Upload
others
View
7
Download
0
Embed Size (px)
Citation preview
Multiple Myeloma 101: Understanding Your Labs
Tim Wassenaar MD MS Hematologist, Director of Clinical Trials
UW Cancer Center at ProHealth Care
Disclosures
• None
Outline
• Define hematopoiesis
– WBCs, RBCs, platelets
• What is multiple myeloma?
• How do we diagnose myeloma?
Outline
• Laboratory studies – Monoclonal protein – Immunoglobulins, beta 2 microglobulin – Bone marrow biopsy
• Laboratory results in the setting of multiple myeloma – CRAB – Free light chains
• Conclusions
Hematopoiesis
• Websters defines as:
– “the formation of blood or of blood cells in the living body.”
• Where are blood cells made?
Bone Marrow
Williams, 2009
White Blood Cells (Leukocytes)
• Neutrophils – eat bacteria – produce inflammatory molecules
• Lymphocytes
– make antibodies – kill foreign or infected cells – regulate immune system
• Monocytes
– eat bacteria and other unwanted things – regulate immune system
Plasma Cell
Red Blood Cells (Erythrocytes)
• Biconcave discs
• Little bags of hemoglobin
• Function: carry 02 to tissues, CO2 to lungs
top side
Platelets
• Smallest formed elements in blood
• Not really cells (no nuclei) but fragments of large cells called megakaryocytes found mainly in bone marrow
• Function: help blood clot, prevent bleeding
How do we diagnose multiple myeloma?
• Laboratory evaluation – Complete blood count – Protein studies (serum, urine) – Serum immunoglobulins (IgG, IgM, IgA) – Kidney function, chemistries, calcium, albumin
• Radiographic evaluation
– Xrays (skeletal survey) – CT, MRI, PET scan also used in certain circumstances
• Pathologic evaluation
– Bone marrow biopsy
Laboratory Studies
• Monoclonal protein – 97% of patients will have a protein in the blood or
urine • 80% of time protein is seen by SPEP
• Up to 93% of time if immunofixation performed
• 97% if serum free light chains and urine protein studies are performed
– No detectable monoclonal protein (3%) • Non-secrectory myeloma
Monoclonal Protein
Uptodate, 2017
Laboratory Studies
• Monoclonal protein – IgG – 52 percent
– IgA – 21 percent
– Kappa or lambda light chain only (Bence Jones) – 16 percent
– IgD – 2 percent
– Biclonal – 2 percent
– IgM – 0.5 percent
– Negative – 6.5 percent
Uptodate, 2017
Laboratory Studies
• Free light chain – Measures kappa and lambda
immunoglobulin chains not bound to heavy chains • Normal is Kappa:Lambda ratio of
2:1
– Abnormal free light chain ratio
seen in 90% of patients with multiple myeloma
– Now considered a diagnostic criteria for multiple myeloma
Laboratory Studies
• Serum Immunoglobulins – Measurement of normal and abnormal protein
• IgG, IgM, IgA
– If no localized band seen on SPEP, 20% have hypogammaglobulinemia
– Reduction of normal uninvolved immunoglobulin levels common • 91% have one, 73% have both reduced
Laboratory Studies
• Beta 2 microglobulin
– Serum test
– Prognostic factor for multiple myeloma staging
– Elevated in 75% of patients at diagnosis
– Higher level represents:
• Greater tumor burden
• Can be associated with renal failure
Laboratory Studies
• Bone Marrow biopsy
– Key component to diagnosis of myeloma
– 3 main components:
• Morphology – # and appearance of plasma cells
• Immunophenotype – Monoclonal, kappa/lambda ratio
• Cytogenetics – Chromosome abnormalities of myeloma cells
Bone Marrow
Williams, 2009
Bone Marrow: Cytogenetics
• Chromosome abnormalities play a major role in development of multiple myeloma
• Detected by: – Karyotype (20-30% detection rate)
• Ploidy (Gain/trisomy, loss/hypodiploidy) • Deletion/monosomy
– Flourescent in situ hybridization (FISH)
• Play a major role in prognosis
Bone Marrow: Cytogenetics
Bone Marrow Cytogenetics
• No abnormality better than any – Detection of a clone reflects dividing cells
• High Risk – Hypodiploidy
• Intermediate Risk – Deletion 13
• Low Risk/Favorable – Hyperdiploidy
Bone Marrow: FISH
Blood 2002;99:3735
Bone Marrow Cytogenetics/FISH
Msmart guidelines, accessed 11/2017
Laboratory Studies: Clinical Presentation
• Calcium increased
• Renal dysfunction
• Anemia
• Bone lesions
CRAB: Hypercalcemia
• Increase in the level of calcium – Seen in approximately 30% at diagnosis
– Serum calcium > 11 mg/dL (15%)
• Causes – Bone destruction, loss of kidney function,
monoclonal protein
• Symptoms – Drowsiness, confusion, loss of appetite, nausea,
constipation, excessive urination
CRAB: Kidney damage/failure
• Kidneys don’t filter the blood as well – Usually acute and reversible if caught early – Creatinine above normal (0.9-1.2 mg/dL) in 50%, > 2.0 mg/dL in
20% of cases at presentation – Can be the presenting symptom of the disease
• Causes
– Monoclonal protein (ie cast nephropathy) – Hypercalcemia – Medications
• Symptoms – Drowsiness, loss of appetite, nausea, constipation, excessive
urination/ loss of urination’
CRAB: Anemia
• Decrease in red blood cells, lower hemoglobin and hematocrit – Hemoglobin ≤12 g/dL
– Present in 73% of patients at diagnosis (97% overall)
• Causes – Bone marrow replacement
– Kidney damage
– Dilution in the case of a large M-protein
• Symptoms – Fatigue, shortness of breath
CRAB: Bone Pain/Destruction
• Present 60% of the time at diagnosis
• Causes
– Plasma cell invasion of bone (plasmacytoma)
– Plasma cell induced bone destruction
• Symptoms • Back or chest pain most common, but
also in arms and legs – Pain worse with movement, goes
away with rest • Can cause loss of height • Spinal cord compression (weakness in
arm/leg, incontinence) (5% of patients)
Laboratory Studies: Immune system dysfunction
• Increased risk of infections
• Causes – Impaired lymphocyte function
– Impaired plasma cell function
– Hypogammaglobulinemia (too little normal protein)
– Other
Laboratory Studies: Hyperviscosity Syndrome
• Blood becomes “thick and sticky” and prone to clot – Proteins (typically IgM) secreted by plasma cells
• Symptoms
– Bleeding from nose/mouth, blurred vision, headache, slurred speech, confusion, and heart failure
• Treatment
– Remove proteins from blood
Google®, 2009
Myeloma Diagnosis Criteria
Uptodate, 2017
Conclusions
• Multiple myeloma is characterized by excess immunoglobulin protein production by plasma cells with: – Detection of abnormal protein in serum and urine
– Increased abnormal plasma cells in bone marrow
• > 10% plus CRAB or FLC ratio > 100, or greater than 60%
– Associated symptoms:
• Calcium elevated • Renal dysfunction • Anemia • Bone destruction/lesions
Conclusions
• Can cause other symptoms:
– Immune system dysfunction
– Hyperviscosity
• Prognosis determined by genetic/molecular testing
• Clinical symptoms/findings and genetic studies drive treatment decisions
Questions