Multiple Myeloma Flashcards by Iseoluwa Ojo

Paraprotein

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

a single clone

monoclonal; M

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

paraproteinaemia

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Paraprotein

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

clonal transformation

Retain

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“M” in M protein for ________

monoclonal

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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

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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

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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

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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

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Malignant monoclonal gammopathies

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

Multiple myeloma

Smoldering multiple myeloma

Plasma cell

Nonsecretory

Osteosclerotic; POEMS

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Malignant monoclonal gammopathies

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

IgG, IgA, IgD, IgE and free light chain

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Plasmacytoma
i) _______ plasmacytoma of _____/ __________ plasmacytoma

Solitary; bone

extramedullary

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MGUS

The following criteria must be met:

Serum monoclonal protein: ___ g/dL

Clonal bone marrow plasma cells: ____ %

(Presence or Absence?) of end-organ damage

<10

Absence

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end-organ damage such as

_______
_________
__________
___________(CRAB)

hypercalcemia, renal insufficiency, anemia, and bone lesions

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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

Absence

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Smoldering multiple myeloma is also referred to as ___________ multiple myeloma

asymptomatic

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In Smoldering multiple myeloma

Serum monoclonal protein is usually Ig__ or Ig___

G or A

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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.

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_______ is the most common and important monoclonal gammopathy

Multiple myeloma

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Multiple myeloma

usually presents as ______ throughout the ______ system.

multiple tumour masses

skeletal

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Epidemiology of multiple myeloma

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

10; 1

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Epidemiology of multiple myeloma

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

Median age at diagnosis is ____ years.

Higher

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Epidemiology of multiple myeloma

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

male

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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

Male

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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)

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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.

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