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House Hemat > Multiple Myeloma > Flashcards

Multiple Myeloma Flashcards

1
Q

Paraprotein

Immunoglobulin produced from ____________ of plasma cells( _______ antibody or ___ protein ) is called a paraprotein.

A

a single clone

monoclonal; M

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2
Q

When a paraprotein is present in plasma in excessive amount, it is referred to as _______________.

A

paraproteinaemia

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3
Q

Paraprotein

Paraproteinaemias are usually as a result of ___________ of ____-cells which (lose or retain ?) their ability to mature into plasma cells.

A

clonal transformation

B

Retain

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4
Q

“M” in M protein for ________

A

monoclonal

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5
Q

Paraproteinaemias

_______geneous group of disorders characterized by abnormal proliferation of a single clone of plasma cells (or B lymphocytes), associated with the presence of excessive amount of __________ or __________ in the serum and/or urine.

A

Hetero

monoclonal Immunoglobulin

its fragments

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6
Q

Paraproteinemias may be categorized according to the type of monoclonal protein found in blood:
1. _______ only (or _________).

  1. ________ only
  2. _________
A

Light chains ; Bence Jones protein

Heavy chains

Whole immunoglobulins

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7
Q

Paraproteinaemias

  1. Light chains only : This may be associated with __________ or _________
  2. Heavy chains only (also known as “ _____________ “)
  3. Whole immunoglobulins- “__________ “.
A

multiple myeloma ; AL amyloidosis

heavy chain disease

M-protein

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8
Q

Classification of Paraproteinaemias

Mnemonic = __________

Now , list them

A

MP MoW HP

Malignant monoclonal gammopathies
Plasmacytoma
Monoclonal gammopathy of undetermined significance
Waldenstrom’s macroglobulinemia
Heavy chain disease
Primary amyloid

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9
Q

Malignant monoclonal gammopathies

i)___________
ii)_____________
iii) _______ leukaemia
iv)_______ myeloma
v)__________ myeloma (_____ Syndrome)

A

Multiple myeloma

Smoldering multiple myeloma

Plasma cell

Nonsecretory

Osteosclerotic; POEMS

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10
Q

Malignant monoclonal gammopathies

Multiple myeloma (____,____,_____,_____, and _________)

A

IgG, IgA, IgD, IgE and free light chain

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11
Q

Plasmacytoma
i) _______ plasmacytoma of _____/ __________ plasmacytoma

A

Solitary; bone

extramedullary

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12
Q

MGUS

The following criteria must be met:

Serum monoclonal protein: ___ g/dL

Clonal bone marrow plasma cells: ____ %

(Presence or Absence?) of end-organ damage

A

<3

<10

Absence

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13
Q

end-organ damage such as

_______
_________
__________
___________(CRAB)

A

hypercalcemia, renal insufficiency, anemia, and bone lesions

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14
Q

Smoldering multiple myeloma

The following criteria must be met:

Serum monoclonal protein:____ g/dL

clonal bone marrow plasma cells: ____%

(Presence or Absence?) of end-organ damage

A

3

10

Absence

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15
Q

Smoldering multiple myeloma is also referred to as ___________ multiple myeloma

A

asymptomatic

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16
Q

In Smoldering multiple myeloma

Serum monoclonal protein is usually Ig__ or Ig___

A

G or A

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17
Q

Multiple myeloma is a neoplastic plasma-cell disorder that is characterized by ______________ of (benign or malignant?) plasma cells in the _______, _______ in the blood or urine, and associated ________

A

clonal proliferation

malignant

bone marrow

monoclonal protein

organ dysfunction.

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18
Q

_______ is the most common and important monoclonal gammopathy

A

Multiple myeloma

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19
Q

Multiple myeloma

usually presents as ______ throughout the ______ system.

A

multiple tumour masses

skeletal

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20
Q

Epidemiology of multiple myeloma

It accounts for ____% of all haematological malignacies and ___% of all cancers.

A

10; 1

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21
Q

Epidemiology of multiple myeloma

The incidence is (lower or higher?) among blacks.

Median age at diagnosis is ____ years.

A

Higher

67

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22
Q

Epidemiology of multiple myeloma

There is a slight (male or female?) predominance.

A

male

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23
Q

Epidemiology of multiple myeloma

•It accounts for ___% of all haematological malignacies and ___% of all cancers.

•The incidence is (lower or higher?) among blacks.

•Median age at diagnosis is ___ years.

•There is a slight (male or female?) predominance.

A

10; 1

Higher

67

Male

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24
Q

Etiologic factors multiple myeloma- #OECGM !
The aetiology of multiple myeloma is unknown and several associated risk factors include:
1)________ factor
2)_______ factor
3)________ stimulation
4) _______ abnormalities
5)_____________

A

Occupational

Environmental

Chronic antigenic

Genetic

Monoclonal Gammopathies of Undetermined Significance (MGUS)

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25
Q

Etiologic factors of multiple myeloma - #OECGM !

1) Occupational factor (prolonged ____________ exposure of those living near nuclear facilities and workers in agriculture, metal, rubber, wood, leather, paint and petroleum industries).

A

Low -grade radiation

26
Q

Etiologic factors of multiple myeloma- #OECGM !

Chronic antigenic stimulation ( _______,_________, and ________ e.g Human herpes virus 8 and hepatitis C are aetiological pathogens in multiple myeloma).

A

repeated infections, allergic conditions, autoimmune diseases

27
Q

Etiologic factors of multiple myeloma- #OECGM !

Genetic abnormalities (deletions [13q14 del, 14q32] and translocations t(11:14)(q13:q32), and t(4:14) are most common).

A

Okay?🌚🌚

28
Q

Pathogenesis
Three (3) primary processes lead to the complex disruption of organs in multiple myeloma:

_______________ in Bone marrow

__________ of monoclonal immunoglobulin

_________ of _________

A

Plasma cell expansion

Overproduction

Overproduction of various cytokines

29
Q

Pathogenesis of multiple myeloma: Plasma cell expansion in BM

i) Plasma cell establishes a malignant clone.
ii) Normal BM is ____________. ____ease in the number of normal blood cells leads to _______.

iii) Expanding plasmacytoma in the bone marrow frequently cause ___________________

A

gradually replaced by the slowly expanding malignant clone.

Decr; pancytopenia

bone surface “cortex” destruction.

30
Q

Pathogenesis of multiple myeloma: Overproduction of monoclonal Ig

i)_______________ and other cellular oncogenic events lead to clonal neoplastic plasma cell transformation.

ii) Failure of _______ occurs.

iii) This results in piling up of a clone of plasma cells with marked overproduction of a single antibody that appears in the plasma as ________. Which could be _________ (____,_____ rarely- ______ and _____ ) and part of Ig molecule - free ______________

vi) Some light chains have the property to accumulate as ____________ in various organs.

A

Chronic B-cell Ag stimulation

apoptosis; M- protein

intact immunoglobulin

IgG, IgA ; IgD and IgE

light chains kappa or lambda.

amyloid deposits

31
Q

Note, in multiple myeloma

Free light chains pass through the ________, accumulate in the kidney parenchyma resulting in _________

A

glomerular basement membrane

renal dysfunction.

32
Q

Pathogenesis of multiple myeloma: Overproduction of various cytokines

i) Activation of ______ by the clonal plasma cells.
ii) Sequential release of chemokines such as ____,_____ ,______, and _____

iii) MIP is associated with the upregulation of ______ and downregulation of _____

A

osteoclasts

IL-1, TNF, IL-6, macrophage
inflammatory protein (MIP).

RANKL; OPG

33
Q

RANKL , receptor activation of __________ ligand

OPG (__________ ), a _______ of __________

A

NF-kappabeta

osteoprotegerin

natural antagonist of RANKL

34
Q

Pathogenesis of multiple myeloma: Overproduction of various cytokines

Overexpression of RANKL is associated with increased generation of ______ from _________

This leads to _______ ( _______,_________, and _____________).

A

osteoclast

monocyte precursors.

bone destruction

lytic bone lesions, pathological fractures and osteoporosis

35
Q

Clinical features of multiple myeloma -
#BARR !

1)_____ pain (especially ______)
2)______ features
3)_____ failure
4) Recurrent ______

A

Bone; back ache

Anemia

Renal

infections

36
Q

Clinical features of multiple myeloma -
#BARR !

1) Bone pain (especially back ache) resulting from _________ and ________

2) Anemia features include _____,_____,_____, and ______

A

pathological fractures and vertebral collapse.

fatigue, pallor, palpitations and shortness of breath.

37
Q

Clinical features of multiple myeloma -
#BARR !

Renal failure
causes:

i)_______

ii) ________ deposition (_______ protein) in renal tubules

iii) _______

iv) renal infections

v) Metastatic disease to ______

A

hypercalcemia

light chain ; Bence jones

amyloidosis

interstitium

38
Q

Clinical features of multiple myeloma -
#BARR !

Recurrent infections
causes: i) ______ , ii) suppressed ________ immunity due to ____________________[

A

neutropenia

humoral

low production of normal immunoglobulins

39
Q

Clinical features of multiple myeloma (Cont’d)- #BNAHH

Bleeding
causes:_______, abnormal _____ function, abnormal coagulation -the paraprotein _________ and _________ and interferes with their functions.

A

thrombocytopenia

platelet

covers the platelets’ surface

absorbs the clothing factors

40
Q

Clinical features of multiple myeloma (Cont’d)- #BNAHH!

Hyperviscosity syndrome (especially in Ig__ MM): _____,______,______, and _____

Hypercalcemia: _____, headache, ____uria, weakness, coma

A

A

headache, blurred vision, bleeding and coma.

thirst

poly

41
Q

Clinical features of multiple myeloma (Cont’d)- #BNAHH!

Neurological symptoms: peripheral _______, vertebral ______, and spinal cord ________.

Amyloidosis: (common or rare?) complication

A

polyneuropathies

fracture; compression

Rare

42
Q

Laboratory findings - #HBR ! A) Haematology

i) Full blood count; this will show evidence of ______,______, and _______ with progression of the disease.

ii) Peripheral blood film: usually, this will show _____cytic ____chromic anemia. Evidence of _______ formation (red cell adhering to one another) due to _________

A

Anemia, leukopaenia and thrombocytopenia

normo; normo

rouleaux
increased immunoglobulin.

43
Q

Laboratory findings - #HBR ! A) Haematology

ESR: ____eased because of _________

Bone marrow aspiration and biopsy: shows ____eased plasma cells and tissue _________.

A

incr; high immunoglobulin level.

incr

plasmacytoma

44
Q

Laboratory investigations for multiple myeloma

_________ and __________ - determines the structural types of monoclonal protein (IgG, IgA, IgD, IgE, IgM/ and the type of the light chain / lambda or kappa).

A

Immunofixation and Immunoelectrophoresis

45
Q

Laboratory findings - #HBR !

Abnormal renal function - serum ______ increase, _____ and _____ often increase.

A

creatinine; uric acid and urea

46
Q

Laboratory findings - #HBR !

Serum __________ globulin increase.

Serum calcium ____ease and Proteinuria.

A

β-2 micro

incr

47
Q

Laboratory findings - #HBR !

Urine studies:______ urine collection for Bence Jones proteinuria.

A

24 Hours

48
Q

Laboratory findings of multiple myeloma - #HBR !

Radiological examination
i) Skeletal survey in the ____ skeleton for _________ or __________ using MRI, CT-scan and PET-scan.

A

axial

osteolytic bone lesions

punched-out lytic lesions

49
Q

Diagnostic criteria
International Myeloma Working Group (IMWG) Criteria:

Evidence of organ or tissue impairment (CRAB)

[C] Hypercalcemia (serum calcium _______ mg/dl )

[R] Renal insufficiency (serum creatinine _____ mg/dl) or ______ umol/L (CF : 0.013)

[A] Anemia (Hemoglobin _____ g/dl or 2 g < normal)

[B] Radiologic evidence of ______

A

≥ 11.5

> 2; > 153

<10

lytic bone lesions

50
Q

Diagnostic criteria for multiple myeloma
International Myeloma Working Group (IMWG) Criteria:

i) Presence of serum and/or urine ______

ii) Bone marrow clonal plasma cells (_____%) or _________
iii) Evidence of _________ or _________(____)

A

M-protein

≥10; Plasmacytoma

organ or tissue impairment (CRAB)

51
Q

Staging – SALMON-DURIE SS

Stage I
Hemoglobin level ___________

Calcium level _________

Radiograph showing __________

(Low or high?) M protein values

A

greater than 10 g/dL

less than 12 mg/dL

normal bones or solitary plasmacytoma

Low

52
Q

Staging – SALMON-DURIE SS

Stage II
Findings that _____________________

A

fit neither stage I nor stage III criteria

53
Q

Staging – SALMON-DURIE SS

Stage III
Hemoglobin level _____________

Calcium level _________

Radiograph showing _________

(Low or high?) M protein value

A

less than 8.5 g/dL

greater than 12 mg/dL

advanced lytic bone disease

High

54
Q

Staging - ISS (International Staging System)

Stage I:
serum β2-microglobulin ___ mg/L
serum albumin ____ g/dL

Stage II: __________

Stage III: serum β2-microglobulin ______ mg/L

A

<3.5; >3.5

neither stage I or III.

≥ 5.5

55
Q

Management (cont’d) - #PRB- CAI !

A) Pain

i) Analgesic (____,_____)
ii) Local _______
iii)__________ for severe back

A

NSAID; opiates

radiotherapy

Spinal support corset

56
Q

Management (cont’d) - #PRB- CAI !

B) Renal failure

i) Rehydrate and treat underlying causes e.g hypercalcaemia, hyperuricaemia
ii) Pt needs to drink at least ____ of fluid/day.

A

3L

57
Q

Management (cont’d) - #PRB- CAI !

E) Anaemia
i) __________

ii) Red cell ______

A

Erythropoietin

transfusion

58
Q

Management (cont’d) - #PRB- CAI !

Bone disease/hypercalcaemia
i)__________ eg. ______

A

Biosphophonates

Pamidronate

59
Q

Management (cont’d) - #PRB- CAI !

Compression Paraplegia
i)__________
Ii) ________ ————

A

Irradiation

Decompression Laminectomy

60
Q

Management (cont’d) - #PRB- CAI !

Infections
i)_______ antibiotics, antiviral agents and _________ concentrates infusion.

A

Broad spectrum

Immunoglobulin

House Hemat (29 decks)

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