MM101 Articles

Written by Peter Tischler

 

 

 

North Texas Myeloma Support Group

http://northtexas.myeloma.org

http://northtexas.myeloma.org/mm101.pdf

 

 

 

 

¨      Myeloma 101. 3

¨      What is Multiple Myeloma?. 4

¨      The Myeloma Cell 5

¨      Myeloma Protein. 6

¨      The supporting Cast 8

¨      How Myeloma Affects Us. 9

¨      Different Types of Myeloma. 10

¨      Staging Myeloma. 12

¨      Testing - Blood Tests. 14

¨      Testing - Urine Tests. 16

¨      Testing – Scans. 18

¨      Testing – Other 21

¨      Treatment – Overview.. 23

¨      Treatment – Standard/Frontline. 25

¨      Treatment – Maintenance. 27

¨      Treatment – Transplants. 29


 

Myeloma 101                                 

These articles are written by Peter Tischler and are based on information gathered from a variety of medical and experiential sources over the past eight years. 

Myeloma 101 will try to explain the basics of our disease, diagnostic tests that are used, and treatments for the disease. 

Because there are differing levels of education, understanding of things medical, and interest in details, I have attempted to address all levels by explaining things in three layers:

·        Simple Explanation ( written in the color green)

·        More Details (written in the color blue)

·        More Technical Stuff (written in the color orange)

For up-to-date copies of these articles, you may choose to go directly to the articles at http://northtexas.myeloma.org/mm101.html or you may choose to go to the North Texas Myeloma Support Group’s website, http://northtexas.myeloma.org/newsletters.html  and choose “Myeloma 101”.

What is Multiple Myeloma?

 

Simple Explanation:

Multiple myeloma is a blood cancer. Other better-known blood cancers are leukemia and lymphoma.  It is called “multiple” because this cancer typically causes problems in more than one place in the body. 

The occurrence of myeloma is on the rise in the United States.  It currently has no known cure, but it is usually slow-growing and can be treated.  Myeloma has long been known as a disease of the elderly, but in recent years more and more younger people are being diagnosed with this cancer.

The cause of myeloma is not known, but it is thought that certain industrial products, farm fertilizers and pesticides, and radiation might all be contributing factors. 

There is no known hereditary factor associated with myeloma, although the occurrence of myeloma within families is being studied.

Multiple myeloma is slightly more likely in men than in women, and it is more common in African-Americans than in Caucasians.

Common problems seen at and prior to diagnosis are tiredness, weakness, infections, bone pain, and fractures.  

 

More Details:

Multiple myeloma is called a hematological cancer and affects the plasma cell, one of the blood cells that comprise the immune system.  The plasma cell is an immunoglobulin-secreting cell.  In other words, it is a “factory” that the immune system creates in order to generate massive amounts of antibodies, or immunoglobulins, in order to fight “invaders.” Immunoglobulin is a protein that, when produced by a malignant plasma cell, is called myeloma protein or m-protein.

Normal bone marrow contains less than 5% plasma cells. In multiple myeloma there are usually more than 30% plasma cells and that number can increase to over 90%.  

There are over 15, 000 new cases of myeloma in the U.S. each year, representing 15% of all blood cancers and 1% of all types of cancer.

According to the International Myeloma Foundation (IMF), “There is only a weak family tendency to develop myeloma. Approximately 3-5% of patients with myeloma give a history of myeloma or a related blood/bone marrow condition within the extended family. Thus far, no specific gene has been linked to this myeloma tendency.”

 

More Technical Stuff:

Multiple myeloma is an incurable malignancy of immature, isotype-switched, immunoglobulin-secreting plasma cells that accumulate in the bone marrow, leading to marrow failure and bone destruction.

The Myeloma Cell

 

Simple Explanation:

In multiple myeloma, as with any cancer, there has been a mutation of a certain cell. From that single mutated cell a great many identical cells have grown.  In the case of myeloma, the particular cell that had the mutation is known as a “plasma cell.”  In every human body there are many health plasma cells.  In the body of someone with myeloma there are both healthy plasma cells and the mutated plasma cells. 

The mutated (malignant) plasma cells, or myeloma cells, continuously multiply. Large numbers of myeloma cells form tumors. Tumors of myeloma cells can grow inside bones or on the outside of bones.  Good blood cells are crowded out and the bones themselves are often damaged, leading to fractures.

All of the myeloma cells are identical and they are all deformed.  They serve no useful purpose because they are defective.  Normal plasma cells automatically die after a period of time, but the myeloma cells have lost the ability to die.  Your immune system tries to kill them but is not able to get the job done.

 

More Details:

The malignant plasma cells, or myeloma cells, have an affinity for the bone marrow environment where they establish a destructive relationship with other stromal (bone matrix) cells.  The myeloma cells secrete substances that cause bone destruction and lead to a further proliferation of the myeloma cells.

All of the myeloma cells are identical and are, therefore, called monoclonal.  Depending on when the mutation took place, for a given individual, the myeloma cells will produce certain “fragments” of immunoglobulin (antibodies) that can be used to identify the type of myeloma.

From a single mutated plasma cell, trillions of identical myeloma cells (clones) are eventually created.  Those myeloma cells may form one or more soft tumors (called plasmacytomas) and/or may infiltrate the marrow inside certain bones, usually the femur, humeris, pelvis, vertebrae, ribs, and skull. 

Aggregations of myeloma cells are usually associated with bones, whether from the inside, the outside or both. The damage to the bone is known as a lesion.  Lesions show up on imaging studies (x-ray, MRI, scans).

When the aggregations of myeloma cells occur inside the marrow-producing bones, the healthy cells of the immune system (e.g. red blood cells, white blood cells, platelets) are crowded out. In such cases, the immune system is compromised, causing increased risk of infections, tiredness, and weakness.

 

More Technical Stuff:

The myeloma cells establish a destructive relationship with bone remodeling cells called osteoclasts. Myeloma cells produce soluble signals called cytokines that activate the bone resorbing osteoclasts.  Other cytokines that are osteoclast activating factors (OAFs) are lymphotoxin, interleukin-1b (IL-1b) and interleukin-6 (IL-6).  In response, the osteoclasts and other stromal cells secrete even more IL-6, which stimulates the production of more myeloma cells. 

With myeloma, there are two malignant cell populations: a slowly proliferative plasmablast (a plasma stem cell) and a slightly more differentiated plasma cell that cannot proliferate.  That fact will be important when we get to treatment options.

Myeloma Protein

 

Simple Explanation:

Myeloma cells are malignant plasma cells, and the purpose of plasma cells is to pump out vast quantities of a protein called immunoglobulin.  In the case of the myeloma cells, the protein that is created is defective, just as the myeloma cell itself is defective.  Almost all cases of myeloma (99%) have the additional problem of an excess of this defective protein, which is also called myeloma protein, or m-protein. 

Besides the problems that the myeloma cells can cause, the myeloma protein may cause further problems that have to be addressed.  But first we need to understand a few things about the myeloma protein.

Good plasma cells create a variety of these proteins, depending on the reason why the plasma cell was created.  In other words, the bodily invader caused a particular type of plasma cell to be created.  Therefore, medical people refer to your type of myeloma according to the kind of protein it creates. 

One way to measure the extent of your disease is to measure the amount of myeloma in your bone marrow.  Another, and simpler, test is to measure the amount of myeloma protein that you have in your blood and urine.

Now, about the problems that the myeloma protein may cause.  In order to get rid of the excessive protein that is being created by the myeloma cells, the kidneys must work very hard to do the job.  In fact, the kidneys may become overwhelmed and the myeloma patient may develop kidney problems or even kidney failure.  Great care must be taken by your oncologist and you to prevent this from happening.  Your job is to drink plenty of water every day.

Another problem that may result from the excess protein is, in rare cases, thickening of the blood, leading to stress on the heart and other organs. 

 

More Details:

Your type of myeloma relates to the kind of protein, or immunoglobulin, that is created by your myeloma cells.

All immunoglobulin proteins are comprised of two parts: a heavy-chain (so called because that part of the molecule is heavier in weight) and a light-chain (this part weighs less).  The heavy-chain fragments of the molecule are known as IgA, IgG, IgD, IgE, or IgM.  The light-chain fragments are known as kappa or lambda and are also known as Bence-Jones protein. 

Your defective myeloma cells may produce a heavy-chain fragment only, a light-chain fragment only, a molecule with both heavy- and light-chain components (the most common), or none of the above (only about 1% are non-secreting, or non-secretory myeloma).

Therefore, your myeloma may be called something like IgG, or IgA lambda, or maybe just kappa light-chain.  Don’t worry about the difference in those names, at present, but be aware that it’s a way for the medical people to classify your particular myeloma.

One more thing to note about the myeloma protein: the heavy-chain protein (beginning with the letters Ig) is quantified by testing your blood, and the light-chain protein (kappa or lambda) is usually quantified by testing your urine.

The stress to your kidneys from the excess protein can be measured and controlled (to some extent) by your doctor. Keeping the kidneys healthy with plenty of fluids is something that the patient has some control over.  The light-chain fragments are more damaging to the kidneys than the heavy-chain fragments and lambda light-chain is the most damaging. 

 

More Technical Stuff:

The immunoglobulin secreted by the myeloma cells is called m-protein, where the “m” can stand for myeloma or monoclonal.  When the amount of myeloma protein is measured and shown on a graph, the excess protein forms a spike on the graph and is known as the “m-spike.” 

As previously mentioned, there are heavy- and light- chain fragments. In 57% of patients it is IgG, in 21% it is IgA, in 2% it is IgD, and only extremely rarely (>1%) IgM or IgE.  In 18% of patients only a light-chain is secreted (Bence-Jones protein), which because of its low molecular weight is excreted in the urine, and in 1%-2% no immunoglobulin is secreted.  This last category is known as non-secreting or non-secretory myeloma.

The supporting Cast

 

Simple Explanation:

We’ve talked about the myeloma cells and the protein that they secrete.  But the myeloma cell also secretes other molecules that have a complex interaction with the many cells in the bone marrow environment. The result is a cycle of destruction whereby the myeloma cell creates other cells that destroy bone; but the cells that destroy bone secrete substances that cause the myeloma cells to proliferate. This cycle of destruction, unless broken by treatment, may result in severe damage to your skeleton.

 

More Details:

The myeloma cell secretes not only immunoglobulin but other molecules called cytokines that interact with the bone marrow microenvironment.  Some of those secreted cytokines are called Osteoclast Activating Factors (OAFs), which cause a proliferation in the osteoclasts, which degrade bone.  The osteoclasts in turn, along with other activated stromal cells, produce Interleuken-6 (IL-6), which is a major growth factor for myeloma cells. 

To make matters even worse, the myeloma suppresses the osteoblasts, which are the bone builders in the remodeling that occurs in a person without myeloma.

 

More Technical Stuff:

Over the last several years, as more is understood regarding the interaction of the various players within the bone marrow matrix, new treatment ideas have become possible.  In addition to treating the myeloma directly, protection of the bone matrix has become possible with drugs such as the bisphosphonates (e.g. Aredia and Zometa).  Also, disruption of the “cycle of destruction” may be possible with drugs that suppress IL-6 and other MM growth factors; another treatment being investigated is the infusion of OPG in order to bind the RANK ligand that would otherwise bind to RANK, thus neutralizing the signaling chain that leads to osteoclast formation and ensuing bone destruction.  In fact, there are an incredible number of molecular interactions, any one of which may turn out to be a solution to the dual problem of bone destruction and myeloma cell proliferation.

 

How Myeloma Affects Us

 

There are three typical ways that myeloma affects a person.  First, myeloma suppresses the immune system, which leaves the person more likely to get sinus, respiratory, and other infections.  A suppressed immune system may mean anemia (weakness, tiredness) and low platelets (slowness to heal). 

Second, myeloma affects the skeleton.  Lesions may lead to compression fractures in the spine, broken ribs, arms, shoulders, or legs.  Bone pain is often a side effect of the disease.

Third, the myeloma protein may affect the kidneys to a significant degree.  It is not uncommon for patients to have kidney damage and even kidney failure at diagnosis.

 

More Details:

There are a great number of cells, molecules, proteins, and enzymes that interact in the bone marrow.  Every change within that population causes reactions, sometimes a veritable cascade of reactions.  Myeloma changes the balance of the marrow and bone environments, but in ways that are unique to each individual.  However, some of the changes are fairly typical.

There is only so much room inside the marrow-producing bones (e.g. pelvis, femur, humeris, rib, vertebra, clavicle, skull), and all the cells necessary for the care and maintenance of your body are found there.  When a huge population of myeloma cells is produced inside those bones, there becomes less and less room for the “good” cells, which are crowded out.  Therefore, it is typical that a person with myeloma has fewer red blood cells, white blood cells, and platelets.  Those deficits often result in anemia, increased infection or inability to control infections, and a decreased ability for wounds to heal and an increased instance of bruising.

Bone destruction is a primary feature of multiple myeloma.  In recent years, much attention has been paid to myeloma bone disease, especially after the development of a class of drugs (bisphosphonates) that greatly help that problem. 

There is often some confusion about the role of the plasmacytoma and the lesion, as defined in myeloma.  A plasmacytoma is simply an aggregation of myeloma cells – a soft tumor.  A lesion is something that has made a defect on one of your bones.  Often, a soft tumor has grown on and into one of your bones, thus forming a lesion.  Sometimes, however, the plasmacytoma may grow either inside or on the outside of a bone without harming the bone (i.e. no lesion).  But most of the time there is slow and steady destruction of the bone – unless the progression is slowed or stopped.

The large amount of monoclonal protein can clog up your bloodstream and cause lots of problems to your systems, which have a hard time eliminating it. The kidneys and heart are two of the primary organs that can get overwhelmed by this "sludge" created by the myeloma cells. People with light-chain-only myeloma create too much light-chain protein (kappa or lambda). This light-chain protein has a small enough molecular size that it passes into and through the tubules of the kidneys into the urine. In great enough quantities, however, it can overwhelm the kidneys and cause kidney damage or even renal failure. Sometimes the light-chain protein combines with other proteins to form a substance called “amyloid” which is even more dangerous to the kidneys, spleen, liver and other organs.

 

More Technical Stuff:

Bone pain occurs in approximately 75% of patients and about 50% have radiologically detectable myeloma-related skeletal lesions at diagnosis.

Hyperviscosity sometimes occurs in cases of IgM myeloma (rare), IgA, or IgG3 subtype. 

Polyneuropathy is observed in 5%-15% of myeloma patients, but as many as 50% of patients may have subclinical neuropathy.

Hypercalcemia is found in about a third of patients at diagnosis and is usually associated with advanced disease and, in particular, with extensive osteolytic bone lesions.  Such patients may develop acute nausea/vomiting or confusion due to hypercalcemia or uremia.

 

Different Types of Myeloma

 

Simple Explanation:

There are several different “varieties” of myeloma.  One of them (you may hear the term MGUS) is not really myeloma, but only a benign condition that may, in time, become myeloma.  All other varieties are malignant.  The benign MGUS variety is usually not treated.

Another term you might hear is “Smoldering Myeloma.” This term is used to identify a person with no bone problems, no anemia, no kidney problems, and a relatively low amount of myeloma cells in the bone marrow.  This type of myeloma is usually not treated as long as it remains within the above criteria.

A third term used is “Indolent Myeloma.”  It is similar to “Smoldering Myeloma,” but allows mild anemia and a few small bone problems (lesions).  The amount of myeloma cells could be slightly higher than with Smoldering Myeloma.  Treatment may or may not be used, depending on the treatment philosophy of the oncologist.

“Solitary Plasmacytoma of Bone” is a term used to describe a case of myeloma where the only evidence of the disease is localized in a single soft tumor on or in a bone.  The significance of SPB is that radiation of that location may eliminate the myeloma from the patient’s body. 

“Extramedullary Plasmacytoma” refers to a case of myeloma where there is a soft-tissue plasma cell tumor. Such tumors usually arise in the upper respiratory passages.

Other than the above exceptions, Multiple Myeloma is given that name because it usually occurs in more than on location, usually associated with the marrow-producing bones in the body.  When progressing from a lesser form of the disease, myeloma is sometimes referred to as “overt myeloma” or “frank myeloma.” 

 

More Details:

All of the types of disease with which we are dealing fall under the heading of “Monoclonal Gammopathies.”  They are characterized by a proliferation of a single clone of plasma cells producing a homogeneous (monoclonal) protein (m-component, m-protein, paraprotein). 

MGUS is an acronym that stands for Monoclonal Gammopathy of Undetermined Significance.  It means that there is relatively small monoclonal component in either the blood (IgG, IgA, etc.), or urine (kappa, lambda) and a relatively small infiltration of the bone marrow with plasma cells (< 10%).  There are no symptoms of disease and the person is usually in good health.  The disease is stable (until, or unless, it progresses to myeloma) and need only be watched.

Smoldering Myeloma (SMM) is characterized with IgG > 35 g/l or IgA > 20 g/l and/or Bence-Jones protein < 1.0 g/24 hrs.  Bone marrow infiltration with plasma cells is > 10% but < 20%.  There are no renal problems, anemia, hypercalcemia and no bone marrow lesions on skeletal survey.

Indolent Myeloma (IMM) is characterized with IgG < 70 g/l or IgA < 50 g/l and/or Bence-Jones protein < 1.0 g/24 hrs.  Bone marrow infiltration with plasma cells is > 20% but < 30%.  There are no renal problems or hypercalcemia, no more than mild anemia, and no more than two or three small lytic lesions (but no compression collapse).

Multiple Myeloma (MM) is characterized by the presence of one or more of the following major criteria: plasmacytomas, infiltration of the bone marrow > 30%, monoclonal IgG > 35 g/l, monoclonal IgA >20 g/l, and Bence-Jones protein > 1 g/24 hrs.  Also, one or more of the following minor criteria: lytic bone lesions, suppression of the normal immunoglobulins.

 

More Technical Stuff:

There are many other factors that can lead to a diagnosis of multiple myeloma, such as the markers Beta-2-Microglobulin (B2M), C-Reactive Protein (CRP), hypercalcemia due to bone destruction, and Plasma Cell Labeling Index (PCLI).

These will be discussed further in the section on “Staging Myeloma.”

There will continue to be advances in understanding the genetics of myeloma.  There has already been important work done to categorize different kinds of myeloma according to specific gene translocations.  One of those genetic variations, known as “chromosome 13 deletion” is known to have a less favorable outcome than others.  For now, however, the science of differentiation doesn’t lead to better, or more selective, treatment for any given genetic variation of myeloma. 

Staging Myeloma

 

Simple Explanation:

Staging for a disease has two purposes.  First, it tells the medical team, and the patient and caregiver, how far the disease has progressed.  Generally, the lower stage number is better news for you and the medical team.  Knowing the stage can be a mixed blessing for you.  Hearing that your myeloma has a relatively low stage number can make you feel better about your future, while hearing that it’s a high number can be frightening.  This is deceptive, because it’s often not the stage that’s important but rather the aggressiveness or trend of the disease.  For the most part, knowing the stage does little for the patient and the family. 

Second, the stage can sometimes determine the treatment you will receive.  Some clinical trials might allow only, say, stage 3 patients.  Sometimes the lowest stage patients might be given a fairly benign treatment rather than a harsh one.  Quite often, however, patients will be treated pretty much the same, by a given oncologist, regardless of the stage. 

An additional point: staging can be somewhat an “art” as well as science.  Although most staging systems have fairly strict criteria, there is some gray area between stages.  One oncologist might stage a patient as stage 2, while another might call it stage 3. 

One final point:  Knowing a stage number doesn’t mean much unless you know which staging system is being used by the oncologist.  There are four different staging systems in use at this time (although only one is most commonly used), so you might get two different stage numbers from two different consultations, even though they really mean the same thing.

 

More Details:

There are four usual staging systems in use as of this date.  In order of usage, they are:

·        The Durie/Salmon Staging System

·        The SWOG (SouthWest Oncology Group) Staging System

·        The Durie/Salmon Plus Staging System

·        The new International Prognostic Index (IPI) Staging System

At this date, most patients have been staged with the Durie/Salmon Staging System.  This system has three stages (I, II, and III) and each stage has a sub-classification indicating renal (kidney) function.  The factors weighed for the three stages are hemoglobin value (anemia), serum calcium value (bone destruction), bone x-rays results (lytic lesions), m-component production rates (IgG, IgA, etc. and kappa, lambda), and myeloma cell mass (tumor burden) from a bone marrow biopsy and aspiration. Sub-classification (“A” or “B”) refers to the serum creatinine value (renal function).

The SouthWest Oncology Group (SWOG) Staging System is a simple prognostic classification system that has four stages (I, II, III, and IV).  This system weighs only two factors: serum beta-2-microglobulin (b2m) and serum albumin.  Stages I and II result from normal or higher b2m, respectively.  Stages III and IV result from high b2m, and normal or low serum albumin, respectively.

The Durie/Salmon Plus Staging System uses the factors used in the standard Durie/Salmon Staging System for stages IB, IIA and IIB, IIIA, and IIIB, although it adds the criterion of number of focal lesions to the I, II, and III stages.  Stage IA is reserved for smoldering or indolent myeloma if there is a single plasmacytoma and/or limited disease seen on imaging studies.  The sub-classification (A or B) weighs the factors serum creatinine, platelet count, and presence or absence of extramedulary disease.

The International Prognostic Index (IPI) Staging System is a simple system similar to the SWOG system.  Like the SWOG system, it weighs only the two factors: serum beta-2- microglobulin (b2m) and serum albumin.  Stages I results from normal-to-low b2m and normal-to-higher serum albumin.  Stage II results from either normal-to-low b2m and low serum albumin, or low-to-medium b2m.  Stages III results from high b2m.  There is no Stage IV in the IPI Staging System.

 

More Technical Stuff:

Durie Salmon Staging System:

   Stage I

·        All of the following:

·        Hemoglobin value > 10 g/l

·        Serum Calcium value normal or < 10.5 mg/dl

·        Bone x-ray shows normal bone structure or solitary bone plasmacytoma

·        Low m-component production rates (IgG < 5.0 g/dl or IgA < 3.0 g/dl, urine light-chain < 4 g/24h)

·        Myeloma cell mass (in the whole body) 600 billion cells/meter squared or less

   Stage II

·        All of the following:

·        Fitting neither Stage I or Stage III

·        Myeloma cell mass (in the whole body) 600 to 1,200 billion cells/meter squared

   Stage III

·        One or more of the following:

·        Hemoglobin value < 8.5 g/dl

·        Serum Calcium value > 12.0 mg/dl

·        Advanced lytic bone lesions

·        High m-component production rates (IgG > 7.0 g/dl or IgA > 5.0 g/dl, urine light-chain > 12 g/24h)

·        Myeloma cell mass (in the whole body) > 1,200 billion cells/meter squared

   Sub-classification (either A or B)

·        A: relatively normal renal function (serum creatinine value) < 2.0 mg/dl

·        B: abnormal renal function (serum creatinine value) > 2.0 mg/dl

Testing - Blood Tests

 

Simple Explanation:

There are two different reasons for testing in myeloma.  The first is to confirm a diagnosis of the disease and determine the severity of the patient’s condition.  The second is to monitor the patient through periods of treatment and plateau (remission). 

Basically, there are three kinds of tests for myeloma:

·        Blood tests (we will include the bone marrow biopsy in this group)

·        Urine tests

·        Imaging tests

In order for your doctor to know the extent of the disease and, subsequently, the success of a treatment, there are a variety of blood tests that, together, create a picture.  It’s much like putting together a jigsaw puzzle; any given piece of the picture puzzle is, by itself, inadequate.  But when you’ve assembled all the pieces, the picture becomes clear.

Having said that, I’ve met many MMers who simply want to understand, and follow, their “myeloma count” and their “blood counts.”  When they refer to the “myeloma count,” they really mean the number their oncologist mentions when he’s talking about the amount of myeloma protein in their blood. Remember that myeloma cells produce lots of myeloma protein and that’s what can be measured in the blood.  However, that’s only true for about 80%-85% of MMers, as the others only create a myeloma protein that can be measured in the urine.  If you’re among the majority (the 80%-85%), then that protein value is the “myeloma count” for you.

The “blood counts” refer to the test called the CBC (complete blood count).  You might be told that your red blood cells are too low, or your white blood cells are too low, or you don’t have enough platelets.  That may delay your next treatment.  It might also cause your oncologist to order something to stimulate more of the cells that are lacking (e.g. Procrit, Neupogen).

 

More Details:

One of the fortunate aspects of myeloma is that for most of us there is a myeloma “marker” [a marker is a test result that can tell the physician, and you, how your disease is behaving].  The marker for myeloma is either the myeloma protein (m-protein) in your blood or the m-protein in your urine, or both.  Only a few people (1% - 2%) have a rare variant that has no such marker.  The primary blood test for both diagnosis and monitoring is called serum protein electrophoresis (sometimes called SPEP), which tests for the myeloma marker in the blood. 

The bone marrow biopsy can be important, because it can show the actual myeloma cells and the sample retrieved can be examined to determine the type of myeloma and may suggest how to treat the disease.  Your oncologist might say, for instance, “Your latest bone marrow biopsy shows that the plasma cells in your marrow have dropped from 60% to 15%.”

The complete blood count will often show how the patient has been affected by the disease (e.g. lowered red cell, white cell and platelet counts).  Those lowered counts often correlate to the patient’s being tired, prone to bruising, slow to heal, and open to infections.

The chemistry panel shows a variety of important counts, which may have been affected by the disease (e.g. calcium, creatinine).  These may indicate that your bones are being degraded, that your kidneys are stressed, or other ways in which the myeloma is affecting your body.

Several secondary markers that can be elevated when a disease is active in the body are also usually checked and tracked:  beta-2-microglobulin (B2M), C-reactive protein (CRP), and lactate dehydrogenase (LDH). 

A new blood test, which is growing in usage, can be very important to patients who have only urine myeloma protein or have no myeloma protein.  This test is called the FreeLite Test and it measures free monoclonal light chains in the blood.  Everyone has a certain level of these free light chains in their body, but those of us with myeloma will often have an excess, indicating that the disease is active.

 

 

More Technical Stuff:

The most important marker for MMers is the excess protein that is created by the myeloma cells.  But not all oncologists follow that marker the same way. Most will use the serum protein electrophoresis or the corresponding test against the urine (for those with light-chain-only myeloma). In some cases, in order to save money, the oncologist will only look at the total protein number that is available from the chemistry panel.  When there is myeloma protein in the serum, the total amount of protein is elevated above normal by that “abnormal” amount.  Therefore, it is possible to track the progress of the disease, and/or treatment, by the total protein.  It is not, however, possible to know if there are other problems that might be elevating the “good” protein, thus making total protein a poor way to track the myeloma. 

The serum protein electrophoresis test does not tell the doctor which of the immunoglobulins (IgG, IgA, etc) is the culprit.  In order for him to determine which of the immunoglobulins is your myeloma protein, a test called immunofixation may be performed. Still another test (either radial immunodiffusion or immunonephelometry) can quantify the amount of the monoclonal immunoglobulin.  Obviously, cost is a factor in testing, and you and your oncologist must decide how much information about your myeloma is enough.

The bone marrow aspirate and trephine biopsy (the more complete name of the test) can be very important if testing is going to be done with your actual myeloma cells.  Cytogenetics, immunophenotyping, and plasma cell labeling index are among such tests.  The bone marrow test has long been used as a confirmation of diagnosis and to quantify the amount of “tumor burden” (the degree to which myeloma cells have infiltrated the marrow).  The limitation of this test is that many myeloma patients have “focal” (myeloma clusters here and there) rather than “diffuse” (myeloma cells homogenously spread through the marrow) disease.  In the case of focal disease, it’s difficult to assure that the aspirate and biopsy will always hit an area representative of the patient’s disease.  Many oncologists no longer rely as much on this test unless there is a need for the marrow for further testing.

Complete blood count is very important to MMers with active disease, especially the red cell (RBC), white cell (WBC), and platelet counts.  Anemia is a frequent problem with myeloma and the RBC correlates well with that problem.  The risk of infection will correlate to the WBC value.  Lowered platelets can mean a risk of bleeding and bruising.  As the myeloma cells are controlled, the immune system can make for good cells and those counts will improve.

Chemistry panel shows many important values, but often MMers are most interested in the values that indicate whether or not their bones are being “eaten” by their disease (calcium), and whether or not their kidneys are being affected by the myeloma (creatinine).  When myeloma is active, cytokines are created that cause bone resorption.  As the bone is resorbed, lytic lesions form and calcium is a byproduct that may be detected in the blood.  Although creatinine is a good general indicator of kidney health, some oncologists order another test called the creatinine clearance in association with the 24-hour urine testing. 

Beta-2-microglobulin (B2M) is most effectively used at diagnosis.  This marker is affected by treatment and is, therefore, of limited value after diagnosis.  In addition, B2M, CRP and LDH may all be elevated in the course of problems other than myeloma. 

There are, of course, many other values that may or may not be important on your blood tests.  The important things are to understand the reason why any value is not within the reference range (that lab’s “normal” range) and to track each value over time, as with a spreadsheet.  Trends are more important than just the values at any specific time.

Remember that the reference range for your lab values may differ from the reference range for another MMer’s values.  Also, measurements may vary; one person’s reading might be in g/dl (grams per deciliter), while another person’s lab may use mg/dl (milligrams per deciliter).