Multiple Myeloma Flashcards
Paraprotein
Immunoglobulin produced from ____________ of plasma cells( _______ antibody or ___ protein ) is called a paraprotein.
a single clone
monoclonal; M
When a paraprotein is present in plasma in excessive amount, it is referred to as _______________.
paraproteinaemia
Paraprotein
Paraproteinaemias are usually as a result of ___________ of ____-cells which (lose or retain ?) their ability to mature into plasma cells.
clonal transformation
B
Retain
“M” in M protein for ________
monoclonal
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.
Hetero
monoclonal Immunoglobulin
its fragments
Paraproteinemias may be categorized according to the type of monoclonal protein found in blood:
1. _______ only (or _________).
- ________ only
- _________
Light chains ; Bence Jones protein
Heavy chains
Whole immunoglobulins
Paraproteinaemias
- Light chains only : This may be associated with __________ or _________
- Heavy chains only (also known as “ _____________ “)
- Whole immunoglobulins- “__________ “.
multiple myeloma ; AL amyloidosis
heavy chain disease
M-protein
Classification of Paraproteinaemias
Mnemonic = __________
Now , list them
MP MoW HP
Malignant monoclonal gammopathies
Plasmacytoma
Monoclonal gammopathy of undetermined significance
Waldenstrom’s macroglobulinemia
Heavy chain disease
Primary amyloid
Malignant monoclonal gammopathies
i)___________
ii)_____________
iii) _______ leukaemia
iv)_______ myeloma
v)__________ myeloma (_____ Syndrome)
Multiple myeloma
Smoldering multiple myeloma
Plasma cell
Nonsecretory
Osteosclerotic; POEMS
Malignant monoclonal gammopathies
Multiple myeloma (____,____,_____,_____, and _________)
IgG, IgA, IgD, IgE and free light chain
Plasmacytoma
i) _______ plasmacytoma of _____/ __________ plasmacytoma
Solitary; bone
extramedullary
MGUS
The following criteria must be met:
Serum monoclonal protein: ___ g/dL
Clonal bone marrow plasma cells: ____ %
(Presence or Absence?) of end-organ damage
<3
<10
Absence
end-organ damage such as
_______
_________
__________
___________(CRAB)
hypercalcemia, renal insufficiency, anemia, and bone lesions
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
3
10
Absence
Smoldering multiple myeloma is also referred to as ___________ multiple myeloma
asymptomatic
In Smoldering multiple myeloma
Serum monoclonal protein is usually Ig__ or Ig___
G or A
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 ________
clonal proliferation
malignant
bone marrow
monoclonal protein
organ dysfunction.
_______ is the most common and important monoclonal gammopathy
Multiple myeloma
Multiple myeloma
usually presents as ______ throughout the ______ system.
multiple tumour masses
skeletal
Epidemiology of multiple myeloma
It accounts for ____% of all haematological malignacies and ___% of all cancers.
10; 1
Epidemiology of multiple myeloma
The incidence is (lower or higher?) among blacks.
Median age at diagnosis is ____ years.
Higher
67
Epidemiology of multiple myeloma
There is a slight (male or female?) predominance.
male
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.
10; 1
Higher
67
Male
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)_____________
Occupational
Environmental
Chronic antigenic
Genetic
Monoclonal Gammopathies of Undetermined Significance (MGUS)
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).
Low -grade radiation
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).
repeated infections, allergic conditions, autoimmune diseases
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).
Okay?🌚🌚
Pathogenesis
Three (3) primary processes lead to the complex disruption of organs in multiple myeloma:
_______________ in Bone marrow
__________ of monoclonal immunoglobulin
_________ of _________
Plasma cell expansion
Overproduction
Overproduction of various cytokines
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 ___________________
gradually replaced by the slowly expanding malignant clone.
Decr; pancytopenia
bone surface “cortex” destruction.
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.
Chronic B-cell Ag stimulation
apoptosis; M- protein
intact immunoglobulin
IgG, IgA ; IgD and IgE
light chains kappa or lambda.
amyloid deposits
Note, in multiple myeloma
Free light chains pass through the ________, accumulate in the kidney parenchyma resulting in _________
glomerular basement membrane
renal dysfunction.
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 _____
osteoclasts
IL-1, TNF, IL-6, macrophage
inflammatory protein (MIP).
RANKL; OPG
RANKL , receptor activation of __________ ligand
OPG (__________ ), a _______ of __________
NF-kappabeta
osteoprotegerin
natural antagonist of RANKL
Pathogenesis of multiple myeloma: Overproduction of various cytokines
Overexpression of RANKL is associated with increased generation of ______ from _________
This leads to _______ ( _______,_________, and _____________).
osteoclast
monocyte precursors.
bone destruction
lytic bone lesions, pathological fractures and osteoporosis
Clinical features of multiple myeloma -
#BARR !
1)_____ pain (especially ______)
2)______ features
3)_____ failure
4) Recurrent ______
Bone; back ache
Anemia
Renal
infections
Clinical features of multiple myeloma -
#BARR !
1) Bone pain (especially back ache) resulting from _________ and ________
2) Anemia features include _____,_____,_____, and ______
pathological fractures and vertebral collapse.
fatigue, pallor, palpitations and shortness of breath.
Clinical features of multiple myeloma -
#BARR !
Renal failure
causes:
i)_______
ii) ________ deposition (_______ protein) in renal tubules
iii) _______
iv) renal infections
v) Metastatic disease to ______
hypercalcemia
light chain ; Bence jones
amyloidosis
interstitium
Clinical features of multiple myeloma -
#BARR !
Recurrent infections
causes: i) ______ , ii) suppressed ________ immunity due to ____________________[
neutropenia
humoral
low production of normal immunoglobulins
Clinical features of multiple myeloma (Cont’d)- #BNAHH
Bleeding
causes:_______, abnormal _____ function, abnormal coagulation -the paraprotein _________ and _________ and interferes with their functions.
thrombocytopenia
platelet
covers the platelets’ surface
absorbs the clothing factors
Clinical features of multiple myeloma (Cont’d)- #BNAHH!
Hyperviscosity syndrome (especially in Ig__ MM): _____,______,______, and _____
Hypercalcemia: _____, headache, ____uria, weakness, coma
A
headache, blurred vision, bleeding and coma.
thirst
poly
Clinical features of multiple myeloma (Cont’d)- #BNAHH!
Neurological symptoms: peripheral _______, vertebral ______, and spinal cord ________.
Amyloidosis: (common or rare?) complication
polyneuropathies
fracture; compression
Rare
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 _________
Anemia, leukopaenia and thrombocytopenia
normo; normo
rouleaux
increased immunoglobulin.
Laboratory findings - #HBR ! A) Haematology
ESR: ____eased because of _________
Bone marrow aspiration and biopsy: shows ____eased plasma cells and tissue _________.
incr; high immunoglobulin level.
incr
plasmacytoma
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).
Immunofixation and Immunoelectrophoresis
Laboratory findings - #HBR !
Abnormal renal function - serum ______ increase, _____ and _____ often increase.
creatinine; uric acid and urea
Laboratory findings - #HBR !
Serum __________ globulin increase.
Serum calcium ____ease and Proteinuria.
β-2 micro
incr
Laboratory findings - #HBR !
Urine studies:______ urine collection for Bence Jones proteinuria.
24 Hours
Laboratory findings of multiple myeloma - #HBR !
Radiological examination
i) Skeletal survey in the ____ skeleton for _________ or __________ using MRI, CT-scan and PET-scan.
axial
osteolytic bone lesions
punched-out lytic lesions
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 ______
≥ 11.5
> 2; > 153
<10
lytic bone lesions
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 _________(____)
M-protein
≥10; Plasmacytoma
organ or tissue impairment (CRAB)
Staging – SALMON-DURIE SS
Stage I
Hemoglobin level ___________
Calcium level _________
Radiograph showing __________
(Low or high?) M protein values
greater than 10 g/dL
less than 12 mg/dL
normal bones or solitary plasmacytoma
Low
Staging – SALMON-DURIE SS
Stage II
Findings that _____________________
fit neither stage I nor stage III criteria
Staging – SALMON-DURIE SS
Stage III
Hemoglobin level _____________
Calcium level _________
Radiograph showing _________
(Low or high?) M protein value
less than 8.5 g/dL
greater than 12 mg/dL
advanced lytic bone disease
High
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
<3.5; >3.5
neither stage I or III.
≥ 5.5
Management (cont’d) - #PRB- CAI !
A) Pain
i) Analgesic (____,_____)
ii) Local _______
iii)__________ for severe back
NSAID; opiates
radiotherapy
Spinal support corset
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.
3L
Management (cont’d) - #PRB- CAI !
E) Anaemia
i) __________
ii) Red cell ______
Erythropoietin
transfusion
Management (cont’d) - #PRB- CAI !
Bone disease/hypercalcaemia
i)__________ eg. ______
Biosphophonates
Pamidronate
Management (cont’d) - #PRB- CAI !
Compression Paraplegia
i)__________
Ii) ________ ————
Irradiation
Decompression Laminectomy
Management (cont’d) - #PRB- CAI !
Infections
i)_______ antibiotics, antiviral agents and _________ concentrates infusion.
Broad spectrum
Immunoglobulin
