Multiple Myeloma and Understanding your Labs Matthew Ware

Multiple Myeloma and Understanding your Labs Matthew Ware

Multiple Myeloma and Understanding your Labs Matthew Ware PA-C Hematology/Oncology, BMT Froedtert and the Medical College of Wisconsin Cancer Center Disclosures None

Objectives Understand basic labs Interpreting myeloma labs Imaging and its role Diagnosing myeloma Topics for Discussion What is myeloma

Hematopoiesis Monoclonal proteins and detection Cytogenetics CRAB Diagnosing Responses Myeloma What is Myeloma? Disorder of white blood cells

called plasma cells, which produce antibodies (immunoglobulins) -Antibody is part of your immune system's defense Hematopoiesis Hematopoiesis- formation of blood cells.

Restricted to the skull, vertebrae, pelvis, and metaphyseal areas of long bones in adults [Mac] White Blood Cells (Leukocytes) WBCs are involved in fighting infections and foreign invaders Two major categories

Agranulocytes Granulocytes WBCs- Agranulocytes No granules in their cytoplasm and one lobe nucleus. Also called mononuclear leukocytes Two types: Lymphocytes

Monocytes WBCs- Agranulocytes: Lymphocytes Lymphocytes include Natural killer (NK) cells- cytotoxic or lead to cell death T cells- adaptive cytotoxic function B cells- antibody driven adaptive immunity

These are plasma cells WBCs- Agranulocytes: Monocytes Monocyte is the largest type of leukocyte and can attack, eat foreign material and that presented to them by T cells

WBCs- Granulocytes Granules in their cytoplasm and differing shape of their nucleus also call polymorphonuclear leukocytes (PML or PMN) Three major categories Neutrophils are 40-70% of WBCs. Elevated with inflammation or infection and fight

infection Eosinophils fight parasites and can be elevated in allergic reactions Basophils seen in inflammatory responses, acute and chronic Red Blood Cells (Erythrocytes) and Platelets Hemoglobin (Hb or Hgb)is the iron-

containing oxygen-transport protein in the RBCs Oxygen and carbon dioxide exchange in the lungs and tissues Platelets- involved in clotting after a bleed.

Fragments from megakaryocytes Diagnosing Myeloma Lab results CBC and chemistry panel Protein evaluation (blood and urine) Immunoglobulin (antibodies) levels- IgG, IgA, IgM

Imaging Bone lesions: X-ray (bone survey), CT, MRI, PET Pathology Bone marrow biopsy and cytogenetics

Monoclonal Protein Present in majority of patients and 97% have a monoclonal or M protein Made by non-functioning plasma cell seen in serum and/or 24 hour urine. Termed paraprotein

Testing- serum protein electropheresis (SPEP) or urine protein electopheresis (UPEP) No detectable protein in 3% (non-secretory) Monoclonal Protein Immunofixation (IFE) identifies the heavy and

light chain components Protein elecrophoresis (PEP) quantifies the protein Immunoglobulin IMF, 2018

Monoclonal Protein IgG- 52% IgA- 21% Kappa or lambda chain only (Bence Jones)- 16% IgD- 2% Biclonal- 2% IgM- 0.5%

Negative- 6.5% Free Light Chains (FLC) Measures Kappa and Lambda not bound to heavy chains. Normal ratio Kappa:Lambda is 2:1 for intact proteins and 0.26 to 1.65 when measuring

those unbound to heavy chains in the blood Ratio over 100, there was a 70-80% chance of end organ damage in 2 years Serum Immunoglobulins IgG, IgA, IgM Reduction in uninvolved immunoglobulins 90% to have reduction in one 70% to have both reduced

Bone Marrow Biopsy Bone Marrow Biopsy Percentage of plasma cells- Normal range is 1-2% Morphology- mature, immature, atypical

Mature is better prognosis Can derive kappa/lambda ratio from here or serum Cytogenetics- Chromosomal abnormalities IMF, 2018

Bone Marrow- Cytogenetics Chromosome abnormalities Conventional karyotype is 20-30% -Number and appearance of chromosomes gains, loses of chromosomes or deletions. Seen in dividing cells (1-3% of the plasma cells)

G, 2018 Bone Marrow- FISH Fluorescent in situ hybridization (FISH)- Fluorescent labeled DNA sequences that find a complement on the plasma cells Detects changes regardless of plasma cells growth

Chromosome- Long (q) and short (p) arm make up a chromatid Bone Marrow- FISH IMF, 2018 Cytogenetics and FISH

Presenting Symptoms CRAB Calcium (elevated) Renal (kidney) Failure Anemia Bone Lesions CRAB Calcium (elevated)- Hypercalcemia

Results from bone break down Symptoms of nausea, constipation, poor appetite, confusion, thirst Seen in 28% of patients on presentation CRAB Renal (kidney) Failure or Dysfunction Creatinine is a waste product from normal muscle

breakdown, filtered by kidneys and excreted Increased by monoclonal proteins and high calcium Symptoms of confusion, weakness, nausea, fatigue, fluid retention, decreased urine output Elevated creatinine in 48% on presentation CRAB Anemia

Lower red blood cells (hemoglobin) Marrow replaced by cancer cells Present with fatigue, weakness, lightheadedness, slowed thinking Seen in 73% patients on diagnosis CRAB Bone Lesions

Pain, commonly seen in ribs and spinal cord Bone breakdown can lead to fractures (broken bones), which release calcium into the bloodstream (hypercalcemia) Compression fractures Seen in 58% on presentation Imaging

X-ray or bone survey CT MRI PET/CT PET/MRI X-ray or Bone (skeletal) survey Thinning of bone or lytic lesions (holes in

bone) and/or fractures Limitation: 30% or more of trabecular (cancellous or spongy) bone must be missing to be seen on x-ray and 50-75% from lumbar vertebra before visible Appearance may not change following therapy Not best for determining cause of pain Not sensitive for focal lesions in bone marrow

X-ray AC, 2018 CT (Computed [axial] Tomography) Cross sectional x-ray Detection in up to 25% of those with negative

x-ray Soft tissue masses seen compared to x-ray Quicker than x-ray Not as sensitive as MRI in detecting lesions outside bone marrow Contrast More expensive than x-ray CT

AC, 2018 MRI (Magnetic Resonance Imaging) Picks up bone marrow involvement Preferred for spinal cord assessment (compression) Osteoporosis vs vertebral fractures

52% had normal x-rays Limitations: expensive, time consuming, implants (metal), pacemakers, claustrophobia, contrast and kidney function 9 month lag time of active disease MRI AC, 2018

PET/CT (Positron Emission Tomography) Radiolabeled glucose, uptake taken by cancer cells (actively dividing), muscle and brain FDG- fluorodeoxyglucose Find a mass where there is no bone lesion Extramedullary disease (Non-secretory) Three or more lesions poorer OS and PFS

Expensive Inflammation Skull lesions missed due to FDG avidity of brain Medicare covers 1 PET scan May cover additional during relapse, non-secretory additional malignancy PET/CT

AC, 2018 PET/MRI Equivalent to superior than PET/CT Up to 80% reduction in radiation Comparable cost Newly diagnosed patients as first imaging

modality PET/MRI Additional Labs Beta-2 microglobulin- (B2M) is a protein on the cell surface of most cells. Shed into bloodstream. Commonly seen on B lymphocytes and tumor

Total protein- albumin and globulin. M-protein increases blood globulin Albumin- Most abundant protein in blood plasma LDH (Lactate dehydrogenase)- enzyme in almost every cell and involved in fueling cells. Seen when cells are rapidly dividing and dying

RISS (Revised International Staging System) Based on blood work Amount of albumin Beta-2 microglobulin LDH Cytogenetics (bone marrow) 3 stages RISS- Stages

Stage I Beta-2 microglobulin < 3.5 mg/L AND Albumin is 3.5 g/dL or greater AND standard cytogenetics AND normal LDH levels Stage II

Not stage I or III Stage III Beta-2 microglobulin > 5.4 mg/L AND high risk cytogenetics AND/OR LDH high (2 times upper limit of normal)

Diagnostic Criteria Responses IMWG, 2018

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