Multiple myeloma: predisposing factors, symptoms, diagnosis, treatment

Multiple myeloma is a type of blood cancer, although the main manifestations of this disease are associated with bone damage. The basis of the disease is damage to a certain type of leukocyte (plasmocyte). Like all other blood cells, plasma cells are formed from stem cells in the bone marrow. The formation process is a series of successive divisions in which lymphoid stem cells are formed first, and then B lymphocytes.

B lymphocytes are immune cells that fight bacteria and viruses that are foreign to the body. These cells finally mature outside the bone marrow: in the thymus, spleen and lymph nodes. To do this, they need an antigen, which is a protein of a foreign microorganism. Contacting such an antigen, the B lymphocyte becomes a plasma cell, beginning to secrete antibodies - special proteins that can destroy foreign cells. Each plasma cell is capable of secreting a specific type of antibody aimed at fighting a specific microorganism. During normal functioning of the body, a person produces a certain and strictly controlled number of plasma cells.

Causes of multiple myeloma

In myeloma, the DNA of plasma cells is damaged. Because of this, an excessive number of altered and useless plasma cells (they are also called myelocytes) accumulate in the body. Such cells accumulate in the bones, causing tumors, destroying bones and producing defective proteins (also called Bence Jones proteins, monoclonal). Such proteins, unlike normal antibodies, cannot fight foreign cells; they are excreted from the body by the kidneys.

When bones are destroyed, the level of calcium in the patient's blood increases: this is evidenced by frequent constipation, nausea and thirst. If the amount of protein and calcium in the body is increased, it leads to kidney damage. Moreover, normal hematopoiesis in the body is disrupted, due to which the number of normal leukocytes and red blood cells decreases. As a result, a person develops anemia, and the body's resistance to infections decreases.

Although the exact cause of the onset of pathological changes in plasma cells is still unknown, there are certain factors that can increase the likelihood of developing multiple myeloma.

In children

Cases of multiple myeloma in children are considered rare, since it is 140 times less common in childhood. Diagnosis of this disease in children is difficult due to its rare occurrence at this age and the reduced alertness of doctors. The diagnosis is made by detecting myeloma cells in the bone marrow and a typical x-ray picture. The clinical picture does not differ from that in adults, but in children the lymph nodes are more often involved, which is associated with the generalization of the process. The course of the disease in children is steadily progressive. Average life expectancy is 2-3 years.

Symptoms of multiple myeloma

Symptoms of myeloma directly depend on the activity of the process; often in the initial stages of the disease they are completely absent. The signs themselves are nonspecific - that is, the appearance of certain symptoms can be provoked by a completely different disease. That is why only a doctor can determine the exact cause of their appearance.

The main symptoms of myeloma are:

• thirst;
• constipation;
• frequent infections;
• frequent fractures;
• bone pain (usually in the vertebrae, ribs);
• malaise and weakness;
• pain, numbness of the limbs;
• increase or decrease in urine volume;
• frequent urination.

List of sources

• Mendeleeva L.P., Votyakova O.M., Rekhtina I.G. Multiple myeloma. Russian clinical guidelines for the diagnosis and treatment of malignant lymphoproliferative diseases. Ed. I.V. Poddubnoy, V. G. Savchenko. M., 2021. P.: 213–41.
• Bessmeltsev S.S. Multiple myeloma (pathogenesis, clinical picture, diagnosis, differential diagnosis) // Clinical oncohematology. — 2013.— T6, No. 3.— P. 237-257.
• Bessmeltsev S.S., Abdukadyrov K.M. Multiple myeloma. A modern view of the problem. Almaty, 2007.
• Moiseev S.I., Salogub G.N., Stepanova N.V. Modern principles of diagnosis and treatment of multiple myeloma. – St. Petersburg: St. Petersburg State Medical University Publishing House, 2006. – 39 p.
• Votyakova O.M. Multiple myeloma: achievements of drug treatment of the XXXXI centuries // Oncohematology. – 2004. – T. 6, No. 4 – P. 1925.

Who is at risk for multiple myeloma?

• People over 60 years of age;
• People suffering from obesity;
• People who have been exposed to radiation;
• People who worked with pesticides, insecticides, petroleum products, and other toxic substances;
• People whose relatives suffered from multiple myeloma;
• Patients suffering from HIV infection;
• Patients suffering from monoclonal gammopathy (a group of diseases in which the human body begins to produce
• abnormal antibodies);
• Patients suffering from autoimmune diseases (for example, systemic lupus erythematosus or rheumatoid arthritis).

Diet

Diet 15 table

• Efficacy: therapeutic effect after 2 weeks
• Timing: constantly
• Cost of food: 1600-1800 rubles per week

Nutrition for this disease must be complete in essential nutrients and have sufficient energy value. Complete protein in sufficient quantities is important in the diet (beef, poultry, rabbit, turkey, liver, fish, cottage cheese). The patient should receive 2 grams of protein per kilogram of weight daily.

Steamed meatballs, meatballs or cutlets are prepared from meat products. Sources of calcium include fermented milk products, cottage cheese, sunflower and sesame seeds. The daily diet should include foods containing vitamins B and C, and, taking into account anemia, foods rich in iron (beef, beef liver, pomegranate). Meals should be fractional - small portions for better digestion and to avoid digestive overload.

Simple carbohydrates are excluded, since taking dexamethasone and prednisolone may increase sugar levels. You should not eat fatty, fried and spicy foods, fatty milk and cream, rich soups, smoked foods, canned food and pickles. During the period of remission, nutrition can be more varied and strict restrictions are not provided. Vitamins and microelements are still important in the diet, the sources of which are green vegetables, fruits, flaxseed and olive oil, fish oil, and a variety of nuts.

Diagnosis of multiple myeloma

In many cases, multiple myeloma is detected even before its main symptoms appear, during a standard preventive examination. Changes observed in the results of laboratory tests allow specialists to suspect this disease in a patient at an early stage. Further examination directly depends on the manifestations of the disease.

Laboratory tests necessary to diagnose multiple myeloma:

• Clinical blood test. As a rule, with multiple myeloma, the level of white blood cells in the body is reduced. Similarly, the level of hemoglobin, platelets and red blood cells may be reduced;
• Proteinuria (excretion of Bence Jones protein in the urine);
• Total whey protein: due to the large amount of monoclonal proteins, its level increases;
• Serum albumin. Albumin is a protein synthesized in the liver that is responsible for the transport of various substances - for example, certain hormones, fatty acids and bilirubin. Its level can decrease even with high total protein, since normal protein increases precisely due to the presence of pathological components - monoclonal proteins similar in structure to albumin;
• Serum creatinine is a metabolic byproduct that is excreted through the kidneys. In multiple myeloma, the kidneys are damaged, which can cause creatinine to be elevated.

Multiple myeloma is a malignant blood disease in which an excessive number of defective plasma cells (one of the types of white blood cells) are formed, which leads to damage to the bone marrow, bones, kidneys, and disruption of the immune system.

Damaged plasma cells can form tumors, which are usually located in the bones. If there is only one tumor, it is called a solitary plasmacytoma. If there are several tumors, we are talking about multiple myeloma.

Myeloma is a fairly rare disease that most often affects people over 60 years of age. Patients under 40 years of age are extremely rare. This disease is incurable, but modern treatment methods make it possible to stop the development of the process for several years. The prognosis of the disease largely depends on the stage at which treatment is started.

Synonyms Russian

Rustitsky's disease, myeloma, myelomatosis, reticuloplasmocytosis, generalized plasmacytoma, Rustitsky-Kahler disease.

English synonyms

Plasma cell myeloma, Kahler's disease, myeloma.

Symptoms

Manifestations of myeloma depend on the activity of the process, and at the initial stage the disease may be completely absent. Signs of myeloma are nonspecific, that is, the same symptoms can be caused by another disease, so only a doctor can determine the exact cause of their appearance. The main symptoms are:

• pain in the bones, often in the ribs, vertebrae,
• frequent fractures,
• frequent infectious diseases,
• weakness, malaise,
• thirst,
• constipation,
• frequent urination,
• increase or decrease in urine volume,
• numbness, pain in the limbs.

General information about the disease

Despite the fact that the main manifestations of the disease are associated with bone damage, myeloma is a type of blood cancer. The disease is caused by damage to plasma cells, a type of white blood cell. They, like all other blood cells, are formed in the bone marrow from stem cells. This process consists of a series of sequential cell divisions programmed at the DNA level, as a result of which lymphoid stem cells are first formed, and then B lymphocytes. B lymphocytes are immune cells, that is, they fight viruses and bacteria foreign to the body. The final maturation of B lymphocytes occurs outside the bone marrow - in the lymph nodes, spleen, and thymus. This requires an antigen - a protein of a foreign microorganism. Upon contact with an antigen, the B lymphocyte turns into a plasma cell and begins to secrete antibodies - specific proteins that destroy foreign cells. Each plasma cell secretes a specific type of antibody aimed at combating a specific microorganism. Normally, a person produces the necessary, strictly controlled number of plasma cells.

In multiple myeloma, the DNA of plasma cells is damaged. The body accumulates an excessive number of useless, altered plasma cells, which are also called myelocytes. These cells accumulate in the bones, forming tumors and destroying bones, and also produce defective proteins - monoclonal proteins, or Bence Jones proteins. These proteins are not able to fight foreign cells like normal antibodies and are excreted from the body by the kidneys. Bone destruction leads to an increase in calcium levels in the blood, which is manifested by thirst, constipation, and nausea. Elevated amounts of calcium and protein cause kidney damage. Normal hematopoiesis is inhibited and, as a result, the number of red blood cells and normal leukocytes decreases. As a result, anemia develops and the body's resistance to infections decreases.

The exact cause of pathological changes in plasma cells is unknown, but there are factors that increase the likelihood of multiple myeloma.

Who is at risk?

• People over 60 years of age.
• Obese people.
• Those exposed to radiation.
• Working with insecticides, pesticides, petroleum products and other toxic substances.
• HIV-infected.
• Patients with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus.
• Patients with monoclonal gammopathy (a group of diseases in which the body produces abnormal antibodies).
• People whose relatives had myeloma.

Diagnostics

Often multiple myeloma is detected before symptoms appear, during a standard preventive examination. Changes in the results of laboratory tests allow you to suspect the disease at the initial stage. Further examination depends on the manifestations of the disease.

Laboratory diagnostics

• Complete blood count (without leukocyte formula and ESR). In multiple myeloma, the level of leukocytes is most often reduced. Concentrations of red blood cells, platelets and hemoglobin may also be reduced.
• Proteinuria is determined, that is, the excretion of Bence Jones protein in the urine.
• Total whey protein. Its level is increased due to a large number of monoclonal proteins.
• Serum albumin. Albumin is a protein that is synthesized in the liver and is responsible for the transport of various substances, such as bilirubin, fatty acids, and some hormones. The level of albumin can be reduced even with a high total protein, since the protein is increased precisely because of pathological components - monoclonal proteins, which differ in structure from albumin.
• Serum creatinine. It is a metabolic by-product that is excreted by the kidneys. In multiple myeloma, it may be elevated due to kidney damage.
• Serum calcium. Calcium levels rise due to bone breakdown.

Other research methods

• Electrophoresis of urine and blood proteins. The method is necessary for the detection of monoclonal proteins and Bence Jones proteins. It is based on the fact that different types of proteins placed on a special paper, gel or membrane move at different speeds under the influence of a constant electric field.
• Bone marrow biopsy is the removal of a sample of bone marrow from the breastbone or pelvis using a fine needle. It is carried out after preliminary anesthesia. Changes in the structure of the bone marrow are then detected under a microscope. The procedure is necessary to identify plasma cells in the bone marrow.
• X-ray, computed tomography and magnetic resonance imaging. These methods make it possible to take photographs of bones, which identify clearly defined, round or oval-shaped areas of bone destruction, as well as pathological fractures.

• Positron emission tomography. Deoxyfluoroglucose, a drug labeled with a radionuclide, is injected into the body, which is absorbed by tumor cells. Then, using a positron camera, areas of accumulation of this substance are examined. Deoxyfluoroglucose remains in the body for a very short time; most of it disintegrates during the study, which reduces the radiation dose to the patient. The information value of the method lies in the fact that it is possible to evaluate not only the external characteristics of the tumor, as with CT or MRI, but also the metabolic activity in the tumor tissues.

Treatment

Treatment depends on the stage of the disease, the type of myeloma, and the general condition of the patient. At the initial stage, before the appearance of external signs and with slow progression of the disease, treatment may be delayed. However, the patient should undergo regular examinations to monitor the progression of the disease. Treatment should be started at the first symptoms.

• Chemotherapy is the use of special drugs that destroy malignant cells or prevent them from dividing.
• Immunotherapy. When treating multiple myeloma, drugs that activate the immune system are used. The structure of these drugs is identical to substances that are produced by leukocytes and are involved in the fight against infections and cancer cells. Most often, synthetic interferon alpha is used - a specific protein that is identical in structure to human interferon and has antiviral activity.
• Radiation therapy is the destruction of malignant cells using ionizing radiation.
• Stem cell transplantation. A portion of the stem cells is taken from a patient with multiple myeloma or a suitable donor using a special device, after which they are frozen. The patient then undergoes chemotherapy or radiation therapy, which destroys most of the bone marrow cells, both sick and healthy. After this, the patient is transplanted with his own or donor stem cells. Stem cell transplantation does not cure the patient, but it increases his life expectancy.
• Symptomatic therapy is therapy aimed at specific symptoms. For example, antibiotics for infection and administration of erythropoietin (a substance that stimulates the division of red blood cells) for anemia.

Prevention

There is no specific prevention of multiple myeloma.

Recommended tests

• General blood analysis
• General urine analysis with microscopy
• Serum calcium
• Serum creatinine
• Total protein in whey
• Serum albumin
• Cytological examination of punctates, scrapings of other organs and tissues

Reviews of patients with multiple myeloma cured in Israel

Evgenia, 54 years old, Moscow

“There was pain in the hip joint. Local doctors prescribed medications, but did not perform the operation because they were not sure of the diagnosis. My condition began to worsen, so I had to consider the option of treatment abroad. I chose Israel; the Soroka clinic was the right price for me. I arrived at the clinic and underwent examination. Doctors diagnosed myeloma in the hip bone and several other lesions in other bones. A treatment program was immediately developed for me, which I successfully completed. The disease is now in remission. We’ll see what happens next, but at the moment I am completely satisfied with the result of the treatment and the attentive attitude of the Israeli doctors.”

To prevent myeloma from breaking

Oncohematologists and psychologists advise patients to treat their disease not as incurable, but as chronic. Myeloma requires constant monitoring and treatment, but you can live with this disease. In principle, in this regard, this formidable pathology is not much different from hypertension, coronary heart disease, diabetes mellitus, rheumatological diseases and other chronic diseases characterized by constant periods of exacerbation and remission. And yet, there is no need to put your illness in first place, where by right every person should have his own life with its interests and joys, goals and achievements. This attitude will definitely help you cope with any difficulties!

Stages and prognosis for multiple myeloma

Staging of multiple myeloma is determined based on 4 parameters: the amount of M component, hemoglobin level, calcium level, and the degree of bone damage. Stages:

• Stage 1 myeloma - mild anemia (hemoglobin more than 100 g/l), normal calcium, low M-protein, less than 5 bone lesions. The average life expectancy of such patients is 6.5 years.
• Stage 2 of myeloma - moderate anemia, calcium increased to 3 mmol/l, the number of osteolysis foci does not exceed 20, M-component level: 35 IgG < 35-70 g/l IgM 30-50, Bence-Jones proteinuria 4-12 g /day.
• The third stage of myeloma is diagnosed in the presence of at least one of the following signs - severe anemia (hemoglobin below 85 g/l), calcium above 3 mmol/l, high level of M-protein, severe osteodestruction (more than 30 foci of osteolysis - bone destruction). The average life expectancy is 2 years.

In addition, there is a myeloma staging system based on the level of B2-microglobulin and albumin in the blood:

• Stage 1 of multiple myeloma - B2-microglobulin below 3.5 mg/l, albumin above 35 g/l.
• Stage 2 myeloma - B2-microglobulin increases to 5.5 mg/l, albumin decreases below 35 g/l.
• Stage 3 myeloma - B2-microglobulin values ​​exceed 5.5 mg/l.

Treatment

The selection of drugs for myeloma and the treatment method are selected depending on the stage of the disease. Active therapy is prescribed when the disease develops intensively and the tumors increase in size. Prescribed:

• bone marrow transplant. This is the most effective way to cure this disease;
• chemotherapy - taking drugs that quickly rid the body of abnormal cells. The result of this method is assessed no earlier than after 3 months;
• local radiation therapy. In this case, certain parts of the patient's body are irradiated. The method is effective when tumor nodes are limited. It should be understood that in the irradiated area the probability of disease recurrence increases 5 times;
• restoration of normal mineral and protein metabolism. For this purpose, calcium, vitamin D, and steroids are used;
• correction of renal failure, restoration of normal renal function;
• surgical techniques (according to indications);
• extracorporeal techniques, the essence of which is blood purification with special devices (hemodialysis, plasmapheresis, hemosorption);
• transfusion of red blood cells (necessary for anemia, including those accompanied by a coma);
• physiotherapy;
• taking immunomodulatory drugs.

Paradigm Shift

Every year in Russia, myeloma is diagnosed in 4.5 thousand people (counting only new cases of the disease). For most patients, encountering a diagnosis comes as a huge shock, because it soon becomes clear that this is an incurable disease. And that even despite the most modern and timely treatment, sooner or later you will inevitably have to face a relapse of the disease. Therefore, according to psychologists, 30-35% of people with this diagnosis suffer from depression and anxiety disorders. Over time, this number becomes even higher, since the drugs used to treat MM themselves can increase the risk of depression. Therefore, in addition to oncohematologists, psychotherapists often take part in treatment.

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However, today an unprecedented breakthrough has occurred in oncohematology. And in particular, people with multiple myeloma, who until recently were doomed to quick death (even with the disease detected at an early stage, patients lived only a few years), today, thanks to innovative biologically targeted drug therapy, they can live quite a long and high-quality life. Just 7 years ago, the 5-year disease-free survival rate for MM was 36%, and today it reaches 50%.

Types of multiple myeloma

There are several classifications of myeloma. According to the degree of prevalence of tumor lesions, they are distinguished:

• Diffuse form of multiple myeloma. Bone marrow infiltration occurs without bone destruction (osteodestruction).
• Diffuse focal form of myeloma. In addition to bone marrow infiltration, there are foci of bone destruction.
• Multiple focal form of myeloma. There are foci of osteodestruction, but there is no diffuse damage to the bone marrow. In this case, when examining the punctate, it is possible to obtain a normal myelogram.
• Rare forms of myeloma - sclerotic, visceral, etc.

Multiple myeloma is also classified based on the immunochemical type of the tumor. The main factor here is the type of pathological immunoglobulin detected in the blood and urine. There are G, A, D, E, M-myeloma, Bence Jones myeloma, biclonal and non-secreting.

How is multiple myeloma treated?

Multiple myeloma is now considered an incurable disease. Medical efforts are aimed at containing tumor growth, prolonging and improving the quality of life of such patients.

After the diagnosis has been established, it is necessary to decide whether the patient needs specific treatment, or whether observation can be limited, since with “smoldering myeloma” (there are no symptoms, but there are laboratory changes), a wait-and-see approach is possible.

The following types of treatment for myeloma are distinguished:

• Standard chemotherapy. Prescribed to patients for whom high-dose chemotherapy is contraindicated. The average life expectancy after it is 29 months. The standard first-line regimen includes melphalan and prednisolone. More effective regimens include thalidomide, lenalidomide, or bortezomib (relatively new anticancer drugs).
• High-dose polychemotherapy (HDPT) followed by transplantation of hematopoietic stem cells HSCT (both autologous and donor). This treatment allows to achieve complete remission in most patients (up to 75%), but unfortunately, progression of the disease is observed within 2-5 years. It is more effective to conduct a double course of HPCT with HSCT (tandem HPCT). It allows achieving five-year disease-free survival in 90% of patients. But not all patients can tolerate such severe treatment, so indications for it are limited.
• Maintenance therapy. Even VHD cannot prevent the development of relapse; treatment is prescribed, which is designed to suppress the clone of malignant cells. Interferons are used for this purpose. They help extend the median disease-free survival to 42 months.
• Combating complications. Pain treatment is the prescription of strong analgesic drugs, radiation therapy. Surgical operations are performed for compression fractures of the vertebrae. Correction of complications caused by inhibition of hematopoiesis - transfusion of red blood cells and administration of erythropoietin, use of antibiotics for fever. Carrying out hemodialysis, plasmapheresis, prescribing bisphosphonates to control hypercalcemia.