Multiple Myeloma Flashcards
What is multiple myeloma
DisseminatedDisease due to malignant transformation of differentiated B cells
Usually secrete monoclonal immunoglobulin
Crab features of multiple myeloma
C- hypercalcemia
R- renal impairment
A- anemia
B- bone disease
What is monoclonal gammopathy in multiple myeloma
Peak in only one type of antibody
Percentage of clonal plasma cells on bone marrow examination in multiple myeLoma
60% or more
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
Second most present hematological disease
Multiple myeLoma
Percentage of multiple myeloma in all cancer
One percent
What is plasmacytoma
Collection of plasma cells anywhere in the body
Percentage of multiple myeLoma in hematological malignancies
10 to 13 %
People at risk of multiple myeLoma
Old people around 70 years
2/3 more than 65yo when diagnosed
What is monoclonal gammopathy of undetermined significance ( MGUS)
Prolonged asymptomatic phase that may last for years where there is monoclonal gammopathy
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
Percentage of chance that an asymptomatic myeloma becomes multiple myeloma
10%
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
What is the phenotype of malignant plasma cell
High CD38
High CD138
Low cD45
Why is there hyperviscosity syndrome in multiple myeloma
increased protein content and large molecular size, abnormal polymerization, and abnormal shape of immunoglobulin molecules.
Presentation of hyperviscosity syndrome
Confusion
disorientation
What determines the severity of Hyperviscosity syndrome inmultiple myeLoma
If it’s a IgA ( dimer) or IgM( pentamer )because they have the biggest size
Why is there a reduced immunity in multiple myeloma
Reduce the production of normal immunoglobulin
What disease is a hallmark of multiple myeloma
Bone disease
Why is there bone disease such as osteolysis in multiple myeLoma
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
Osteoporosis -> Lytic lesions -> Pathological fractures
What are the cytogenetic changes in multiple myeloma
Multiple structural chromosome changes
13q loss Hyperdiploidy Hypodiploidy Chrom 8, 13,14, loss Del(17p)
Presentation of multiple myeloma
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
