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Haematology > multiple myeloma > Flashcards

multiple myeloma Flashcards

1
Q

Multiple myeloma definition

A

disseminated dx arising from malignant transformation of a terminally differentiated B cell

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2
Q

Features of MM

A

clonally rearranged immunoglobulin and usually secrete a monoclonal immunoglobulin

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3
Q

CRAB features of MM

A

C- hypercalcemia due to increased osteoclast activity
R- Renal dx
A- Anemia
B- Bone dx

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4
Q

Myeloma defining events

A
  • 60% or more clonal plasma cells in bone marrow
  • More than 1 focal lesion on MRI that is at least 5mm or greater in size
  • Provided Involved free light chain at least 100mg/L, serum involved/ Uninvolved free light chain ratio should be 100 or greater
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5
Q

2nd most frequent hematological dx

A

Multiple myeloma

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6
Q

1% of cancers caused by

A

Multiple myeloma

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7
Q

Multiple myeloma account for these percent of hematological dx

A

10-13%

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8
Q

Age disease affects

A

Older people

70yrs median age

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9
Q

Asymptomatic phase in MM

A

May last for years undetected and can only be detected by MGUS

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10
Q

Asymptomatic or smouldering myeloma

A

Similar laboratory MM but no organ damage showing clinical features

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11
Q

MGUS

A

There is a peak of one particular immunoglobulin because that antibody is being clonally produced

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12
Q

Percentage of cases becoming symptomatic

A

10%

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13
Q

Aetiology of MM

A

Largely unknown

But myeloma cell has undergone immunoglobulin gene recombination, class switching, somatic hypermutation

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14
Q

Phenotype of malignant plasma cell

A

HIGH CD-38
HIGH CD138
LOW CD45

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15
Q

Overexpression of adhesion molecules on plasma cell clone, extracellular matrix proteins etc lead to

A

Secretion of interleukins

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16
Q

Hyperviscosity syndrome

A

iNCREASED immunoglobulin produced makes blood ver viscous. It produces CNS disturbances

Usually IgA and IgM caused

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17
Q

Severity of hyperviscosity depends on

A

immunoglobulin being cloned

the higher immunoglobulin size the higher the hyperviscosity

IGG- MONOMER
IGA- DIMER
IGM- PENTAMER..WILL BE WORSE

18
Q

Why is there reduction in immunity in a person with MM

A

there is reduced production of normal immunoglobulin

19
Q

Hallmarks of MM

A

Bone dx

20
Q

What happens in bone dx

A

MM cells adhere to stromal cells induces osteoclast activating factors TNF alpha, IL-6,IL-1,RANK-L,VEGF, MIP alpha,etc

When RANK-L is increased, it promotes bone depletion, by stimylating osteoclast action

21
Q

Cytogenic changes in MM

A 
13q loss
Hyperdiploidy
Hypodiploidy
loss of chromosome 8,13,14
Deletion at chromosome 17p
22
Q

Clinal features

A

Skeletal

Marrow infiltration and marrow faluire

Infection due to decreased immunity

Renal failure usually due to obstruction by proteinaceous casts, hypercalcemia, infection, uric acid, amyloidosis

Symptoms of hyperviscosity

23
Q

What causes thrombosis in MM

A

High factor 8
Acquired protein C resistance
Hypofibrinolysis
Immune modulatory drugs

24
Q

Immune modulatory drugs include

A

Ledalidomide

Thallidomide

25
Q

What causes bleeding in MM

A

Non functional platelets- proteins coat surface of platelets

interference with fibrin polymerization

Thrombocytopenia from bone marrow suppression

26
Q

How to diagnose MM

A 
FBC- ROULEAUX FORMATION, leucoerythroblastosis
Increased ESR
Plasma cells greater than 10% in bone marrow
Paraprotein in serum
Bence jones protein in urine
normal IgG and albumin reduced
Serum B2 macroglobulin increased
C reactive protein increased
Skeletal survey
Myeloma related organ damage due to CRAB
27
Q

Investigations in people with suspected MM

A 
Serum and urine assessment for monoclonal protein
Serum free light chain
Bone marrow aspiration
Serum beta 2 macroglobulin
ALbumin
serum imunoglobulins
lactate dehydrogenase
Fluorescent in situ hybridization
MRI
POSITRON EMMISSION TOMOGRAPHY
Low dose whole body CT scan
28
Q

Bad prognosis markers

A 
Age greater than 65
Poor performance status
Hb less than 8.5
Hypercalcemia
Advanced lytic bone lesions
Abnormal renal fxn
Serum albumin < 30g/dl
B2 macroglobulin> 6mg/l
High C reactive protein
high serum LDH
High paraprotein
cytogenetics t(4,14), del(17p), t(14,16)
Hypodiploidy
28
Q

International staging system

A

Stage 1- beta 2 microglobulin 3.5 and below and albumin 3.5 and greater

Stage 2- B2M less than 3.5 AND ALBUMIN less than 3.5G/DL
or greater than 3.5 and less than 5.5

Stage 3- B2M 5.5 and greater

29
Q

Supportive treatment

A 
Calcium- hydration, steroids
lytic lesions -- bisphosphonates, radiotherapy
Radiotherapy for pain and fracture
Uric acid allopurinol
Renal failure- hydration,steroids
30
Q

Primary induction transplant therapy

A

Bortezomib/dexamethasone
Bortezomib/doxorubicin/dexamethasone
Bortezomib,/thallidomide/dexamethasone
Lenalidomide/ dexamethasone

31
Q

Relapse treated with

A

Agents not previously used
Bortezomib/cyclophosphamide/dexamethasone
Carfilzomib
Thalidomide
Lenalidomide/cyclophosphamide/dexamethasone
Pamalidomide

32
Q

Mean survival from diagnosis in MM

A

4-5 YRS

33
Q

Differential diagnosis of MM

A

Monoclonal gammopathy of undetermined significance, no evidence of B cell disorder, M protein less than 30g/l, marrow plasma cells less than 10%

Smouldering multiple myeloma; no organ damage

Plasmacytoma

Amyloidosis

Waldestroms macroglobulinemia- IgM mediated

Heavy chain dx

34
Q

What is amyloidosis

A

Disorder of protein folding where normally soluble protein are deposited as beta pleated sheets and deposited in organs leading to organ failure

35
Q

Amyloid staining

A

Stains positive with congo red. and demonstrated in rectal, renal biopsies

36
Q

Types of amyloidosis

A

AL
AA
Familial amyloid

37
Q

Classical features of AL

A 
macroglossia
carpall tunnel syndrome
peripheral neuropathy
purpura
malabsorption
nephrotic syndrome
cardiomyopathy
38
Q

Waldestroms macroglobineamia characterised by

A

prescence of paraprotein IGM

Provides symptoms of tissue infiltration, hyperviscosity of blood,

39
Q

Osteolytic lesions rare in

A

Waldestroms macroglobulineamia

Haematology (29 decks)

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