Myeloma: Definition, Classification, Causes, Symptoms, Diagnosis and Treatment

It is a type of cancer that occurs in the bone marrow, in which there is an abnormal proliferation of plasma cells.

The cells, which are part of the white blood cells , have the normal function of producing the antibodies (immunoglobulins) necessary for the body’s defenses.

The immunoglobulins have a symmetric structure composed of two long or heavy chains and two light chains or short.

Each category is designated by a capital letter (IgA, IgD, IgE, IgG and IgM) according to the type of heavy chain (A, D, E, G or M).

Light chains are of two types: kappa (κ) and lambda (λ), an immunoglobulin can be named according to the class to which its heavy and light chains (eg IgAλ).

In a normal organism, there is a wide range of immunoglobulins capable of defending the organism against all aggressors.

Bone marrow is the “spongy” substance found in the center of the main bones of the body, producing three types of blood cells:

  • Red blood cells: they are filled with hemoglobin that carries oxygen.
  • Blood platelets: agglutinate in case of bleeding and participate in the formation of the clot that will stop the bleeding in progress.
  • White blood cells: they have a defense function of the body against foreign bodies and microbes play an important role in the functioning of your immune system. Neutrophils defend us especially against bacteria and lymphocytes against viruses.

B lymphocytes, after encountering an intruder (called an antigen), turn into plasma cells.

In myeloma, one type of plasma cell grows out of control, and therefore two things happen:

  1. Produce too many plasma cells (more than 10%) from the bone marrow (in healthy people, they represent 2 to 3% of the cells in the bone marrow). They can suppress the production of other types of cells, such as red blood cells and platelets.
  2. Produce a large amount of abnormal immunoglobulin (called M-Protein) causing the disappearance of normal immunoglobulins.

Abnormal plasma cells can also disrupt bone turnover mechanism: they stimulate the cells responsible for bone destruction (osteoclasts) and inhibit the activity of the cells responsible for the production of new bone (osteoblasts).

This leads to a gradual weakening of the bones, with gaps visible on images and an increased risk of fractures.

Therefore, bone damage is very common in myeloma.

Cause of myeloma

To date, no cause for myeloma has been identified.

Research suggests a possible link to a lowered immune system, certain professions, exposure to certain chemicals, or exposure to ionizing radiation.

However, there is no conclusive link, and in most cases, myeloma occurs in people who do not have risk factors.

Myeloma could be the result of several factors acting simultaneously.

Although genetic changes are present in myeloma cells, there is currently no evidence to indicate that myeloma is an inherited disease, its occurrence in more than one member within the same family is rare but possible.

Myeloma is not contagious or communicable.

Symptoms of myeloma

The early stage of myeloma often has no symptoms.

In the presence of symptoms, these can be vague and resemble the symptoms of other diseases.

The most common symptoms can be:

  • Bone pain: Osteolytic injuries weaken the bones and cause vertebrae to fracture or crush. Almost 70% of myeloma patients see a doctor because of pain, which can cause all bones to be affected.
  • Fatigue, weakness, paleness – The increasing number of myeloma cells can slow down the production of red blood cells in the bone marrow, leading to anemia. A large amount of abnormal protein makes the blood less fluid, which is called blood hyperviscosity.
  • Recurrent and severe infections: due to the decrease in the production of certain white blood cells, normal immunoglobulins.
  • Loss of weight and appetite: bone breakdown releases excessive amounts of calcium into the blood (hypercalcemia).

Hypercalcemia is accompanied by various symptoms including loss of appetite, fatigue, muscle weakness, agitation, difficulty concentrating, confusion, constipation, increased thirst, more frequent urination, nausea, and vomiting.

Myeloma is the second most common blood cancer after non-Hodgkin lymphoma , accounting for about 1% of all cancers.

Its prevalence (that is, the number of cases reported at any given time) varies by sex, age, or race.

Myeloma affects more men than women and is diagnosed more frequently at older ages (60 to 75 years), affecting twice the black population than the white population.


Blood test

The diagnosis of multiple myeloma is often evoked by tests performed from a blood sample.

The main one, called serum protein electrophoresis, aims to analyze the proteins present in the blood.

The test can determine if there is a monoclonal immunoglobulin (forming a clearly identifiable peak, sometimes referred to as “monoclonal peak”).

Complementary tests are then used to determine exactly which immunoglobulin is for quantification.

Electrophoresis is also performed on urine, being part of the monoclonal immunoglobulin that is frequently detectable and is called Bence-Jones protein or light chains.

The blood test can determine the degree of anemia to find thrombocytopenia, evaluate the function of the kidneys and measure calcium levels, parameters necessary for their care.

Bone analysis

Bone x-rays can show changes in bone structure and the presence of holes (osteolytic lesions).

The skull, spine, humerus, ribs, pelvis, and femur are usually radiographed.

Other imaging techniques can be used, such as magnetic resonance imaging, computed tomography, or positron emission tomography, which are more sensitive than standard X-rays and also allow us to observe possible consequences of the disease in other organs, such as the spinal cord.

Bone marrow analysis

Bone marrow samples should be taken to determine the number of plasma cells.

The marrow is usually taken from the pelvis or sternum (aspiration only) and there are several ways to collect it:

  • Bone marrow collection: a needle is used for this practice. In addition to examining the sample under the microscope, one can proceed to study the cytogenetics of plasma cells, which is a prognostic element.
  • Bone marrow biopsy: A biopsy needle is inserted into a bone and, thanks to a rotational movement, a small sample of bone tissue is collected on the needle. The biopsy is performed at the same time as the puncture and is complementary, especially if the puncture fluid is not representative.
  • Biopsy of a bone, such as a vertebra: This is done if analysis of the bone marrow does not allow the diagnosis.

Classification and stages of myeloma

Myeloma is classified according to the results of diagnostic tests; a stage is assigned, it corresponds to the extent of the disease.

Staging and classification are helpful in determining treatment options.

Monoclonal paraprotein of undetermined importance

This is a low concentration of an abnormal immunoglobulin with less than 10% plasma cells in the bone marrow and no symptoms or organ damage that can be attributed to it.

This is a frequent situation, especially when the patient is elderly (3% in those over 70).

This is a precondition for the development of myeloma.

The risk of progression to true myeloma is estimated at 1% per year, especially if the paraprotein rate is greater than 15 g / l or if it is an immoglobulin A.

Therefore, this biological anomaly must be monitored over time.

Isolated plasmacytoma

This is a rare situation of a single bone lesion with no evidence of bone marrow abnormality, it is treated differently often by radiation therapy.

Asymptomatic myeloma

This diagnosis is made if there is a paraprotein measured over 30 g / l or more than 10% of plasma cells in the bone marrow without evidence of organ damage: no anemia, no bone damage, no hypercalcemia or kidney failure .

In addition to the abnormal protein and plasma cells in the marrow, there is damage to various organs such as the bones and kidneys.

Active or symptomatic myeloma

The process of staging the myeloma is essential to establishing effective treatment.

The most widely used system is the Durie and Salmon classification, which distinguishes three stages of myeloma.

The first stage corresponds to an asymptomatic disease, with a low monoclonal peak and the absence of bone lesions.

Stages II and III refer to the presence of biological symptoms (anemia, hypercalcemia) and a high monoclonal peak and bone lesions.

These stages reflect or estimate the tumor mass or the degree of the disease.

Determination of stage and search for prognostic factors:

  • Stage I: asymptomatic, low tumor mass.
  • Stage II: Intermediate.
  • Stage III: active and high tumor mass.

The larger the tumor mass, the more the disease can be considered progressive and therefore needs to be treated.

But there are other gravity factors that come into play. This is the case, in particular, of the level of β2-microglobulin.

Produced by plasma cells, this protein is a marker of disease activity. The higher the rate, the more evolutionary the myeloma.

The existence of abnormalities acquired during the disease in certain chromosomes is also an important prognostic factor.

Kidney function is also an important element.

Many drugs used to treat myeloma are cleared by the kidneys.

If kidney function deteriorates, treatment will be more complicated.

Treatment plans or therapeutic strategies will depend on the age and general condition of the patient, the stage or classification and prognostic factors of the disease and the symptoms and possible complications of the disease.

Myeloma treatment

Myeloma is a treatable disease that most often responds well to chemotherapy and radiation therapy.

The goal of treatment will be to obtain the strongest possible response to the disease, which will ensure the longest remission and prolongation of life span.

But, even if the complete disappearance of the disease is observed (disappearance of the abnormal protein in the blood and urine, normalization of the bone marrow examination), the myeloma can recur.

Currently, scientists believe that myeloma remains an incurable disease and should be considered a chronic disease with phases of progression and remission.

Undoubtedly, the advancement of new drugs and new therapeutic strategies make it possible to prolong the periods of remission and the life expectancy of patients.

The other goals of treatment are to relieve pain and other signs of the disease and to maintain a good quality of life for as long as possible.

These drugs are a synthetic form of a hormone secreted by the adrenal glands, known as prednisone , methylprednisolone, or dexamethasone.

They are available in oral or intravenous form.

In the case of myeloma, they are almost always associated with other treatments, are notable pain relievers, and constitute the emergency treatment of the disease.

These drugs are responsible for mood swings with nervousness and insomnia, weight gain with swelling of the face, gastric irritation.

They also promote diabetes, high blood pressure, loss of muscle and bone mass (osteoporosis), and infections.

When taking corticosteroids, it is necessary to limit the intake of salt and sugars, take it rather in the morning and at mealtime; in case of stomach pains, a treatment will be prescribed.

The drug administered orally and intravenously at high doses in the case of transplantation, to kill cancer cells, is melphalan (Alkeran).

The toxicity of this treatment is mainly blood and when used orally, it is generally very well tolerated (little digestion disorder and no hair loss).

Other chemotherapy drugs can be used, but more rarely: such as Endoxan, platinum salts, Adriamycin and its liposomal derivatives (Caelyx).

High-dose chemotherapy, high-dose Melphalan, kills more myeloma cells than traditional treatments, but at the cost of a prolonged loss of normal bone marrow function.

To limit this, the patient is injected with stem cells that have been harvested beforehand.

Practically, during the beginning of myeloma treatment, blood stem cells are stimulated by 4 to 5 days of growth factor (Neupogen – Granocyte).

These stem cells can then be harvested through cytepheresis, which is a method of separating the different cells from the blood to keep only the stem cells that will then be stored until they are used.

A cytapheresis session lasts approximately 4 hours and is performed externally or during a short hospital stay.

Since it involves the patient’s own cells, the autologous transplant method is called and there are no compatibility or donor search problems.

After the first phase of treatment for the so-called induction myeloma, which makes it possible to correct the main symptoms of the disease, high-dose chemotherapy with stem cell autotransplantation aims to amplify the response already achieved and tend towards the complete disappearance of the disease. .

High-dose chemotherapy is very toxic: infection, digestive disorders, such as total loss of appetite, thrush and diarrhea, bleeding, hair loss.

To limit and counteract these risks, this procedure requires a hospital stay in a sterile environment for approximately 3 weeks.

The administration of melphalan is rapid (1 hour) followed 48 hours later by the infusion of the stem cells by simple transfusion.

Recovery of sufficient blood cell production takes about 15 days.

This procedure is ultimately harmless (1 to 2% of deaths) as long as it is applied to patients younger than 65 to 70 years of age and with good heart and lung function.

Several intensive treatments can be performed on the same patient if the result of the first treatment is not sufficient (tandem transplantation) or during a later course of the disease.

The transplanted cells come from another person called a compatible donor.

This donor is a family donor (brother or sister only) and a non-family donor, known as an unrelated donor.

To be a donor, a good tissue match is required.

This type of transplant is associated with more risks: infection and especially, what is called the graft versus host reaction – knowing the patient’s tissues are attacked by the donor’s immune cells – this reaction can be fatal.

The main purpose of preparing for this transplant is to prepare the recipient’s body to tolerate the transplanted cells, this procedure is called a mini allogeneic transplant.

Thalidomide is effective against myeloma, probably by counteracting the nutritive circulation of myeloma cells (called an antiangiogenic effect).

Thalidomide and its derivatives are also considered “immunomodulatory.”

Bone damage is responsible for pain: all pain treatments, including those derived from morphine, are allowed.

On the other hand, one must be very careful with anti-inflammatories that can aggravate the malfunction of the kidneys.

Anemia is a common symptom of myeloma.

To treat it, blood transfusions are helpful, and the doctor may recommend erythropoietin (Aranesp, Eprex, or Neorecormon).

These medications are very well supported, but taking too much should be avoided.

They allow reaching a hemoglobin of 12 g / l but in excess they tend to increase the risk of thrombosis.

The lack of white blood cells is treated with growth factors called Neupogen, Neulasta, or Granocyte.

These growth factors can be responsible for bone pain.

Myeloma is responsible for infections that can be serious mainly due to poor production of good immunoglobulins.

Treatments aggravate this state of immunosuppression.

It is for these reasons that your doctors will insist that you consult quickly in case the temperature rises.

Treatments to prevent infection are:

  • The use of polyvalent immunoglobulins, either by intravenous or subcutaneous infusion.
  • “Preventive” antibiotics like amoxicillin or bactrim to prevent certain forms of pneumonia.
  • Antivirals to prevent shingles or chickenpox.
  • Vaccines, including those for seasonal flu and pneumococcal pneumonia.
  • Application of the growth factors of the white blood cells in case of lack of these cells.

During the active phase of treatment, there is an increased risk of especially venous thrombosis which is usually characterized by painful swelling of one leg.

To prevent this risk, a small dose of aspirin or a subcutaneous injection of heparin (Clexane, Fraxiparin, Innohep) will be prescribed.

The progressive loss of sensation in the feet or hands that reflects the onset of polyneuritis will warrant adaptation of treatment.