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Hematology > 107 Multiple Myeloma > Flashcards

107 Multiple Myeloma Flashcards

1
Q

A 69M complains of bone pain and easy fatigability. Labs: creatinine 2.5 mg/dl, hemoglobin 8 mg/dl, serum calcium 12 mg/dl, serum M component and bone marrow plasmacytosis. What is the cause of the bone lesions of this patient?
A. Apoptosis of tumor cells
B. Activation of osteoclasts
C. Activation of osteoblast that form new bone
D. Hypercalcemia

A

B. Activation of osteoclasts

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2
Q

Monoclonal neoplasm a related to each other by virtue of their development from common progenitors in the late B lymphocytes lineage

A

Plasma cell disorder

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3
Q

What composes plasma cell disorders?

A

Multiple myeloma
Waldenstroms macroglobulinemia
Primary amyloidosis
Paraproteinemias/monoclonal gammopathies

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4
Q

What are the heavy chain isotypes and light chain isotopes?

A

Heavy chain isotopes: M, G, A, D, E

Light chain isotopes: kappa, lambda

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5
Q

What are the 3 structural variation of immuboglobulins?

A

Isotopeas
Allotypes
Idiotypes

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6
Q

Distinguish between main classes of antibodies of a given species

A

Isotypes

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7
Q

Reflect differences between individuals of the same species of otherwise similar immunoglobulins

A

Allotypes

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8
Q

Formed by unique structure of the antigen binding protein portion of the molecule

A

Idiotypes

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9
Q

Forms the antigen recognition site of the antibody molecule

A

Variable region
VDJ: heavy chain
VJ: light chain

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10
Q

Which antibody molecule is produced in excess and excreted in the kidneys?

A

Light chains

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11
Q

Sharp spike in this region during electrophoresis in association with plasma cell disorders and an excellent tumor maker to manage therapy

A

M component

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12
Q

Two rare skin disorders associated with monoclonal gammopathy

A

Lichen myxedematosus

Necrobiotic xanthogranuloma

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13
Q

Most common serum concentration in the heavy chain class

A

IgG are more common than IgA and IgD myelomas

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14
Q

Malignant proliferation of plasma cells derived from a single clone

A

Multiple myeloma

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15
Q

What is the error found in multiple myeloma?

A

Errors in switch recombination, genetic mechanism to change antibody heavy chain isotypes in the early transformation process

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16
Q

Common mutations in multiple myeloma

A

N Ras
K Ras
B raf

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17
Q

Interluekin that play a role in driving myeloma cell proliferation?

A

Interluekin 6 (IL6)

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18
Q

Mean age of diagnosis of MM

A

Mean age of diagnosis is 69 years old and uncommon under age 40

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19
Q

Most common symptom of myeloma

A

Bone pain

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20
Q

What causes the pain in myeloma

A
  1. Proliferation of tumor cells
  2. Activation of osteoclasts that destroy bone
  3. Suppression of osteoblast that form new bone
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21
Q

Second common clinical problem in patient with myeloma

A

Susceptibility to bacterial infection

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22
Q

Common infections in multiple myeloma

A

Pneumonias

Pyelonephritis

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23
Q

Most frequent pathogens in myeloma

A

Strep pneumoniae
Staph aureus
Kleb pneumoniae

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24
Q

Most common cause of renal failure in multiple myeloma

A

Hypercalcemia

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25
Q

Earliest manifestation of tubular damage in multiple myeloma

A

Adult fanconi syndrome: type 2 proximal renal tubular acidosis; loss of Glucose and amino acids as well as defects in the ability to acidify and concentrate urine

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26
Q

True or false. In multiple myeloma, very little albumin is in the urine because glomerular function is usually normal

A

True

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27
Q

Multiple myeloma is result with what type of anion gap and why?

A

Patients with multiple myeloma have decreased an anion gap because M component is cationic, resulting in retention of Chloride

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28
Q

Why type of electrolyte imbalance accompany multiple myeloma?

A

Pseudo Hyponatremia because each volume of serum has less water as a result of increased protein

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29
Q

True or false. Light chain cast nephropathy and amyloidosis is partially reversible with effective therapy

A

True

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30
Q

True or false. Patients with multiple myeloma are susceptible to developing AKI when dehydrated

A

True

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31
Q

Type of anemia in multiple myeloma. What’s is the cause of this anemia?

A

Normocytic normochromic anemia

Due to replacement of normal marrow by expanding tumor cells

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32
Q

Pathophysiology of Clotting abnormalities in multiple myeloma

A

Failure of the antibody-coated platelets to function properly

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33
Q

What Clotting factors are affected in multiple myeloma?

A 
Clotting factors I, II, V, VII, or VII
2,3
2+3=5
5+2=7
5+3=8
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34
Q

Normal relative serum viscosity

A

1.8

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35
Q

What is hyperviscosity?

A

Relative viscosity of serum as compared to water

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36
Q

When does symptoms of hyperviscosity occur?

A

4.0 centipoise (cP)

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37
Q

When is hyperviscosity reached in patients with multiple myeloma?

A

IgM: 40 g/dl or 4 g/L
IgG3: 50 g/dl
IgA: 70 g/dl

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38
Q

What type of neuropathy is associated with multiple myeloma?

A

More sensory than motor and is associated with IgM

IgM targets myelin-associated Globulin

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39
Q

Defines the diagnosis of multiple myeloma

A

Marrow plasma cytosis of more than 10%
Serum/urine M protein
*least one of the myeloma defining events

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40
Q

What is the character of bone marrow plasma cell in multiple myeloma?

A

CD138+ and either

Kappa and lambda light chain positive

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41
Q

Important differential diagnosis of patients with multiple myeloma

A

MGUS

smoldering multiple myeloma (SMM)

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42
Q

True or false. All cases of MGUS transform to multiple myeloma

A

False. Only 1% transform to multiple myeloma

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43
Q

True or false. All multiple myeloma preceded by MGUS

A

True

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44
Q

Associated with higher incidence of progression of MGUS to multiple myeloma

A

Non IgG subtype
Abnormal kappa/lambda ratio
Serum M protein more than. 15 g/dl (1.5 g/L)

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45
Q

Associated with higher incidence of progression of MGUS to multiple myeloma

A

Non IgG subtype
Abnormal kappa/lambda ratio
Serum M protein more than. 15 g/dl (1.5 g/L)

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46
Q

Features responsible for higher incidence of progression from SMM to MM

A

Bone marrow plasmacytosis more than 10%
Abnormal kappa/lambda free light chain rario
Serum M protein more than 30 g/L (3.0 g/dl)

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47
Q

Two important variants of multiple myeloma

A

Solitary bone plasmacytoma

Solitary extramedullary plasmacytoma

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48
Q

Single lytic bone lesion without marrow plasmacytosis

A

Solitary bone plasmacytoma

49
Q

Variant of multiple myeloma that involve submucosal lymphoid tissue of the nasopharybx or Paranasal sinuses without marrow plasmacytosis

A

Extramedullary plasmacytoma

50
Q

True or false. Both solitary bone plasmacytoma and extramedullary plasmacytoma are highly responsive to local radiation therapy

51
Q

True or false. Extramedullary plasmacytoma recur often and progresses to multiple myeloma

A

False
Extramedullary plasmacytoma: rarely recurs and rarely progress to multiple myeloma
Solitary bone plasmacytoma: recurs often and may evolve to multiple myeloma

52
Q

What is usual level of serum alkaline phosohatase and why?

A

Serum alkaline phosohatase is usually normal even with extensive bone involvement because of the absence of osteoblastic activity

53
Q 
Myeloma that may present with light chain disease
A. IgM
B. IgG
C. IgD
E. IgA
54
Q

Why will some patients with multiple myeloma had negative Bence Jones protein

A

Renal cataboismbwikk make light chains undetectable in urine

55
Q

What type of light chain is more likely to cause renal damage

A

Kappa light chain

56
Q

Multiple myeloma paraprotein associated with hyperviscosity

57
Q

Subclass of multiple myeloma that has the highest tendency to form both concentration and temperatures dependent aggregates leading to hyperviscosity and cold agglutination at lower serum concentrations

58
Q

Recommended to distinguish between smoldering and acrivibe MM and to confirm suspected diagnosis of solitary plasmacytoma

A

F Fluorodeoxyglucose PET/CT

59
Q

Single most powerful predictor of survival and can substitute for staging

A

Serum B2 microglobulin

60
Q

Forms the basis for the three-stage International Staging System (ISS) that predicts survival

A

Serum B2 microglobulib and albumin levels

61
Q

ISS. B2M less than 3.5. Alb more than 3.5

A

Stage I. Survival 62 months

62
Q

ISS. B2M less than 3.5. Albumin less than 3.5 or B2M =3.6-5.5

A

Stage II. 44 months

63
Q

ISS. B2M more than 5.5

A

Stage III. 29 months

64
Q

Other features suggesting high risk disease

A

De novo plasma cell leukemia
Extramedullary disease
Elevated LDH
High risk gene expression profile

65
Q

Median number of mutations per transcribed genome in myeloma

66
Q

Most frequently mutated gene in multiple myeloma

A 
KRAS and NRAS
TP53
DIS3
FAM46C
BRAF
67
Q

How frequent is the follow up in patients with MGUS

A

Low risk: Once a year

High risk: every 6 months

68
Q

May prevent progression from high risk SMM to active MM.

A

Early intervention with lenalidomide and dexamethasone

69
Q

Solitary bone plasmacytoma and extramedullary plasmacytomas may be expected to enjoy prolonged disease free survival after what therapy?

A

Local radiation therapy at a dose of around 40 Gy

70
Q

Purpose of therapy in multiple myeloma

A
  1. Systemic to control myeloma

2. Supportive to control symptoms

71
Q

What are the phases of therapy in multiple myeloma

A
  1. Induction
  2. Consolidation/maintenance
  3. Relapse
72
Q

Therapy that achieves response in two-thirds of newly diagnosed MM patients

A

Thalidomide + dexamethasone

73
Q

Combination which achieved high response rate of 80% in patient with multiple myeloma and a 30% complete remission

A

Lenalidomide + bortezumib + dexamethasone

74
Q

Other 3 drug combination therapy for multiple myeloma

A

Bortezumib + thalidomide + dexamethasone

Bortezumib+ cyclosphosphamide + dexamethasone

75
Q

Indicated if bortezumub is used

A

Herpes zoster prophylaxis

76
Q

Lenalidomide requires additional prophylaxis for what?

A

Lenalidomide required DVT prophylaxis with aspirin

If at greatest risk for DVT, warfarin or LMWH

77
Q

Therapy given to all stages of multiple myeloma

A

Steroid: dexamethasone or prednisone

78
Q

Therapy for newly diagnosed MM

A

Immunomodulatory: thalidomide
Proteasime inhibitor: bortezomib
Alkylating agents: melphalan, cyclophosphamide

79
Q

Standard therapeutic agents in myeloma

A

6

  1. Immunomodulatory: thalidomide, lenalidomide
  2. Proteasome inhibitors: bortezomib, carfilzomib, ixazomib
  3. Antibodies: daratumumab, elotuzumab
  4. Histone deacetylase inhibitor: panobinostat
  5. Alkylating agents: melphalan, cyclosphosphamide, bendamustine
  6. Steroids: dexamethasone, prednisone
80
Q

Only histone deacetylase inhibitor for MM

A

Panobinostat

81
Q

Standard therapeutic agents given only on relapse

A

Antibodies

Histone deacetylase

82
Q

Avoid in patients for autologous transplant

A

Alkylating agents such as melphalan as it decrease ability to collect stem cells for autologous transplant

83
Q

Who are not transplant eligible?

A

Age more than 70 years old

Significant cardiopulmonary problems or comorbid illness

84
Q

Newly diagnosed MM. Transplant eligible.

A

Induction therapy:
RVD: lenalidomide, bortezumib, dexamethasone
VCD: bortezomib, cyclosphosphamide, dexamethasone
VD: bortezomib, dexamethasone
LD:

85
Q

Newly diagnosed MM. Transplant eligible. Response to induction therapy.

A

HDT with ASCT

High dose therapy + autologous stem cell transplant

86
Q

Newly diagnosed MM. Transplant eligible. No response to induction therapy.

A 
Alternative regimen:
Daratumumab
Elotuzumab
Panobinostat
Carfilzomib
Ixazomib
Pomalidomide
87
Q

Newly diagnosed MM. Transplant ineligible.

A

Induction therapy
RVD lite: lenalidomide, bortezumib, dexamethasone weekly
VCD: bortezomib, cyclosphosphamide, dexamethasone
VD: bortezomib, dexamethasone
RD: lenalidomide, bortezumib

88
Q

Drug for MM, antibodies that target CD3i

A

Daratumumab

89
Q

Drug for MM that target SLAMF7

A

Elotuzumab

90
Q

True or false. Improvement in serum M component lag being the symptomatic improvement due to long half life of about 3 weeks

91
Q

May fall during the first week of treament due to short half life

A

Light chain excretion. Half life is 6 hours

92
Q

Predicts longer survival in MM

A

Absence of minimal residual disease (MRD) on sequencing or multicolor flow cytometry

93
Q

Mean overall survival of patients with multiple myeloma

94
Q

Major cause of death in multiple myeloma

A

Renal failure
Sespsis
Progressive multiple myeloma
Therapy related myelodysplasia

95
Q

Treatment of hypercalcemia in multiple myeloma

A

Biphosphonates: reduces osteoclastic bone resoprtion
Glucocorticoids
Hydration
Natriuresis

96
Q

Adverse effect of biphosphonates

A

Osteonecrosis of jaw and renal dysfunction

97
Q

During acute renal failure in patients with MM, what therapy is 10x more effective in clearing light chains

A

Plasmapharesis is 10x more effective at clearing light chains than peritoneal dialysis

98
Q

Treatment of choice for hyperviscosity syndromes

A

Plasmapharesis

99
Q

More protective vaccine against pneumonia in patients with MM

A

Pneumococcal conjugate may be more protective as MM patients may not elicit antibody response is given pneumococcal polysaccharide

100
Q

Malignancy of lymphoplasmacytoid cells that secrete IgM

A

Waldenstroms macroglobulinemia

101
Q

Differentiate MM from Waldenstroms macroglobulinemia

A

Waldenstroms macroglobulinemia: Lymphadenopathy, hepatosplenomegaly and hyperviscosity syndrome, no lytic bone lesion, no hypercalcemia

102
Q

Difference between Waldenstroms macroglobulinemia and IgM myeloma

A

IgG myeloma: patients with lytic bone lesions and predominant infiltration with CD138+ plasma cells in the bone marrow

103
Q

Somatic mutation seen in Waldenstroms macroglobulinemia

A

MYD88 L265P

104
Q

Presence of this mutation status used to discriminate WM from marginal zone lymphoma, IgM secreting myeloma and CLL with plasmacytic differentiation

A

MYD88 mutation

105
Q

Significant mutation in WM. Why?

A

MYD88: lower bone marrow burden
CXCR4: higher bone marrow birder and higher incidence of hyperviscosity

106
Q

First line treatment for WM

A

Rituximab: Anti CD20
Alkylators: bendamustine, cyclosphosphamide
Proteasome inhibitors: bortezomib

107
Q

Used for patients with WM and target the BTK (Burton tyrosine kinase)

A

Irbrutinib

108
Q

Syndrome presenting wiht polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes

109
Q

Condition linked to IL 6 overproduction

A

Castleman disease

110
Q

Defect in heavy chain diseases

A

Intact Fc fragment and deletion in the Fd region

111
Q

Franklin’s disase is frequently associated with what autoimmune disease

A

Rheumatoid Arthritis

112
Q

What are the heavy chain diseases

A

Gamma heavy chain disease: Franklins disease
Alpha heavy chain disease: Seligmann’s disease
Mu heavy chain disease

113
Q

Most distinctive symptom of Gamma heavy chain disease

A

Palatal edema due to involment of nodes in the Waldeyers ring

114
Q

Most common of the heavy chain diseases and what is it closely related to

A

Alpha chain disease or Seligmann’s disease

Closely related to mediterranean lymphoma

115
Q

How is alpha heavy chain disease characterized

A

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

116
Q

Recognized as infectious pathogen assosciated human lymphoma and what is the pathogen

A

Immunoproliferative small intestinal disease (IPSID),

Campyobacter jejuni

117
Q

Characterize mu heavy chain disease

A

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

118
Q

What is the defect in Mu heavy chain disease

A

Defect in the assembly of light and heavy chain

Hematology (11 decks)

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