Generality
Monoclonal gammopathy is a non-cancerous condition, marked by the accumulation, in the bone marrow and in the blood, of an abnormal protein known as paraprotein (or monoclonal protein or M protein).
From causes that are still uncertain and very often asymptomatic, monoclonal gammopathy can develop, in some rare cases, into very serious malignancies, such as multiple myeloma or lymphoma.
Some blood tests are sufficient to identify monoclonal gammopathy; nevertheless, many doctors prefer to investigate the situation further with further tests.
Until the condition remains asymptomatic, no treatment is expected.
In fact, the only medical indication is to periodically monitor the progress of the condition by appropriate blood analysis.
Brief reference to the bone marrow and its functions
Bone marrow is a soft tissue, present in the internal cavity of some bones (femur, humerus, vertebrae, etc.). Its job is to produce blood cells, ie red blood cells (or erythrocytes ), white blood cells (or leukocytes ) and platelets (or thrombocytes ).
This process is called hematopoiesis (or hematopoiesis ) and starts from particular cells, known as hematopoietic stem cells . The latter are real progenitor cells, able to replicate continuously and to meet different destinies, becoming:
- Red blood cells: they carry oxygen to the tissues and organs of the body.
- White blood cells: they are part of the immune system and defend the body from pathogens and from what can harm you.
- Platelets: they are among the main actors of coagulation.
Figure: hematopoiesis starting from totipotent stem cells. From these derive different types of stem cells, including hematopoietic ones. Hematopoietic stem cells have the gift of continually replicating and of choosing whether to become red blood cells, white blood cells or platelets. From the site: www.liceotorricelli.it
Note: "emato" and "emo" mean "blood", while "poiesi" comes from the Greek verb "poieo" which means "to do" or "to produce".
What is monoclonal gammopathy?
Monoclonal gammopathy, or monoclonal gammopathy of uncertain significance, is a particular health condition, characterized by the accumulation in the bone marrow and blood of an abnormal protein called in various ways: paraprotein, monoclonal protein or M protein .
It is not a form of malignant tumor; however, according to numerous clinical cases, it can be the prelude to different forms of cancer of the immune system or blood cells.
What is the immune system?
The immune system is an organism's defensive barrier against threats from the external environment, such as viruses, bacteria or parasites, but also from within, such as tumoral or malfunctioning cells.
As a whole, the immune system represents a complex integrated network that collects chemical organs, cells and mediators .
Located in various parts of the body, the organs of the immune system (or immune organs) are: bone marrow, spleen, lymph nodes, tonsils and appendix .
Immune cells are the aforementioned white blood cells or leukocytes . There are numerous subpopulations of leukocytes: eosinophils, basophils / mast cells, neutrophils, monocytes / macrophages, lymphocytes / plasma cells and dendritic cells.
Finally, immune chemical mediators are signaling molecules that, by interacting with the various cells of the immune system, exchange information and regulate the level of defensive activity. In other words, they coordinate immune responses.
Causes
Monoclonal gammopathy appears when some plasma cells, located in the bone marrow, undergo an alteration that causes them to produce large quantities of monoclonal protein.
By accumulating, paraprotein takes up space from other (healthy) cells in the bone marrow and also concentrates in the blood.
WHAT ARE THE PLASMA CELLS?
Lymphocytes are the leukocyte subpopulation assigned to acquired (or adaptive or specific ) immunity . The term acquired immunity refers to the ability of the immune system to selectively respond, through hyperspecialized cells (the lymphocytes in fact), to every foreign substance (called antigen ) that attacks the organism.
There are three different types of lymphocytes: B lymphocytes, T lymphocytes and natural killer lymphocytes .
Plasma cells are B lymphocytes which, after contact with a certain class of antigens, have evolved and specialized in countering this class of antigens. The immunology books also call them activated B lymphocytes .
The defensive action of plasma cells is based on the production of particular glycoproteins, known as immunoglobulins or antibodies . Since it is a highly specialized and selective defensive action, each plasma cell produces all the same immunoglobulins, all of which are responsible for fighting only the antigen that activated the B lymphocyte in the plasma cell.
A plasma cell with its antibodies
Immunoglobulins possess a conformation that is very similar to the Greek letter gamma ( γ ): for this reason they are also called gamma globulins . Once produced by plasma cells, they do not directly destroy the antigen they have to counteract, but they bind to it and make it visible and more susceptible to the action of other cells of the immune system (phagocytes and cytotoxic cells). In other words, the antibodies act as signalers: they mark the foreign substance so that other immune cells can recognize and destroy it.
WHAT CHANGES THE ALTERNATION OF THE PLASMA CELLS?
Currently, doctors and researchers have not yet clarified, precisely, what exactly alters plasma cells and induces them and produces an abnormal protein.
Some research has shown that the onset of monoclonal gammopathy is associated with some infections and some autoimmune diseases, such as rheumatoid arthritis.
Please note: anyone suffering from an autoimmune disease has an immune system that acts improperly. In fact, through its innumerable cells, it attacks and damages healthy tissues and organs.
EPIDEMIOLOGY AND RISK FACTORS
Monoclonal gammopathy is considered a rather rare condition; however, there is no more precise information relating to its exact spread in the general population.
Regarding risk factors, several studies have found that monoclonal gammopathy affects the most:
- The elderly, particularly those over 85 years of age. It seems that advanced age is one of the most important predisposing factors.
- Black people . Thus, it seems that the breed plays a certain role.
- Male subjects .
- Individuals with a family history of this disease . From this it was hypothesized that some cases of monoclonal gammopathy could be due to an alteration of the genome, transmitted by inheritance.
Symptoms and Complications
Many patients with monoclonal gammopathy do not experience any symptoms or particular signs, so that often the aforementioned condition is diagnosed by chance, during blood tests prescribed for other reasons.
When symptomatic, monoclonal gammopathy is distinguished by the presence of neurological problems, such as numbness and tingling in the hands and / or feet.
The cause of these neurological disorders is damage to peripheral nerves, which is most likely caused by paraprotein in the blood. Indeed, it appears that the monoclonal protein, when it flows through the blood vessels that nourish peripheral nerves, favors the deterioration of the latter.
In medicine, the morbid condition that develops following damage to peripheral nerves is called peripheral neuropathy .
COMPLICATIONS
In some unfortunate circumstances, monoclonal gammopathy may develop into a true disease, such as multiple myeloma or lymphoma .
Typical symptoms of multiple myeloma
- Bone pains (particularly in the spine, pelvis, ribs, long bones and skull)
- Hypercalcemia. It causes excessive thirst, nausea, constipation, loss of appetite and mental confusion
- Kidney failure
- Anemia. Causes asthenia, generalized weakness and breathing difficulties
- Ease to infections
- Thrombocytopenia
- Hyperviscosity syndrome
- Neurological disorders, including numbness, various nerve compression syndromes, etc.
Multiple myeloma is a malignant tumor specific to the immune system, characterized by such high levels of paraprotein, that problems arise in the kidney and beyond. In fact, those suffering from this severe neoplasm also develop: bone pain (affecting 70% of patients and the most common symptom), hypercalcemia, anemia, coagulation disorders (thrombocytopenia) and immune system deficiency (leukopenia).
Lymphomas, on the other hand, are malignant tumors that affect the lympho-glandular system constituting the lymphatic system. The lymphatic system covers various functions: it accepts (to then eliminate them) the waste substances present in the tissues, houses some cells of the immune system (B lymphocytes and T lymphocytes), prevents the tissues from accumulating excess fluids, etc.
In addition to multiple myeloma and lymphomas, monoclonal gammopathy can also cause recurrent fractures and blood clots that can affect blood circulation (thromboembolism).
How can we tell if a person with monoclonal gammopathy is at risk of multiple myeloma or lymphoma?
According to the doctors, to determine whether an individual with monoclonal gammopathy is more or less at risk of complications, the following parameters must be evaluated:
- The amount of paraprotein in the blood . Very high levels of M protein are very dangerous.
- The type of paraprotein present . Paraprotein does not always have the same characteristics in all patients. It appears that some types of monoclonal protein are more harmful than others.
- The amount in the blood of "free" light chains (also called Bence Jones proteins) . The immunoglobulins consist substantially of two parts joined together: light chains and heavy chains. In an individual with monoclonal gammopathy, due to an abnormal behavior of plasma cells, light chains are not linked to heavy chains and can be found in the blood. If they are particularly high, multiple myeloma may be suspected.
WHEN TO REFER TO THE DOCTOR?
It is advisable that a person with monoclonal gammopathy, up to that moment asymptomatic, contact your doctor immediately if:
- He feels extreme and unusual tiredness.
- It tends easily to breathlessness, even on the occasion of very simple activities.
- He suffers from pains in the bones constant and localized in precise points (for example at the level of the back, hips, ribs or pelvis).
- Inexplicably loses weight.
- It is particularly prone to infections. This is a clear sign of an immune problem linked to the lack of leukocytes.
Diagnosis
To correctly diagnose monoclonal gammopathy, two blood tests (blood chemistry tests ) may be sufficient, called seroprotein electrophoresis (or serum protein electrophoresis) and immunoelectrophoresis.
The use of further tests (urine tests, other blood tests, X-rays, CT scans and bone marrow biopsy) serves above all to assess the severity of the anomaly and the risk of complications.
Moreover, a very accurate diagnostic procedure allows the identification of multiple myeloma or lymphoma.
SERIO-PROTEIN ELECTROPHORESIS AND IMMUNOELECTROPHORESIS
The electrophoresis of serum proteins allows to evaluate the quantitative levels of 5 serum proteins: albumin and α1, α2, β and γ globulins. In patients with monoclonal gammopathy, these 5 serum proteins show characteristic alterations, which a hematologist (a doctor experienced in the diagnosis and treatment of blood diseases) is able to recognize.
FURTHER EMATOCHIMICAL EXAMINATIONS
To investigate the situation, doctors use other blood tests, including:- Blood count . It is used for an assessment (quantitative and not only) of red blood cells, white blood cells and platelets. It is useful in case of suspected lymphoma or multiple myeloma, because it allows to identify possible states of thrombocytopenia, neutropenia (decrease in neutrophil leukocyte blood) etc.
- Creatinine measurement . Blood creatinine levels are an index of renal activity. If they are elevated, it means that the kidneys are malfunctioning. Remember that multiple myeloma affects kidney function, therefore, in these situations, creatinine is generally very high.
- Measurement of serum calcium . The finding of large amounts of calcium in the blood could mean multiple myeloma.
URINALYSIS
In people with monoclonal gammopathy and multiple myeloma, urine contains Bence Jones proteins (in the second case, "free" light chain levels are also very high).
Therefore, their examination serves as a further confirmation of what has already been observed with protein serum electrophoresis and immunoelectrophoresis.
X-RAY
X-rays are useful in cases of suspected multiple myeloma, since this serious malignant tumor also involves the skeletal structure, resulting in bone anomalies (also called rearrangements).
TAC
CT (or computerized axial tomography ) is a method that uses ionizing radiation to construct a highly detailed three-dimensional image of a given body compartment. It is completely painless, but the X-ray dose to which patients are exposed is not negligible.
In the case of monoclonal gammopathy, it is practiced to assess the dimensional aspect of lymph nodes, liver and spleen.
In some cases, to improve the quality of the images, doctors could use a contrast liquid (gadolinium), which is injected into the blood and is not free from possible side effects.
BIOPSY OF BONE MARROW
A biopsy consists of the collection and histological analysis, in the laboratory, of a sample of cells from a certain tissue or organ.
On the occasion of a bone marrow biopsy, the collection of the cells to be analyzed takes place at the level of the iliac crests, using a special needle and after local anesthesia.
Subsequent laboratory analyzes are used to quantify the number of plasma cells (and paraprotein) present in the bone marrow.
At the end of the procedure, at the insertion point of the needle, the patient could develop a small hematoma.
Warning: doctors perform a bone marrow biopsy only when they consider the presence of multiple myeloma highly probable.
Treatment
Until the monoclonal gammopathy is asymptomatic (most cases), no particular therapeutic treatment is foreseen . The only indication, which doctors provide in these situations, is to regularly monitor the situation, undergoing blood tests described in the previous chapter (seroprotein electrophoresis, immunoelectrophoresis, blood count, etc.) every 4-6 months.
If care is taken to act in the aforementioned manner, careful surveillance is carried out, which ensures that any worsening of monoclonal gammopathy or its evolution towards some form of malignant blood cell tumor is detected in time.
WHEN MONOCLONAL GAMMOPATHY BECOMES MULTIPLE MYELOMA
If unfortunately the monoclonal gammopathy should develop into multiple myeloma, it is appropriate to start immediately, without unnecessary waiting, a therapy appropriate to the malignant tumor.
Patients under 65 years of age are generally treated with chemotherapy, corticosteroid drugs and hematopoietic stem cell transplantation . The latter, for reasons related to the availability of adequate donors, is more frequently autologous than allogeneic. However, it is worth pointing out that allogeneic transplantation has a greater therapeutic potential.
Patients over the age of 65, on the other hand, are generally treated only with chemotherapy and corticosteroids (prednisone), as haematopoietic stem cell transplantation (whether autologous or allogeneic) is a contraindicated health practice (NB: they could do not hold the procedure and develop serious complications).
Chemotherapy drugs prescribed for multiple myeloma
For patients under 65:
- Thalidomide
- Bortezomib
- Lenalidomide
For patients over 65:
- melphalan
- Bortezomib
OTHER TYPES OF TREATMENT
If patients suffer from recurrent bone fractures, a bisphosphonate treatment is provided which serves to strengthen the bones (to be precise, they reduce bone resorption and increase bone mineral density).
Among the bisphosphonates, those most commonly administered in the case of monoclonal gammopathy are: zoledronic acid, alendronic acid (alendronate), risedronate and ibandronic acid.
SOME ADVICES
For people with monoclonal gammopathy, hematologists strongly recommend:
- Inquire about everything concerning the condition that afflicts them. Knowing the possible symptoms, complications and diagnostic surveillance tests allows better control of any change / evolution of monoclonal gammopathy.
On the contrary, neglecting the aforementioned aspects or knowing them only superficially could be very dangerous.
- Adopt a healthy lifestyle. Eating fruits and vegetables, not smoking, exercising regularly and sleeping the right number of hours are behaviors that do not reduce the risk of complications, but make the onset of other diseases (comorbidities) less likely.
- Follow the check exams calendar scrupulously. The mistake some patient may make is to neglect the checks, because the latter, for some time, have given negative results.
Prevention
Monoclonal gammopathy is a condition that cannot be prevented, as its precise triggering causes are not known.
The same goes for his complications: since the reasons leading to the latter are not known, it is impossible to implement adequate preventive measures.
Prognosis
As long as it remains asymptomatic, monoclonal gammopathy has a non-negative prognosis.
However, it must be considered that the bearer must consider himself a person at risk of cancer and must therefore remain constantly monitored.
All this, therefore, could in some way affect daily life.
As far as the complications induced by monoclonal gammopathy are concerned, their diagnosis takes place first and the possibilities for treatment are greater.
