multiple myeloma

Question 1

Multiple myeloma definition

Answer 1

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

Question 2

Features of MM

Answer 2

clonally rearranged immunoglobulin and usually secrete a monoclonal immunoglobulin

Question 3

CRAB features of MM

Answer 3

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

Question 4

Myeloma defining events

Answer 4

• 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

Question 5

2nd most frequent hematological dx

Answer 5

Multiple myeloma

Question 6

1% of cancers caused by

Answer 6

Multiple myeloma

Question 7

Multiple myeloma account for these percent of hematological dx

Answer 7

10-13%

Question 8

Age disease affects

Answer 8

Older people

70yrs median age

Question 9

Asymptomatic phase in MM

Answer 9

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

Question 10

Asymptomatic or smouldering myeloma

Answer 10

Similar laboratory MM but no organ damage showing clinical features

Question 11

MGUS

Answer 11

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

Question 12

Percentage of cases becoming symptomatic

Answer 12

10%

Question 13

Aetiology of MM

Answer 13

Largely unknown

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

Question 14

Phenotype of malignant plasma cell

Answer 14

HIGH CD-38
HIGH CD138
LOW CD45

Question 15

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

Answer 15

Secretion of interleukins

Question 16

Hyperviscosity syndrome

Answer 16

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

Usually IgA and IgM caused

Question 17

Severity of hyperviscosity depends on

Answer 17

immunoglobulin being cloned

the higher immunoglobulin size the higher the hyperviscosity

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

Question 18

Why is there reduction in immunity in a person with MM

Answer 18

there is reduced production of normal immunoglobulin

Question 19

Hallmarks of MM

Answer 19

Bone dx

Question 20

What happens in bone dx

Answer 20

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

Question 21

Cytogenic changes in MM

Answer 21

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

Question 22

Clinal features

Answer 22

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

Question 23

What causes thrombosis in MM

Answer 23

High factor 8
Acquired protein C resistance
Hypofibrinolysis
Immune modulatory drugs

Question 24

Immune modulatory drugs include

Answer 24

Ledalidomide

Thallidomide

Question 25

What causes bleeding in MM

Answer 25

Non functional platelets- proteins coat surface of platelets interference with fibrin polymerization Thrombocytopenia from bone marrow suppression

Question 26

How to diagnose MM

Answer 26

``` 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 ```

Question 27

Investigations in people with suspected MM

Answer 27

``` 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 ```

Question 28

Bad prognosis markers

Answer 28

``` 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 ```

Question 28

International staging system

Answer 28

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

Question 29

Supportive treatment

Answer 29

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

Question 30

Primary induction transplant therapy

Answer 30

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

Question 31

Relapse treated with

Answer 31

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

Question 32

Mean survival from diagnosis in MM

Answer 32

4-5 YRS

Question 33

Differential diagnosis of MM

Answer 33

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

Question 34

What is amyloidosis

Answer 34

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

Question 35

Amyloid staining

Answer 35

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

Question 36

Types of amyloidosis

Answer 36

AL AA Familial amyloid

Question 37

Classical features of AL

Answer 37

``` macroglossia carpall tunnel syndrome peripheral neuropathy purpura malabsorption nephrotic syndrome cardiomyopathy ```

Question 38

Waldestroms macroglobineamia characterised by

Answer 38

prescence of paraprotein IGM Provides symptoms of tissue infiltration, hyperviscosity of blood,

Question 39

Osteolytic lesions rare in

Answer 39

Waldestroms macroglobulineamia