Having a full and accurate diagnosis is important so that we can personalize a treatment plan for you. We use a comprehensive array of standard and specialized tests to help us understand the characteristics and extent of your specific disease.

Diagnostic testing may include:

• Blood work
  • Complete blood count (CBC) measures the levels of red cells, white cells, and platelets in your blood. If there are too many myeloma cells in your bone marrow, some of these blood cell levels will be low. We often find that patients have a low red blood cell count, which results in anemia (due to a reduced amount of hemoglobin, the protein that carries oxygen).
  • Serum protein electrophoresis (SPEP) measures normal and abnormal proteins in plasma cells. Myeloma cells produce an abnormal protein (also known as a monoclonal immunoglobulin or M protein). If we find this abnormal protein, it might indicate that you have myeloma.
  • Serum immunofixation electrophoresis (IFE) identifies the subtype of abnormal protein, or M protein, in your plasma cells.
  • Serum quantitative immunoglobulins (Igs) measure the levels of heavy protein chains (including IgA, IgD, IgE, IgG, and IgM) in the abnormal antibodies that are overproduced by myeloma cells. These levels may not always be elevated.
  • Serum free light chain assay measures the levels of antibody light chains, classified as kappa or lambda, made by myeloma cells. Abnormal levels suggest that you might have multiple myeloma.
  • Chemistry profile measures the levels of certain substances, such as calcium, albumin, lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and creatinine. If you have abnormal levels of creatinine, for instance, we can tell that there might be kidney involvement in your myeloma.
• Twenty-four-hour urine test involves the collection of urine over a 24-hour period to measure the amounts of proteins in the urine. Sometimes kidneys excrete pieces of M protein into the urine. This urine protein, known as Bence Jones protein, is an indicator of myeloma.
• Magnetic resonance imaging (MRI) with diffusion-weighted whole body imaging (DWIBS) is a very sensitive imaging technique using strong magnets, radio waves, and a computer to make a series of detailed images that can identify areas of active myeloma in the bone. These active areas are referred to as bone lesions—they look like holes in the bones and have a Swiss cheese-like appearance. DWIBS is an advanced variation of MRI imaging that uses the diffusion of water molecules to generate contrast in MRI images. This helps provide further information about changes in tissues and lesions throughout your skeleton.
• Skeletal survey is a series of X-rays of bones in the body, usually including the skull, spine, pelvis, ribs, and long bones of the arms and legs. These images can reveal bone damage caused by myeloma.
• Positron emission tomography and computed tomography (PET/CT) scans are advanced nuclear imaging techniques that provide information about both the structure and function of cells and tissues. PET/CT scans help us assess changes in the bone structure as well as the number and size of bone lesions.
• Bone marrow aspiration and biopsies involve removing some of your bone marrow and blood and a small piece of bone by inserting a special biopsy needle into your hip bone. Our pathologists look at the biopsy tissue under a microscope and use stains to identify abnormal cells. We make sure to capture enough tissue to perform advanced testing that helps us identify the unique characteristics of your disease.

Advanced testing and in-depth analyses of bone marrow aspirates and biopsies include:

• Cytogenetics involves studying the chromosomes, the parts of cells that contain genetic information. Some myeloma cells may have too many chromosomes (hyperdiploidy). Others may have abnormal chromosomes such as translocations (part of one chromosome has broken off and become attached to another chromosome) or deletions (part or all of a chromosome is missing). Information from cytogenetic studies helps us design an appropriate treatment plan for you.
• Fluorescence in situ hybridization (FISH) is similar to cytogenetic testing. It uses special dyes that attach only to specific parts of chromosomes, allowing us to identify changes that are too small to be detected with regular cytogenetic testing.
• DNA sequencing uses advanced technology tools such as next-generation sequencing to analyze DNA from your myeloma cells for gene mutations. This information can help us tailor treatment for you.
• Risk profiling includes a variety of tests that we perform on your bone marrow biopsy sample to identify the molecular features of your disease. This information helps us determine how you might respond to specific treatments and which treatments are likely to be the most effective for you.
• Minimal Residual Disease: Utilizing either Next-generation Flow Cytometry (NGF) or Next-generation Sequencing (NGS) to evaluate low levels of disease (cancer cells in the bone marrow) on the order of 1 cell in 1 to 10 million. This information can be used to help guide treatment decisions as well as to provide prognostic information.

Multiple Myeloma Staging

Following diagnosis, your doctor will determine the extent of your myeloma and evaluate which multiple myeloma treatment option is best suited for you. This process is called staging. There are different staging systems that we use to characterize multiple myeloma.

Durie-Salmon Staging: The Durie-Salmon Staging involves three stages of myeloma: Stage I, Stage II, and Stage III that correspond to low, intermediate and high malignant plasma cell masses, respectively. This staging system incorporates four important factors that correlate with tumor mass:

• Levels of monoclonal protein in the blood or urine: Large amount of monoclonal protein in the blood may indicate the presence of a large number of malignant plasma cells.
• Calcium level in the blood: Hypercalcemia or higher than normal level of calcium in the blood may indicate significant bone damage.
• Extent and severity of bone damage: Imaging tests are performed to identify the location and extent of bone damage and reveal how advanced the multiple myeloma is.
• Hemoglobin level in the blood: Low level of hemoglobin or anemia may mean high level of multiple myeloma cells.

International Staging System (ISS): The ISS incorporates data on the levels of serum β2 microglobulin and serum albumin, and provides the most powerful, reproducible 3-stage classification. High serum β2 microglobulin levels indicate high tumor mass and reduced renal function, and low serum albumin levels is caused by inflammatory cytokines like interleukin-6 produced by the myeloma microenvironment.

• Stage I: serum β2 microglobulin < 3.5 mg/L and serum albumin ≤ 3.5 g/dL
• Stage II: neither Stage I nor Stage III
• Stage III: serum β2 microglobulin ≥ 5.5 mg/L

Revised International Staging System (R-ISS): The R-ISS combines factors from the ISS (serum β2 microglobulin and serum albumin), with chromosomal abnormalities detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH).  The risk stratification involves 3 stages:

• Stage I: ISS Stage I, standard risk chromosomal abnormalities, normal LDH
• Stage II: neither Stage I nor Stage III
• Stage III: ISS Stage III, and either high-risk chromosomal abnormalities* or high LDH

* Presence of chromosomal deletion (17p) and/or chromosomal translocation t(4;14) and/or chromosomal translocation t(14;16).

At the Center of Excellence for Multiple Myeloma we use these staging systems to characterize your disease and help determine the most appropriate treatment regimen.