My Multiple Myeloma - Understanding Multiple Myeloma

Diagnosing Multiple Myeloma

When you received your diagnosis of multiple myeloma, it was based on a number of tests performed by your healthcare team. Each of the blood, urine, bone marrow, and imaging tests performed were used to confirm the presence of the disease and to determine its stage and other characteristics it may have.

Commonly used tests can be categorized by their type as either:

Laboratory tests, which are tests that are performed on a sample of blood, urine, or other substance from the body.
Bone tests (such as bone marrow aspirate, bone marrow biopsy, or imaging tests), which allow your healthcare providers to see what is happening inside your bones.

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A diagnosis of multiple myeloma is based on the presence of an increased number of plasma cells in the bone marrow and, in most cases, the presence of excess protein (M-protein) in the blood or urine.

Some blood tests that can aid in the diagnosis and management of multiple myeloma include:

Complete blood count (CBC) measures the red blood cells, white blood cells, and platelets in your blood. With multiple myeloma, the body creates malignant (cancerous) plasma cells in the bone marrow. This can lead to a decrease in the number of healthy blood cells. An abnormal CBC might have been the first sign that led your doctor to request tests to diagnose your multiple myeloma.
Chemistry profile measures the levels of various components, which include those that relate to how the kidneys are functioning, such as blood urea nitrogen (BUN) and creatinine. Elevated levels of BUN and creatinine may indicate decreased kidney function.
Serum electrophoresis (SPEP) measures the levels of various proteins in your blood. Measuring and tracking the levels of M-proteins in the blood helps to determine the progression of your disease and your response to treatment. Most multiple myeloma patients have an increase in M-protein, known as an "M-spike" or "para protein."
Serum immunofixation electrophoresis (IFE) is a blood test that enhances the results of the SPEP analysis. It is a more sensitive test that is used to confirm and further characterize the specific abnormal proteins that may be detected on the SPEP.
Serum quantitative immunoglobulins is a test used to assess the M-spike produced by myeloma tumor cells. It measures a specific type of immunoglobulin (or antibody). Myeloma tumors usually produce only a single type of this immunoglobulin: IgG or IgA (or, in rarer instances, IgD or IgE). Measuring the levels of immunoglobulins in the blood is therefore another way for your healthcare providers to monitor your multiple myeloma.
Urine tests, such as 24-hour urine total protein and creatinine clearance, measure kidney function.
Serum free light chain assay detects and measures substances called free light chains (kappa and lambda). It is a sensitive indicator that helps to predict the progression or development of multiple myeloma.
Cytogenetics testing looks at the number, shape and arrangement of chromosomes present in a cell. Chromosomes are the genetic material contained in a cell (also referred to as deoxyribonucleic acid or DNA). This test is done to determine if any of the chromosomes are missing, expanded, or have been moved from their usual spot.

Some bone tests used for diagnosis include:

X-rays and other imaging tests, such as magnetic resonance imaging (MRI) and computed tomography (CT) scans, help identify any changes in bone structure and determine the number and sizes of any bony lesions (lytic lesions).
Bone Marrow Aspiration or Bone Marrow Biopsy detects an increase in the number of plasma cells in the bone marrow. An aspiration requires a sample of liquid bone marrow tissue. A biopsy requires a sample of solid bone tissue. In both tests, samples are usually taken from the bone marrow in the pelvis. The amount of plasma cells in the samples is then measured. A diagnosis of multiple myeloma is likely if more than 10% of the cells in your bone marrow are plasma cells.

The above list is a general overview of several tests that may be used to diagnose multiple myeloma. Your healthcare team may have performed additional or different diagnostic tests. If you have any questions about the tests used for your diagnosis, please consult your healthcare team.

Diagnostic Criteria for Multiple Myeloma

A diagnosis of multiple myeloma is given when all three of the following criteria are met:

When the bone marrow biopsy shows an excess amount of myeloma cells,
When M-protein is found in the blood or urine, and
When there is some evidence of organ or tissue-related damage to the body as a result of myeloma (and not another cause), such as bone lesions, kidney failure, anemia, or high calcium levels in the blood.

The clinical manifestations of end-organ damage needed for a diagnosis of multiple myeloma consists of a group of findings known as CRAB, which stands for:
C - Elevated hypercalcemia
R - Renal failure
A - Anemia
B - Bone lesions

Staging

Based on the information from your diagnostic tests, your healthcare provider may stage your disease. Staging is a way for your healthcare provider to classify and quantify how extensive the cancer is. Then, these pieces of information can be used to make treatment decisions.

There are two different staging systems for multiple myeloma:

The Durie-Salmon System, which is an older system, classifies multiple myeloma into one of three stages.
The International Staging System (ISS) for multiple myeloma is a newer staging system that also divides multiple myeloma into three stages.

view Staging Systems

Durie-Salmon Staging System

The Durie-Salmon Staging System was developed in the 1970s and is best used as a measure of the overall amount of malignant plasma cells present in the body. This system classifies disease into one of three stages based on findings of the following four factors:

1. The amount of abnormal M-protein in the blood or urine
2. The amount of calcium in the blood
3. The severity of bone damage as seen on x-rays
4. The amount of hemoglobin in the blood

Based on these factors, the disease is classified into one of three stages. A description of each stage is presented in the table below.

Stage 1

All of the following features must be present:

Hemoglobin level is only slightly below normal
No bone damage
Normal blood calcium levels
Low levels of M-protein in the blood or urine

Stage 2

Displaying features that do not meet the definitions of either Stage I or Stage III

Stage 3

One or more of the following features must be present:

Low hemoglobin level
High blood calcium level
Three or more areas of bone damage
High levels of M-protein in the blood or urine

The International Staging System (ISS)

The ISS was published in 2005 intent of simplifying the staging process. Like the Durie-Salmon system, the ISS also divides cases of myeloma into three stages, but it only uses two measurements:

Levels of serum beta-2 microglobulin in the blood and urine.
- This is a small protein found on the surface of many cells; high levels may be a sign of certain diseases, including multiple myeloma
Levels of serum albumin in the blood
- This is the main protein found in blood; low levels may occur in people experiencing liver and kidney disease

Stage 1

Serum beta-2 microglobulin is low and the albumin level is high

Stage 2

Having measurements that do not meet the definitions of either Stage I or Stage III

Stage 3

Serum beta-2 microglobulin is elevated

The higher the level of serum beta-2 microglobulin, the more advanced the stage
The lower the level of serum albumin, the more advanced the stage

TAKE A CLOSER LOOK: FREE LIGHT CHAINS

Light chains are small proteins found in antibodies. While there are two types of light chains, kappa (Îº) and lambda (Î»), each plasma cell produces only one type.

Typically, light chains are produced within the plasma cell and are then assembled to form a whole immunoglobulin. However, when these chains are not attached to other parts of the immunoglobulin, they are called free light chains. For unknown reasons, plasma cells typically produce more light chains than are required to create the whole immunoglobulin. So, these extra light chains enter the blood stream. One specific type of light chain is called Bence Jones proteinâ€”and elevated levels of this protein may be in your blood or urine.

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