Multiple Myeloma Flashcards by Katya Angoua

What is multiple myeloma

DisseminatedDisease due to malignant transformation of differentiated B cells
Usually secrete monoclonal immunoglobulin

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Crab features of multiple myeloma

C- hypercalcemia
R- renal impairment
A- anemia
B- bone disease

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What is monoclonal gammopathy in multiple myeloma

Peak in only one type of antibody

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Percentage of clonal plasma cells on bone marrow examination in multiple myeLoma

60% or more

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What are the defining events in multiple myeloma

60% or more Clonal plasma cell on bone marrow examination

Involved or uninvolved free light chain ratio of 100 or greater in serum
At least 100 mg/L of involved free light chain

More than one focal lesion on MRI at least 5 mm or greater

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Second most present hematological disease

Multiple myeLoma

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Percentage of multiple myeloma in all cancer

One percent

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What is plasmacytoma

Collection of plasma cells anywhere in the body

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Percentage of multiple myeLoma in hematological malignancies

10 to 13 %

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People at risk of multiple myeLoma

Old people around 70 years

2/3 more than 65yo when diagnosed

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What is monoclonal gammopathy of undetermined significance ( MGUS)

Prolonged asymptomatic phase that may last for years where there is monoclonal gammopathy

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When do you say that there is a symptomatic or smoldering myeloma

Same laboratory as multiple myeLoma (calcium, renal function , high plasma cells in bone marrow ..)

no organ or tissue damage with no clinical features

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Percentage of chance that an asymptomatic myeloma becomes multiple myeloma

10%

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Pathogenesis of multiple myeLoma

Class switching, somatic hyper mutation and Immunoglobulin gene recombination in plasma cell which becomes myeloma cell

Overexpression of adhesion molecule of adhesion molecule on plasma cell clone
Overexpression of Extracellular matrix proteins, matrix stromal cells, intercellular adhesion molecules, vascular cell adhesion molecules

It direction leading to secretion of interleukins

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What is the phenotype of malignant plasma cell

High CD38
High CD138
Low cD45

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Why is there hyperviscosity syndrome in multiple myeloma

increased protein content and large molecular size, abnormal polymerization, and abnormal shape of immunoglobulin molecules.

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Presentation of hyperviscosity syndrome

Confusion

disorientation

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What determines the severity of Hyperviscosity syndrome inmultiple myeLoma

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If it’s a IgA ( dimer) or IgM( pentamer )because they have the biggest size

Why is there a reduced immunity in multiple myeloma

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Reduce the production of normal immunoglobulin

What disease is a hallmark of multiple myeloma

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Bone disease

Why is there bone disease such as osteolysis in multiple myeLoma

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Osteoclast activity increase -> secretion of osteoclast activating factors (TNF-alpha, IL6, IL1, hepatocytes growth factors, parathyroid hormone, RANKL, VEGF ,MIP-1a)
memorize RANK-L and MIP-1a

Decreased osteoprotegerin OPG

Bone disease progression in multiple my Loma

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Osteoporosis -> Lytic lesions -> Pathological fractures

What are the cytogenetic changes in multiple myeloma

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Multiple structural chromosome changes

13q loss
Hyperdiploidy
Hypodiploidy
Chrom 8, 13,14, loss 
Del(17p)

Presentation of multiple myeloma

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Skeletal (bone pain, fractures , paraplegia ,quadriplegia)
marrow infiltration (Marrow failure anemia, neutropenia, thrombocytopenia)
infection
renal failure
Symptoms of hyper viscosity
Thrombosis
Bleeding

Why is there infection in multiple myeloma

Due to decreased normal immunoglobulin

Why is there a renal failure in multiple my Loma

Obstruction of distal renal tubules by proteinaceous casts -> atrophy, interstitial fibrosis Hypercalcemia infection uric acid amyloidosis

What are some prothrombotic abnormalities in multiple my Loma

High factor VIII Acquired activated protein C resistance HYPOfibrinolysis Immune modulatorY DRUGS like thalidomide and lenalidomide used to treat MM

Why is there a bleeding in multiple myeloma

Non-functional platelets interference with fibrin polymerization thrombocytopenia from bone suppression suppression

Diagnosis of MM

``` Full blood counts - thin film rouleaux, leucoerythroblastosis ESR increased Bone marrow > 10% plasma cells Paraprotein in serum Bence jones protein in urine Reduced normal IgG and albumin Serum B2 microglobulin increased C reactive protein increased Skeletal survey ```

What are the diagnostic criteria for MM

Paraprotein in serum and or urine Bone marrow clonal plasma cell/ plasmacytoma Tissue impairment or myeloma related organs with end organ damage - crab manifestation

Poor prognostic factors in MM

``` More than 65 years old Poor performance status HB < 8.5 G/DL Hypercalcemia Advanced lytic bone lesions Abnormal renal function Serum albumin < 30g/l B2 microglobulin > 6mg High C reactive protein ```

Staging of MM

``` Stage l • Beta-2 microglobulin < 3.5g/dL and albumin ≥3.5g/dL Stage Il • Beta-2 microglobulin <3.5g/dL Albumin <3.5 g/dL OR • Beta-2 microglobulin level ≥3.5 to <5.5 g/dL Stage Ill • Beta-2 microglobulin ≥5.5 g/dL ```

Supportive treatment of MM

``` Transfusion - anemia Analgesics - pain Allopurinol - Uric acid Hydration and steroids - serum calcium Biphosphonates , radiotherapy - lytic lesions Orthopedic surgery - fractures Hydration, steroids, treat infection - renal failure Antibiotics - infection Radiotherapy - pain , fractures ```

Drugs given in primary induction for therapy in transplant candidates

``` Bortezomib dexamethasone doxorubicin Thalidomide Lenalidomide ``` VAD - first line

Treatment used for relapse or refractory disease

``` Different agent than one used in first line Bortezomid Cyclophosphamide Dexamethasone Car fil zombi Thalidomide Lenalidomide Pomalidomide ```

Median survival from diagnosis in MM

4 to 5 years

What’s presentation shows the worst prognosis

Renal failure

Features of plasma cell

Eccentric nucleus Basophilic cytoplasm Perinuclear halo

Differential diagnosis of MM

Monoclonal gammopathy of undermine significance Smoldering multiple myeloma Plasmacytoma Amyloidosis Waldenstrom macroglobulinemia Heavy chain disease

What is Amyloidosis

Disorder of protein folding which were soluble but now are deposited as beta pleated sheet

Complication of Amyloidosis

Dysfunction and organ failure

Types of Amyloidosis

AL AA familial amyloid

Classical features of amyloidosis

Malabsorption Nephrotic syndrome Cardiomyopathy Macroglossia Carpal tunnel syndrome Peripheral neuropathy Purpura

What is waldenstrom macroglobulinaemia

Presence of paraprotein IgM leading to organ infiltration and hyper viscosity

Multiple Myeloma Flashcards

(44 cards)