiple myeloma who are being treated with bortezomib should be treated prophylactically with what?

A

Acyclovir to prevent reactivation of VZV

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25
Q

What should be given to multiple myeloma patients to decrease bone fractures and bone pain; this tx can only be administered for how long

A

Bisphosphonates (pamidronate or zoledronate); therapy limited to 2 years

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26
Q

Patients with multiple myeloma and back pain need prompt radiographic evaluation with what type of imaging modality; why?

A

MRI, to rule out spinal cord compression

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27
Q

What is an effective palliation therapy for localized bone pain in pt with multiple myeloma?

A

Radiation therapy

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28
Q

How should the acute kidney injury of patient with multiple myeloma be managed; what about when severe?

A
  • Maintain hydration and avoidance of nephrotoxic drugs + contrast dyes
  • Mild hypercalcemia may resolve with hydration alone; this may also improve early AKI
  • Severe kidney injury may require dialysis
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29
Q

Which findings are suggestive of Waldenström Macroglobulinemia in contrast to multiple myeloma?

A
  • Assoc. w/ lymphadenopathy, hepatosplenomegaly and hyperviscosity
  • NO bone lesions or hypercalcemia!
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30
Q

How is IgM myeloma distinguished from Waldenström Macroglobulinemia?

A

Pt’s with lytic bone lesions and predominant infiltration w/ CD138+ plasma cells in the BM

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31
Q

Which distinct somatic mutation is present in >90% of pt’s with Waldenström Macroglobulinemia?

A

MYD88 L265P somatic mutation

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32
Q

What is the role of the MYD88 mutations in the pathogenesis of Waldenström Macroglobulinemia?

A

Triggers Bruton tyrosine kinase, hematopoietic cell kinase growth, and survival signaling

33
Q

What is the basis for some patients with Waldenström Macroglobulinemia developing a peripheral neuropathy before the appearance of a neoplasm?

A

Some pt’s have IgM with specificity for myelin-associated glycoprotein (MAG); which is assoc. w/ demyelinating disease of peripheral nervous system

34
Q

Patients with Waldenström Macroglobulinemia commonly present how, which features are distinct?

A
  • Weakness, fatigure, and recurrent infections (like MM)
  • But epistaxis, visual disturbancesandneurological sx’ssuch asperipheral neuropathy+dizziness+HA+transient paresis=more common
35
Q

How does the presence of CXCR4 mutations vs. MYD88 mutations in Waldenström Macroglobulinemia affect the course of disease?

A
  • CXCR4 is assoc. with higher bone marrow disease burden and higher incidence of hyperviscosity
  • Pt’s with wild-type MYD88 show lower bone marrow disease burden
36
Q

What are common PE findings assoc. with Waldenström Macroglobulinemia?

A
  • Adenopathy and hepatosplenomegaly
  • Opthalmoscopic exam may reveal vascular segmentation and dilation of the retinal veins
37
Q

Which peripheral smear and lab findings associated with Waldenström Macroglobulinemia are much more common than in MM?

A
  • Normocytic, normochromic anemia
  • Rouleaux formation and a (+) coombs test = much more common
  • Malignant lymphocytes usually present in peripheral blood
  • About 10% of macroglobulins are cryoglobulins = pure M cells components
38
Q

Patients suspected of having a cryoglobulin based on hx and PE should have their blood drawn how specifically?

A

Into a warm syringe and delivered to lab in container of warm water to avoid errors in quantitating the cryoglobulin

39
Q

How can control of serious hyperviscosity sx’s such as altered state of consciousness or paresis in pt with Waldenström Macroglobulinemia be achieved?

A

Plasmapheresis

40
Q

What are 4 pretreatment parameters in pt with Waldenström Macroglobulinemia which define a high-risk population?

A
  • Older age
  • Male sex
  • General sx’s
  • Cytopenias
41
Q

What is general tx for pt with Waldenström Macroglobulinemia that is indolent?

A

Generally no therapy

42
Q

When treatment is warranted for Waldenström Macroglobulinemia, which drug can be used to target the constitutively activated Bruton tyrosine kinase?

A

Ibrutinib

43
Q

Other than Ibrutinib, what are the other first-line agents used in symptomatic Waldenström Macroglobulinemia?

A
  • Rituximab (anti-CD20) alone or in combo with:
  • Alkylators (bendamustine or cyclophosphamide)

or

  • Proteasome inhibitors (bortezomib)
  • Fludarabine and Cladribine are also highly effective single agents
44
Q

What are the 4 criteria which must be met for diagnosis of POEMS syndrome?

A
  1. Polyneuropathy
  2. Monoclonal plasma cell proliferative disorder
  3. Any one of the following: (a) sclerotic bone lesions; (b) Castleman’s disease (c) ↑ levels of VEGF
  4. Any one of the following: (a) organomegaly; (b) extravascular volume overload (edema, pleural effusion, ascites); (c) endocrinopathy; (d) skin changes; (e) papilledema; (f) thrombocytosis/polycythemia
45
Q

High circulating levels of what proinflammatory cytokines and low levels of what have been documented in POEMS syndrome?

A
  • High levels of IL-1, IL-6, VEGF, and TNF
  • Low levels of TGF-β
46
Q

Pt’s with POEMS syndrome presenting with isolated sclerotic lesions may have resolution of neuropathic symptoms after what tx?o

A

Local therapy for plasmacytoma w/ radiotherapy

47
Q

What are some of the common endocrine manifestations of POEMS syndrome?

A
  • Amenorrhea in women and impotence + gynecomastia in men
  • Hyperprolactinemia –> papilledema and ↑ CSF pressure
  • Type 2 DM
  • Hypothyroidism and adrenal insufficiency (Cushing syndrome)
48
Q

Gamma heavy chain disease (Franklin disease) affects which individuals and what are the common manifestations; what is its distinctive sx?

A
  • Affects people of all ages
  • Characterized by LAD, fever, anemia, malaise, hepatosplenomegaly and weakness
  • Distinctive sx = palatal edema, which may progress to respiratory compromise!
49
Q

Gamma heavy chain disease (Franklin disease) is frequently assoc. w/ autoimmune disease, especially what?

A

Rheumatoid arthritis

50
Q

Diagnosis of gamma heavy chain disease (Franklin disease) is made how?

A

Demonstration of an anomalous serum M component (often <20 g/L) that reacts with anti-IgG but NOT anti-light chain reagents

51
Q

What is the typical course of the disease for pt’s with gamma heavy chain disease (Franklin disease)?

A

Usually rapid downhill course; however, some pt’s have survived 5 years with chemotherapy

52
Q

When symptomatic what does the therapy for gamma heavy chain disease (Franklin disease) include?

A
  • Chemo combos used in low-grade lymphoma
  • Rituximab has shown some efficacy
53
Q

What is the most common of the heavy chain diseases?

A

Alpha heavy chain disease (Seligmann Disease)

54
Q

Alpha heavy chain disease (Seligmann Disease) is due to what?

A

Infiltration of the lamina propria of the small intestine with lymphoplasmacytoid cells that secrete truncated alpha chains

55
Q

How do pt’s with alpha heavy chain disease (Seligmann Disease) commonly present?

A

Chronic diarrhea, weight loss, and malabsorption + extensive mesenteric and para-aortic adenopathy

56
Q

What is an effective combo therapy for alpha heavy chain disease (Seligmann Disease)?

A

Chemotherapy + antibiotics

57
Q

Immunoproliferative Small-Intestinal Disease (IPSID) is recognized as an infectious pathogen-associated human lymphomas that is associated with what bacteria?

A

Campylobacter jejuni

58
Q

Immunoproliferative Small-Intestinal Disease (IPSID) involves what part of the intestine and is associated with excessive what?

A
  • Mainly the proximal small intestine –> malabsorption, diarrhea, and abdominal pain
  • Excessive plasma cell differentiation and production of truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain
59
Q

How is early stage Immunoproliferative Small-Intestinal Disease (IPSID) treated and what happens if left untreated?

A
  • Eary stage responds to antibiotics (30-70% complete remission)
  • Most untreated pt’s progress to lymphoplasmacytic and immunoblastic lymphoma
60
Q

The secretion of isolated mu heavy chains into the serum appears to occur in a very rare subset of which pt’s?

A

Pt’s with chronic lymphocytic leukemia (CLL)

61
Q

The only features that may distinguish patients with mu heavy chain disease are the presence of what?

A

Vacuoles in the malignant lymphocytes and the excretion of kappa light chains in the urine

62
Q

Diagnosis of mu heavy chain disease requires what?

A

Ultracentrifugation or gel filtration to confirm non-reactivity of the paraprotein with the light chain reagent

63
Q

How are patients with mu heavy chain disease treated?

A

No different from other pt’s with CLL

64
Q

How does AL differ from AA amyloid?

A
  • AL is amyloid composed of Ig light chains; also known as primary amyloidosis and can be assoc. with myeloma or lymphoma
  • AA is acute phase reactant protein serum amyloid A (SAA) and occurs in setting of chronic inflammation or infection; is known as secondary amyloidosis
65
Q

What is the most easily accessible tissue for biopsy and is positive in >80% of patients with systemic amyloidosis?Ad

A

Abdominal fat

66
Q

Amyloid deposits will impart which unique staining characteristic when viewed under light microscopy?

A

“Apple green” birefringence by polarized light microscopy when stained with Congo red dye

67
Q

What are the most frequently involved organ in systemic amyloidosis (AL) and how does this present?

A
  • Kidneys
  • Manifsts as proteinuria (often nephrotic range) and assoc. hypoalbuminemia, 2’ hypercholesterolemia, hypertriglyceridemia + edema or anasarca
  • Some pt’s have interstital deposits prod. azotemia without proteinuria
68
Q

The heart is the 2nd most common organ involved in systemic amyloidosis (AL) and how can this be seen clinically on EKG and other imaging modalities?

A
  • Early on, ECG show low voltage in limb leads with a pseudo-infarct pattern
  • Echocardiographic features, include concentrically thickened ventricles and diastolic dysf. w/ abnormal global longitudinal strain pattern; a “sparkly” appearance
69
Q

Pt’s with cardiac involvement in systemic amyloidosis (AL) are at risk for what complications due to poor atrial contractility?

A

Development of atrial thrombi and stroke

70
Q

What are 2 pathognomonic findings of AL amyloidosis

A
  • Macroglossia (only 10% of pt’s)
  • Cutaneous ecchymoses, particularly around the eye, producing the “raccoon-eye” sign
71
Q

How does splenic involvement in AL amyloidosis present?

A

Functional hypersplenism WITHOUT significant splenomegaly

72
Q

What is key in making the diagnosis of AL amyloidosis?

A

Identification of an underlying clonal plasma cell or B lymphoprolierative process and a clonal LC are key

73
Q

How can serum or urine monoclonal LC or whole immunoglobulin detectable in 90% of AL amyloidosis pt’s be detected?

A
  • Immunofixation electrophoresis of serum or urine or by measurement of serum “free” LC’s
  • Examining the ratio as well as the absolute amount of serum-free LCs is ESSENTIAL
74
Q

Kappa or lambda clonality in pt with suspected AL amyloidosis should be demonstrated how?

A

By flow cytometry, immunohistochemistry, or in situ hybridization for LC mRNA

75
Q

What are some of the aggressive treatment options for pt’s with AL amyloidosis?

A
  • Dexamethasone
  • High-dose IV melphalan followed by autologous stem cell transplant (HDM/SCT) is aggressive tx that is only suitable for minority
  • Cardiac transplant followed by HDM/SCT in those with impaired cardiac function
76
Q

For patients with AL amyloidosis and nephrotic syndrome what is the best supportive methods of tx for edema and to produce diuresis?

A
  • Diuretics and supportive stocking can ameliorate edema
  • Effective diuresis can be facilitated w/ albumin infusions to raise intravascular oncotic pressure
77
Q

CHF and atrial/ventricular arrhythmias due to amyloid cardiomyopathy is best treated how?

A
  • Diuretics for CHF
  • Amiodarone can be used for arrhythmias
  • AVOID digitalis, CCB’s and beta blockers
78
Q

Atrial contraction dysfunction is common in amyloid cardiomyopathy and increases risk for thromboembolic complications, how can this be managed?

A

Consider anti-coagulant even in absence of Afib

Heme/Lymph Exam 2 (Erik Hammond) (21 decks)

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