Multiple Myeloma 101: Understanding Your Labs Tim Wassenaar MD MS Hematologist, Director of Clinical Trials UW Cancer Center at ProHealth Care
None Disclosures
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 Plasma Cell Monocytes eat bacteria and other unwanted things regulate immune system
Red Blood Cells (Erythrocytes) Biconcave discs top side Little bags of hemoglobin Function: carry 0 2 to tissues, CO 2 to lungs
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
Google, 2009 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
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