Shows m gradient. Screening for multiple myeloma and paraproteinemias (immunofixation of blood serum with pentavalent serum)

On the eve of the study, consumables (a container with an adapter and a test tube) must first be obtained from any laboratory department.
Please note that in the laboratory department is supplied with biomaterial only in a urine tube with an olive cap (according to the instructions for taking).

Bence Jones protein- a tumor marker that is used to diagnose multiple myeloma (plasma cell tumors). Bence-Jones protein consists of free light chains of immunoglobulins. At healthy people not a large number of free light chains are produced continuously, along with complete immunoglobulin molecules. Due to their small molecular weight and neutral charge, they are filtered into the primary urine through the glomerular basement membrane, then reabsorbed and metabolized in the proximal tubule without entering the final urine. In monoclonal gammopathy, there is production of abnormal immunoglobulins by a malignant clone of plasma cells. This results in an excess of free light chains in the primary urine and Bence-Jones protein in the final urine.

The synthesis of monoclonal immunoglobulins is accompanied by the formation of a variable amount of light chains. About 20% of myeloma cases are characterized by the production of exclusively monoclonal light chains (light chain disease).

The determination of Bence-Jones protein in urine reflects kidney damage - tubular atrophy, pronounced sclerosis of the interstitium of the kidney. Damage is exacerbated by predisposing factors (dehydration, hypercalcemia, the use of radiopaque agents, some medicines), which can lead to kidney failure.

• Percentage of albumin in urine
• Screening for paraprotein in urine (Bence-Jones protein) with polyvalent antiserum
• M-gradient in urine (Bence-Jones protein), concentration
• Determination of total protein content in urine

Service code: 31.4.3.4051
2895 ₽
M-gradient, typing. Serum electrophoresis, immunofixation with a panel of antisera (separately for IgG, IgA, IgM, kappa, lambda), M-protein quantification

Laboratory diagnostics
: proteins and amino acids.

Indications

• Paraprotein typing.
• Differential diagnosis of monoclonal gammopathy.
• Evaluation of the effectiveness of ongoing therapy for myeloma and other gammopathy

Description
Detection and typing of monoclonal immunoglobulins.
Immunoglobulins are proteins that have antibody activity (the ability to specifically bind certain antigens). Unlike most serum proteins, which are produced in the liver, immunoglobulins are produced by plasma cells, descendants of B-lymphocyte progenitor stem cells in the bone marrow. According to structural and functional differences, 5 classes of immunoglobulins are distinguished - IgG, IgA, IgM, IgD, IgE and a number of subclasses. A polyclonal increase in immunoglobulins is a normal response to infections.

Monoclonal gammapathies are conditions in which a clone of plasma cells or B-lymphocytes (a population of cells originating from a single progenitor B-cell) produces an abnormal amount of immunoglobulin. Such conditions can be benign or be a manifestation of the disease. Monoclonal gammopathy is identified by the appearance of an abnormal protein band on serum or urine electrophoresis.

Immunoglobulin molecules consist of one or more structural units built according to a single principle - from two identical heavy chains and two identical light peptide chains - kappa or lambda. Varieties of heavy chains are the basis for dividing immunoglobulins into classes. Immunoglobulin chains have constant and variable regions, the latter being associated with antigenic specificity.

Immunoglobulin produced by one clone of cells has an identical structure - it represents one class, subclass, is characterized by an identical composition of heavy and light chains. Therefore, if an abnormally large amount of monoclonal immunoglobulin is present in the serum, it migrates in the form of a compact band during the electrophoretic separation of blood serum proteins, which stands out against the background of the standard distribution pattern of serum protein fractions. When describing the results of serum protein electrophoresis, it is also called paraprotein, M-peak, M-component, M-protein or M-gradient. According to the structure, such a monoclonal immunoglobulin can be a polymer, a monomer, or a fragment of an immunoglobulin molecule (in the case of fragments, these are more often light chains, less often heavy). Light chains are able to pass through the renal filter and can be detected by urine electrophoresis.

The detection of monoclonal paraproteins is based on the use of protein electrophoresis. Sometimes fibrinogen and CRP, which migrate into gamma fractions, can be mistakenly regarded as paraproteins. The immunoglobulin nature of the identified monoclonal component is confirmed by immunofixation of the separated proteins with a specific polyvalent precipitating antiserum directed against immunoglobulins (test No. 4050). When confirming the presence of monoclonal immunoglobulin, densitometry is performed and its quantitative content is determined. For a complete identification (typing) of the monoclonal component, a detailed study using electrophoresis and immunofixation with a detailed panel of antisera against IgG, IgA, IgM, kappa and lambda chains is required (test No. 4051). In diagnosis and prognosis, the class of the identified paraprotein, its concentration at the time of diagnosis, and the rate of increase in its concentration over time are taken into account. The presence of paraprotein is a marker of a number of hemato-oncological diseases.

Multiple myeloma is a classic hematological disease caused by malignant proliferation of plasma cells secreting monoclonal immunoglobulin (paraprotein) or its fragments. Plasma cells often proliferate diffusely in the bone marrow, the disease leads to osteolytic bone lesions, reduction of other cells bone marrow, which leads to anemia, thrombocytopenia, leukopenia, inhibits the development of normal clones of plasma cells. Patients may present with local symptoms of bone disease (pain, fractures) or non-specific symptoms (weight loss, anemia, bleeding, repeated infections, or kidney failure). In most patients at the time of diagnosis, the paraprotein concentration exceeds 25 g/l. In myeloma, the paraprotein in the blood serum is most often represented by IgG (60%), less often by IgA (20%), and about 20% are due to Bence-Jones myeloma, associated with the production of free kappa or lambda light chains (20%), which can be found in urine. Sometimes in myeloma, a biclonal paraprotein can be observed, represented by immunoglobulins of different classes or of the same class, but containing light chains of different classes. Rarely marked IgD and IgE myeloma. Determination of paraprotein concentration is used to monitor the effectiveness of myeloma treatment, such monitoring in myeloma during therapy should be carried out every 3 months. If the paraprotein content dropped below the detectable value, remeasurement it is advisable to carry out after 6 or 12 months.

Macroglobulinemia Waldenström is a lymphoma with overproduction of monoclonal IgM. Lymphoplasmacytic tumor cells with a characteristic immunophenotype are diffusely distributed in the lymph nodes, spleen, and bone marrow. A high concentration of monoclonal IgM often exceeds 30 g/l and leads to an increase in blood viscosity and a number of clinical manifestations including confusion, blindness, bleeding tendency, heart failure, and hypertension. With macroglobulinemia, paraproteinemic polyneuropathy, cold hemolytic anemia and cryoglobulins. In other types of lymphomas and chronic lymphocytic leukemia, paraproteins of the IgM class are observed in 20% of patients, but the paraprotein concentration is usually lower than 30 g / l.

Heavy chain disease (Franklin's disease) is accompanied by the synthesis of only the IgG-gamma heavy chain, without an accompanying light chain. This extremely rare disease is manifested by edema of the soft palate and lymphoid infiltration. Also rare is alpha heavy chain disease, which causes chronic diarrhea, malabsorption due to lymphoid infiltration of the intestinal wall.

Monoclonal paraprotein can be found in a number of non-neoplastic diseases, in particular, in essential cryoglobulinemia (usually IgM), paraproteinemic chronic polyneuropathy, cold hemolytic anemia, renal AL amyloidosis (lambda free chains), and internal organs, light chain deposition diseases. Paraprotein in the blood serum is also noted in Castleman's disease (IgM / lambda), POEMS syndrome (polyneuropathy with organ megalia) and myxedematous lichen (IgG / kappa).

In screening examinations, the incidence of paraproteinemia increases sharply in the population after reaching 50 years of age and reaches 4–10% in people over 65 years of age. However, the majority of newly diagnosed paraproteinemias in the general population are asymptomatic monoclonal gammopathy of unknown significance (MGUS). The concentration of paraprotein in MGNS is significantly below 30 g/l and usually does not exceed 10–15 g/l. In addition, with MGNS, the paraprotein is detected against the background of polyclonal immunoglobulins, i.e., there is no inhibition of the normal synthesis of other immunoglobulins. The term "MGNS" refers to cases of paraproteinemia without other signs of hematological malignancy, which require annual monitoring in order not to miss the moment of malignization of the process. If paraproteins are detected in those examined younger than 50 years, even more frequent re-examinations are necessary, since they have a high risk of developing multiple myeloma. If the M-protein concentration is more than 15 g/l, regardless of age, it is recommended to conduct an extended examination, including electrophoresis of a 24-hour urine sample and immunofixation every 3–6 months, since the risk of malignant transformation is very high. Allocate benign paraproteinemia, which is characterized by the preservation of paraprotein without progression to multiple myeloma or other disease within 5 years of follow-up. In transient paraproteinemia, the paraprotein concentration is usually below 3 g/L.

Determination of quantitative and qualitative changes in the main fractions of blood protein, used to diagnose and control the treatment of acute and chronic inflammation infectious and non-infectious genesis, as well as oncological (monoclonal gammopathy) and some other diseases.

With the proliferation of a clone of plasma cells, the synthesis of immunoglobulin is increased, represented by one class, subclass and isotype, which includes heavy and light protein chains of the same type. During electrophoretic separation of blood serum proteins, this immunoglobulin migrates in the form of a compact band, which is determined against the background of other protein fractions. Such an immunoglobulin is called a monoclonal immunoglobulin or a paraprotein. In serum protein electrophoresis, it is called the M-gradient. Paraprotein is a tumor marker in a number of hemato-oncological diseases.

Multiple myeloma is a classic hematological disease that is caused by the proliferation of plasma cells that secrete monoclonal immunoglobulin (paraprotein) or its fragments. In most cases, at the time of diagnosis, the paraprotein concentration exceeds 25 g/l.

With myeloma, the paraprotein in the blood serum is most often represented by IgG (60%), less often by IgA (20%). The remaining about 20% of cases are Bence-Jones myeloma associated with the production of free kappa or lambda light chains (20%). In 2–4% of myeloma cases, a biclonal paraprotein can be observed, represented by immunoglobulins of different classes or the same class, but containing light chains of different classes. Changes in paraprotein concentration serve as an indicator of the effectiveness of myeloma treatment. Monitoring of the concentration of PP in myeloma during therapy should be carried out every 3 months. If the content of PP has decreased below the detectable level, it is advisable to re-measure after 6 or 12 months.

Macroglobulinemia Waldenström is a lymphoma with overproduction of monoclonal IgM. Lymphoplasmacytic tumor cells with a characteristic immunophenotype are diffusely distributed in the lymph nodes, spleen, and bone marrow. A high concentration of monoclonal IgM often exceeds 30 g/l and leads to an increase in blood viscosity and a number of clinical manifestations, including confusion, blindness, bleeding tendency, heart failure and hypertension. With macroglobulinemia, paraproteinemic polyneuropathy, cold hemolytic anemia, and cryoglobulins are often noted. In other types of lymphomas and chronic lymphocytic leukemia, paraproteins of the IgM class are observed in 20% of patients, but the paraprotein concentration is usually lower than 30 g / l.

Heavy chain disease (Franklin's disease) is accompanied by the synthesis of only the IgG-gamma heavy chain, without an accompanying light chain. This extremely rare disease is manifested by edema of the soft palate and lymphoid infiltration. Also rare is alpha heavy chain disease, which causes chronic diarrhea, malabsorption due to lymphoid infiltration of the intestinal wall.

In screening examinations, the incidence of paraproteinemia increases sharply in the population after reaching 50 years of age and reaches 4–10% in people over 65 years of age. However, the majority of newly diagnosed paraproteinemias in the general population are asymptomatic monoclonal gammopathy of unknown significance (MGUS). The concentration of paraprotein in MGNS is significantly below 30 g/l and usually does not exceed 10–15 g/l. In addition, with MGNS, the paraprotein is detected against the background of polyclonal immunoglobulins, i.e., there is no inhibition of the normal synthesis of other immunoglobulins. The term "MGNZ" refers to cases of paraproteinemia without other signs of oncohematological disease, which require annual monitoring in order not to miss the moment of malignancy of the process. If paraproteins are detected in those examined younger than 50 years, even more frequent re-examinations are necessary, since they have a high risk of developing multiple myeloma. If the M-protein concentration is more than 15 g/l, regardless of age, it is recommended to conduct an extended examination, including electrophoresis of a 24-hour urine sample and immunofixation every 3–6 months, since the risk of malignant transformation is very high. Allocate benign paraproteinemia, which is characterized by the preservation of the paraprotein without progression to multiple myeloma or other disease within 5 years of follow-up. In transient paraproteinemia, the paraprotein concentration is usually below 3 g/L.

Indications for the appointment of the study:

1. Paraprotein typing.

2. Differential diagnosis of monoclonal gammopathy.

3. Evaluation of the effectiveness of ongoing therapy for myeloma and other gammopathy.

Interpretation of results:

Positively:

• Monoclonal gammopathy of unknown significance, benign paraproteinemia;
• multiple myeloma;
• Macroglobulinemia Waldenström;
• Lymphoma and chronic lymphocytic leukemia;
• heavy chain disease;
• Paraproteinemic polyneuropathy;
• AL amyloidosis or light chain deposition disease;

Negative:

• Normally, the M-gradient is not found in the serum.

Dalrymple (Dalrymple, 1846), Bence-Jones (N. Vepse-Jones, 1848), Macintyre (W. Macintyre, 1850) first reported a disease characterized by pain in the bones, softening and increased fragility of the bones, as well as the presence in the urine of a special thermolabile protein substance. O. A. Rustitsky in 1873 described in detail the pathoanatomical picture, and Kahler (O. Kahler) in 1889 presented a clinical, morphological and pathogenetic analysis of the disease, in connection with which it was called Rustitsky's disease - Kahler. In 1949, G. A. Alekseev introduced the term "multiple myeloma", which combines the diversity pathological changes in the bone marrow, bones, kidneys and other organs, as well as protein pathology syndrome.

Multiple myeloma usually occurs over the age of 40 and affects men and women equally often. The prevalence of the disease in Western European countries, the USSR and the USA is 1.1-3.1, and the mortality rate is 0.8-1.0 per 100,000 inhabitants.

Etiology. The hypothesis of somatic mutation in immunocompetent B-lymphocytes seems likely. No specific chromosomal aberrations were found in multiple myeloma.

Immunochemical classification Multiple myeloma is based on the difference in classes of immunoglobulins (paraproteins) synthesized and secreted by mutant plasma cells. Allocate G-, A-, D and E-myeloma. The number of patients with G-myeloma is about 60%; A-myeloma - about 25%; D-myeloma - about 3% of all patients with multiple myeloma; E-myeloma is one of the rarest forms. The paraprotein is also typed according to the light chains (k or A,) that make up its molecule. In addition, Bene-Jones myeloma (the so-called light chain disease) is isolated, in which the paraprotein is represented by light chain dimers of types or X. This form of myeloma

accounts for about 10% of all forms of myeloma Bence-Jones' myeloma should not be identified with Bence-Jones' proteinuria, which can be detected in any form , which is associated with a violation of the mechanism of synthesis and secretion of paraprotein by plasma cells.

The pathogenesis of multiple myeloma is associated with proliferation in the bone marrow and less often in other organs of plasma cells (see full body of knowledge), which have the property of infiltrating destructive growth with the secretion of a monoclonal high molecular weight (200,000-300,000) immunoglobulin (paraprotein) and with the suppression of normal clones of immunocompetent cells (See full body of knowledge).

The consequence of tumor growth of plasma cell infiltrates in the bone marrow is the destruction of the bones of the skeleton. Extramedullary myelomas may have the property of malignant tumors developing in various organs and tissues (stomach, intestines, lungs, lymph nodes, and so on), while the process of metastasis, apparently, also takes place.

Secretion into the bloodstream and into the surrounding tissues of the paraprotein causes the development of the so-called hyperviscosity syndrome (syndrome of increased blood viscosity) and tissue dys- (para-) proteinosis. Suppression of normal clones of immunocompetent cells leads to the development of immunodeficiency syndrome (see Immunological deficiency), in which there is a tendency to repeated (especially respiratory) infections. An important link in the pathogenesis of multiple myeloma is the development of amyloidosis (paraamyloidosis), which is observed in 10-20% of patients (more often with D-myeloma and light chain disease) and is one of the manifestations of tissue dysproteinosis (see full body of knowledge Amyloidosis). In this case, the main component of the protein of amyloid fibrils is the light chains of the paraprotein molecule or their fragments.

Paraproteinosis of the kidneys in combination with blockade of the tubules by protein agglomerates and often developing ascending urological infection - pyelonephritis (see the complete body of knowledge) - form the pathogenetic basis of myeloma nephropathy ("myeloma kidney") with insufficiency of kidney function and the development of uremia (see the full body of knowledge Renal failure) .

Pathological anatomy. Morphologically, the substrate of multiple myeloma is tumor growths of plasma cells that first appear in the bone marrow. The process is localized mainly in the bones and in most cases is accompanied by a sharp resorption of bone tissue (see Osteoporosis). At the same time, as a rule, there are signs of a violation of protein metabolism in the form of tissue dis(para-) proteinosis. The combination of these changes determines the pathoanatomical picture of the disease characteristic of multiple myeloma.

At autopsy, the most typical changes are found in flat and sometimes tubular bones. They are fragile, soft, often cut with a knife. There may be fractures, bone deformities, in particular compression of the vertebral bodies, sometimes with compression spinal cord. In the diffuse-nodular form of multiple myeloma, which is most common in the advanced picture of the disease, the bone marrow on the cut has a variegated appearance, contains multiple grayish-pink nodular growths of various sizes (color figure 8). In the nodes and around them, due to hemorrhages and necrosis, dark red and yellowish areas are often detected. Tumor masses sometimes grow into adjacent tissues (muscles, skin, pleura, dura mater, and so on). At diffuse form Myeloma bone marrow is juicy, variegated due to the alternation of proliferation of plasma cells, hemorrhages, necrosis. The number of bone plates is reduced, the cortical layer is thinned. In rare cases, osteoporosis is absent. The size and weight of the spleen, liver, lymph nodes are usually within the normal range or slightly enlarged. In some cases, there is a significant increase in their volume due to a massive specific lesion. Rare cases of the development of extensive nodular growths in the skin, pleura, lungs, kidneys, brain and other are described. The kidneys can be enlarged, pale, smooth; with pronounced sclerotic changes, a picture of a secondary wrinkled kidney is revealed. In some cases, there are point and spotted hemorrhages in the skin, serous and mucous membranes, tissue of internal organs. As a rule, signs of general anemia, dystrophy of parenchymal organs, often purulent-inflammatory processes are found.

Histologically, in the bone marrow with multiple myeloma, proliferation of plasma cells is found. various kinds. Histologically, plasma cells in multiple myeloma are most often characterized by a rough, eccentrically located nucleus and a fairly abundant basophilic cytoplasm; sometimes the core fine structure chromatin contains 1-3 nucleoli, and the basophilia of the cytoplasm is weakly expressed. There are various transitional forms between these variants (Figure 1); for multiple myeloma is characterized by the presence of giant two and multinuclear plasma cells and so the groove. flaming cells, the abundant cytoplasm of which has uneven contours and a pinkish tint along the edges. Often there are various variants of plasma cells containing Russell's acidophilic bodies, the number and location of which in the cytoplasm determine the type of cells referred to as grape cells, morula cells, thesaurocytes (accumulation cells) or Mott cells. Some authors have observed cytochemically negative crystalline inclusions in the cytoplasm of myeloma cells.

Rice. one. A micropreparation of bone marrow punctate from a patient with multiple myeloma ( different types plasma cells): a - a typical plasma cell with coarse nuclear chromatin and sharply basophilic cytoplasm; b - a plasma cell with a fine structure of nuclear chromatin and weakly basophilic cytoplasm; c - binuclear plasma cell; gram - "flaming" plasma cell; e - plasma cell with Russell bodies; fields of micropreparations are covered with erythrocytes.

Electron microscopy of plasma cells in multiple myeloma reveals hypertrophy of protein-synthesizing structures - a rough endoplasmic reticulum in the form of sacs and cisterns pushing the nucleus to the periphery, polyribosomes and a developed Golgi complex. Acidophilic bodies are detected in the form of optically dense granules containing an amorphous protein substance. They are believed to be composed of a condensed paraprotein. Due to the high content of protein and ribonucleoproteins, the cytoplasm of these cells is sharply pyroninophilic, has a PAS-positive reaction, and luminesces when stained with thioflavin T. Along with mature plasma cells, plasmablasts, atypical giant single and multinucleated cells are detected. Cellular composition overgrowth varies in various occasions and often differs in different parts of the skeleton. Plasma cell outgrowths may be nodular, diffuse, or diffuse nodular. The first variant, as the results of trepanobiopsy show, occurs mainly in the early stages of the disease. At the same time, against the background of normal bone marrow, multiple, rather large (from 200 micrometers and more) focal growths of plasma cells (Figure 2), penetrating into the adjacent tissue, are detected. Progression Myeloma is characterized by the development of diffuse infiltration of the bone marrow by plasma cells (Figure 3). Often this is accompanied by the development of extensive nodular growths (color table, art. 33, figures 8 and 9). The number of cells of normal hematopoiesis is markedly reduced. Fields of myelofibrosis, fat cells can be detected. Characterized by a significant thinning of the bone plates up to their complete disappearance in large areas, the expansion of osteon channels (Haversian channels), partial destruction of the cortical substance with the germination of plasma cells into the periosteum. Bone resorption proceeds by the type of smooth, axillary and osteoclastic resorption. It is believed that osteoporosis is caused by a violation of the processes of bone formation due to increased secretion in the bone marrow of a factor that stimulates osteoclasts. Reparative processes are sharply reduced, however, in a number of cases, focal bone formation of a primitive structure is observed, mainly in the area of ​​microfractures and in areas of hemorrhages along the periphery of nodular growths (Figure 4). Occasionally, there is no resorption of bone tissue, there is a thickening of the bone plates.

Microscopically, nodular and diffuse proliferates of plasma cells are often detected in the spleen, liver, lymph nodes, and other organs. Often found calcareous metastases in the kidneys, lungs and other organs. Differences in the frequency and intensity of specific lesions of internal organs in various immunochemical variants of multiple myeloma were not found.

Tissue paraproteinosis is expressed in the accumulation of protein masses in the lumen of blood vessels, protein impregnation of their walls and stroma of organs, the deposition of amyloid (paraamyloid) and occasionally crystalline substances. Protein, amyloid-like deposits are oxyphilic, stain positively in the PAS reaction, unlike amyloid, they do not have anisotropy. In the kidneys, especially with prolonged Bens-Jones proteinuria (see the complete code of knowledge of Bens-Jones protein), a picture of paraproteinemic nephrosis develops. Characterized by an abundance of protein cylinders in the tubules (Figure 5), degeneration of the epithelium, its death and desquamation, focal nephrohidrosis, edema, plasma cell infiltration of the stroma is possible. Cylinders may be surrounded by giant cells, impregnated with calcium salts. Glomerular changes are insignificant. There is a thickening of the basement membrane, deposition of protein substances in the mesangium, sometimes hyperplasia of its cells; dystrophy of podocytes with the deposition of protein granules in their cytoplasm. Nephrosclerosis is often observed (see full body of knowledge). Myeloma is characterized by protein edema of lung tissue (Figure 6), myocardial stroma. Amyloid (paraamyloid) in multiple myeloma differs from its other varieties in the high content of low molecular weight fragments in the protein component. Amyloid often does not positive reaction with red Congo, metachromasia with methyl violet and toluidine blue; luminesces with thioflavin T and S, has anisotropic properties.

Rice. 2. Bone marrow micropreparation for multiple myeloma (trephine biopsy): 1 - plasma cells forming focal growths; 2 - areas of normal hematopoiesis; staining with hematoxylineosin; ×400. Rice. 3. Micropreparation of the bone marrow in multiple myeloma (trephine biopsy): 1 - diffuse infiltration of the bone marrow by plasma cells; 2 - bone tissue; staining with hematoxylin-eosin; × 80. Rice. 4. Micropreparation of a vertebra in multiple myeloma: 1 - infiltration of the periosteum with plasma cells; 2 - area of ​​micro-fracture; 3 - bone marrow fibrosis; 4 - formation of bone substance; staining with hematoxylin-eosin; × 140.

Characterized by a predominant lesion of the walls of blood vessels, heart, tongue, striated muscles, nerves, skin, tendons and synovial membranes of the joints. Perhaps a massive deposition of amyloid in myeloma nodes in the bones with the formation of large tumors of a peculiar kind. In rare cases, crystalline substances precipitate in plasma cells and extracellularly in tumor growths, as well as in the kidneys and corneal vessels, the origin of which is associated with a violation of the synthesis of light x-chains. When treated with cytostatics in the bone marrow, a decrease in the volume of tumor growths is observed in combination with the development of hypoplastic changes, sclerosis fields, and the formation of imperfect bone substance.

clinical picture. In a typical course, the main clinical symptom is bone pain (ossalgia), which is most often localized in the spine, ribs, less often in tubular bones and in the bones of the skull. The growth of a tumor or diffuse plasma cell infiltrates outside the bone tissue is accompanied by radicular pain (see the full body of knowledge Radiculitis), paraplegia (see the full body of knowledge), hemiplegia (see the full body of knowledge), exophthalmos (see the full body of knowledge), and so on. infiltration of the pleura or peritoneum with the development of specific pleurisy (see the full body of knowledge) or ascites (see the full body of knowledge) and with a high content of plasma cells and paraprotein in the exudate. With organ localization of plasma cell tumors (lungs, stomach, intestines, lymph nodes, liver, spleen, and others), the clinical picture corresponds to that in malignant tumor of this organ or supplemented by symptoms such as enlarged lymph nodes, liver, spleen, etc.

Some researchers distinguish plasma cell leukemia as an independent nosological form, which, unlike ordinary multiple myeloma, in addition to an increased content of plasma cells in the blood, is characterized by a pronounced hemorrhagic diathesis associated with thrombocytopenia, rapid course and extensive plasma cell infiltration in various organs.

In the study of blood at the beginning of the disease, an accelerated ESR is detected, which is associated with the predominance of coarse proteins (paraproteins) in the plasma, which are detected by electrophoresis (Figure 7). The belonging of a paraprotein to one of the Ig classes is determined using immunoelectrophoresis (see the full body of knowledge) with monospecific antisera (Figure 8) or radial immunodiffusion on agar gel according to Mancini (see the full body of knowledge Immunodiffusion.); the latter method is also used for the quantitative determination of paraproteins. Using the same methods and using simple diffusion on agar, using monospecific antisera against K and X light chains, the type of Ig light chains is determined. Myeloma is characterized by a decrease (depression) in the concentration of non-paraprotein immunoglobulins (the so-called "non-M-components" or physiological immunoglobulins), which is associated with impaired humoral immunity.

As the disease progresses, normochromic normocytic non-hemolytic anemia develops, less often - thrombocytopenia; plasma cells often appear in the blood, the number of which can reach 10-50% or more of all blood cells. In the latter case, one usually speaks of leukemia Multiple myeloma

In some patients with multiple myeloma, a blood test reveals such signs of dyshemopoiesis as erythroblastemia, macrocytosis and even megalocytosis of erythrocytes, and a leukemoid (myeloid) shift in the leukocyte count; sometimes there is lymphocytosis as a reflection of the immunoproliferative process in the bone marrow.

Of the complications, one should keep in mind pathological bone fractures in the places of their tumor destruction (see Fractures), the development of paraparesis and plegia in the compression of the brain or spinal cord by a tumor growing from the bones of the skull or vertebrae. Secondary radicular syndrome occurs due to plasma cell infiltration of the meninges and compression of the roots of the spinal nerves.

The development of paraamyloidosis of the kidneys in combination with the blockade of the tubules by protein agglomerates usually leads to functional failure of the kidneys with the development of irreversible uremic intoxication. The deposition of amyloid in the myocardium reduces its contractility; there are cases when the deposition of amyloid in the myocardium in multiple myeloma was erroneously diagnosed as a heart attack or an aneurysm of the heart. There are also complications (polyneuropathies, arthropathy, and so on) associated with different localization of paraamyloidosis in multiple myeloma

Sometimes with multiple myeloma, as with Waldenström's disease (see Waldenstrom's disease), a hyperviscosity syndrome develops, which consists of hemorrhages and symptoms of cerebropathy, retinopathy and is associated with the circulation of complexes of globulin molecules in the bloodstream. At the same time, various disorders in the blood coagulation system are revealed. Approximately 30% of patients with multiple myeloma in severe cases have an increase in the calcium content in the blood of more than 6 mi-equivalent, which is most often associated with intense bone resorption and impaired excretion of calcium in the urine. Clinical, the picture of hypercalcemia in multiple myeloma is expressed by hyperreflexia, muscle rigidity, drowsiness, lethargy; some patients develop disorientation and even psychosis, as well as stuporous and coma, which may disappear when the level of calcium in the blood is normalized.

A great danger in multiple myeloma is infectious complications associated with an immunodeficiency state. Most often develop respiratory infections(bronchitis, pneumonia) with a protracted, recurrent course. Ascending urological infections cause pyelonephritis; various pustular lesions of the skin and mucous membranes can lead to the development purulent meningitis, phlegmon, sepsis, and the like Among the causes of death in patients with myeloma, pneumonia, urosepsis, uremia, and pulmonary heart failure predominate. In some cases, death is due to cerebral hemorrhage, paraproteinemic coma.

The diagnosis of multiple myeloma should be established as soon as possible. early dates to apply timely treatment and prevent such unreasonable appointments as active physiotherapy and balneological procedures.

The diagnosis is established on the basis of clinical picture (pain in the bones, especially in the spine), blood tests (accelerated ESR, hyperproteinemia, hypergammaglobulinemia, the presence of an M-gradient) and urine (Bence-Jones proteinuria). The reliability of the diagnosis is confirmed by a study of bone marrow punctate, which, as a rule, reveals the proliferation of plasma cells, the number of which exceeds 10%, sometimes reaching 70-100%.

For the diagnosis of multiple myeloma, along with a cytological analysis of sternal punctate, since the beginning of the 60s, intravital histological examination"Crumbs" of the bone marrow obtained by bone puncture, or more often, a trephine biopsy is performed (see the full body of knowledge). A number of oncologists note the value of this method for the diagnosis of multiple myeloma in cases of a small number or absence of plasma cells in the punctate. Identification of the paraprotein class using immunoelectrophoresis and radial immunodiffusion expands the understanding of the nature of the process, and also helps in differential diagnosis.

X-ray diagnostics. X-ray changes in the skeletal system in multiple myeloma are very diverse. The following clinical and radiological forms of multiple myeloma are distinguished: 1) multiple-focal, or multiple-nodular, 2) diffuse-porotic, 3) osteosclerotic, and 4) solitary (isolated).

The multiple-focal form occurs in more than 70% of cases, radiologically characterized by the formation of multiple rounded defects with a diameter of up to several centimeters. Changes are detected most often in flat bones (Figure 9), less often in long and short tubular bones. Each defect is clearly contoured; there are no reactive changes from the surrounding tissue. In the tubular bones, the cortical substance becomes thinner from the inside, the medullary cavity expands, in place of the largest nodes, the bone swells slightly and thickens (Figure 10, a). In some cases, complete destruction of the cortex of the bone can be observed (Figure 10, b) with the spread of the tumor in soft tissues. A characteristic picture is revealed when the bones of the skull are affected, in which multiple, as if knocked out by a punch, bone defects are visible (Figure 11). In the spine, diffuse rarefaction of the bone structure, flattening of the vertebral bodies (brevispondylia, "fish vertebrae"), and curvature of the spinal column are found. Against the background of diffuse rarefaction of the bone substance of the vertebral bodies, the emphasis of the arches and processes of the vertebrae is noticeable, which, as a rule, is absent in metastatic lesions of the spine.

Diffuse-porotic form occurs in 9-15% of cases and is characterized by general widespread osteoporosis of the skeletal system (see Osteoporosis) without limited foci of bone resorption. Often it is not a separate form, but a phase of the disease, which then turns into a multiple-focal form of the lesion, which dictates the need for repeated x-ray studies of the skeleton. With this form, the x-ray picture can remain normal for a long time. The gradually emerging general demineralization of the skeleton is devoid of specificity and does not differ from systemic osteoporosis of another origin. However, this osteoporosis can have character traits, be fine-grained, in some cases coarse-grained or spotty in nature and most often localized in the flat bones of the skull, pelvis, ribs.

The osteosclerotic form is rare (in about 3% of cases) and is manifested by severe osteosclerosis of focal-nesting or diffuse nature (see Osteosclerosis) and sometimes gives an x-ray picture of a marble vertebra (see full body of knowledge).

The solitary form (solitary myeloma) is observed even less frequently; Some researchers, such as A. S. Reinberg, consider this form as an early phase of multiple myeloma, others as an independent disease (primary tumor of the bone marrow, which has all the signs of tumor growth). Solitary myelomas most often occur in the pelvic bones (usually in the iliac wing), spine, bones of the cranial vault, ribs, less often in the proximal humerus or femur. Radiologically, two varieties of this form can be distinguished: a classic purely destructive large solitary bone defect, clearly delimited from the surrounding tissue (Figure 12), and cystic trabecular myeloma - a large cystic or cellular formation (Figure 13). There is usually no reactive sclerosis around the tumor node. In rare cases, solitary myeloma can occur in other organs and tissues. Solitary myeloma of the stomach radiographically gives a picture similar to infiltrative cancer or gastric lymphogranulomatosis.

Differential diagnosis should be carried out with various diseases of the bones, in particular the spine (spondylarthrosis, tuberculous spondylitis, Bechterew's disease, and others), as well as with metastases of malignant neoplasms in the bone (cancer of various localization, sarcoma). The main diagnostic value in this case is the morphological study of punctates (trepanates) of the bone marrow, proteinogram and immunochemical data.

Myeloma Bene-Jones, in which sometimes long time the only symptom is persistent proteinuria, distinguished from chronic diseases kidneys based on a heat test for Bence-Jones protein in the urine or urine electrophoresis.

The main criteria for the differential diagnosis of multiple myeloma and Waldenström's macroglobulinemia are the identification of a paraprotein and the presence of plasma cell proliferation in the bone marrow. In Waldenström's disease, the paraprotein is class IgM and the bone marrow is infiltrated with lymphatic cells. X-ray examination of the bones of the skeleton, as a rule, in Waldenström's disease does not reveal foci of osteolysis characteristic of multiple myeloma; an external examination of a patient with Waldenström's disease often reveals signs of systemic lymphoid hyperplasia (enlarged lymph nodes, liver, spleen), rare in multiple myeloma

Differential diagnosis between multiple myeloma and symptomatic paraproteinemias with reactive plasmacytosis in collagenoses, chronic diseases liver, tuberculosis, malignant neoplasms, leukemias, lymphomas, and so on, is based on the difference in clinical, picture, morphological data (unlike myeloma, in symptomatic paraproteinemias, plasma cells lie in the form of small clusters or single elements scattered in the tissue) and radiological signs. Importance is attached to the dynamics of the M-gradient, the value of which in symptomatic paraproteinemias correlates with the degree of activity of the underlying disease. Concentrations of physiological Ig in their study by the method of radial immunodiffusion are usually normal or slightly increased in symptomatic paraproteinemias and clearly reduced in multiple myeloma

Variety of radiological manifestations Myeloma requires differential diagnosis with other diseases. The greatest difficulties arise in the differential diagnosis of multiple focal forms of myeloma with cancer metastases in the bone. Differentiation is based on a complex of clinical, laboratory and radiological data. Myeloma nodes are most often located in the ribs and sternum; unlike cancer metastases, they do not cause a periosteal reaction and osteosclerosis.

Of certain importance is the differential diagnosis with osteomalacia (see the full body of knowledge), hyperparathyroidism (see the full body of knowledge) and Recklinghausen's generalized fibrous osteodystrophy (see the full body of knowledge Parathyroid osteodystrophy). In osteomalacia, osteoporosis is more diffuse, and there are no rounded bone defects characteristic of myelomas. Hyperparathyroidism and Recklinghausen's disease are distinguished by the larger size of individual defects, the predominant lesion tubular bones.

Of the diseases of the blood system, multiple myeloma should be differentiated from those forms of leukemia (see full body of knowledge) that can occur with pronounced destructive changes in the skeleton. In such cases, first of all, data from bone marrow and serum proteins are taken into account.

Certain difficulties may arise in the differential diagnosis of multiple bone eosinophilic granuloma (see full body of knowledge). The discrepancy between the extensive destructive process and the general good condition of the patient, the absence of changes in the hemogram and paraproteinemia suggest multiple eosinophilic granuloma. The final diagnosis is based on puncture or biopsy data from the lesion.

Of practical importance is the differential diagnosis of osteoporotic changes in multiple myeloma with widespread osteoporosis of various etiologies, in particular dishormonal ones. In multiple myeloma, osteoporosis is widespread throughout the skeleton, in contrast to dyshormonal osteoporosis, which is limited mainly to the spine and ribs.

Myeloma must be differentiated from the so-called essential benign gammopathy, in which accelerated ESR, moderate hyperproteinemia and M-gradient in the zone of γ or β-globulins are detected, but there are no morphological and radiological signs Myeloma and there is no basis for the diagnosis of any disease that can cause symptomatic paraproteinemias. The criterion for essential benign gammopathy is the stability of the concentration of paraprotein and physiological Ig.

Treatment. The first course of therapy is usually carried out in a hospital; further treatment can be carried out on an outpatient basis under the supervision of a doctor and with regular (at least 1 time per week) blood test.

The agents used are aimed at suppressing the proliferation of a pathological clone of plasma cells producing paraprotein. Mainly alkylating cytostatic drugs are used: sarcolysin and cyclophosphamide. Along with these drugs, cytostatic phase-specific chemotherapy drugs, such as natulan, vincristine, are used. The use of corticosteroid hormones (at a daily dose of 30-40 milligrams of prednisolone) increases the effectiveness of any chemotherapy for multiple myeloma In treatment regimens that involve the appointment of loading doses of chemotherapy, doses of prednisolone are increased to 100-150 milligrams per day or more. The doses of chemotherapy drugs used and the intervals between their administration are strictly individual. The choice of dose depends on the initial state of the patient, on the sensitivity to the drug. So, sarcolysin is preferable for intact hematopoiesis (the number of leukocytes is not less than 4000 in 1 microliter and platelets - 100,000 in 1 microliter) and with normal kidney function. The appointment of cyclophosphamide is acceptable for leukopenia, thrombocytopenia, and also for moderate azotemia. With a pronounced immunodeficiency state of the body, large doses of cytostatic drugs should be avoided. Replacement of the drug, as well as the use of combined treatment regimens with these drugs, are recommended when resistance to one of them develops.

Sarcolysin is usually given at a dose of 5 to 10 milligrams orally or intravenously daily or every other day (some recommend sarcolysin 10 to 20 milligrams per week); 200-300 milligrams per course of treatment (with intravenous administration course dose rarely exceeds 150-200 milligrams). Treatment is repeated up to 5-6 courses or more with a break of 1g / 2-2 months

Cyclophosphamide is used intravenously in a single dose of 200-600 milligrams with an interval of 1-2 days; the dose per course is 8-10 g, the intervals between courses are 1-1½ months Large doses of cyclophosphamide up to 1000 milligrams can be administered once a week. With a pronounced radicular syndrome due to specific infiltration of the membranes of the spinal cord, cyclophosphamide is injected into the spinal canal. In polychemotherapy, the listed drugs are used in various combinations.

Common Tactic radiotherapy Myeloma In generalized forms, remote gamma therapy is prescribed as an adjunct to large foci of destruction in the supporting bones with a pronounced pain (especially radicular) syndrome and with rapid growth tumors with the threat of a pathological fracture of the bone or compression of the spinal cord or brain. In this case, radiation therapy with a total dose of 4500-5000 rad per focus is prescribed simultaneously with chemotherapy or precedes it. Radiation therapy acquires independent significance with solitary me scrap; in these cases, it is prescribed after the removal of the tumor.

In cases of clinically pronounced hyperviscosity syndrome, 7-10 plasmapheresis sessions are indicated (see full body of knowledge) with the extraction of 500-700 milliliters of plasma per session; if necessary (anemia), transfusions of donor blood are simultaneously performed. In multiple myeloma with leukopenia and thrombocytopenia, it is advisable to use component transfusion therapy; with developing renal failure - all the means used in renal failure of any origin, up to hemodialysis (see full body of knowledge), the use of which is limited, since the development of uremic intoxication in multiple myeloma usually coincides with the terminal stage of the disease.

Infectious complications require the use of maximum tolerated doses of antibiotics, preferably broad-spectrum antibiotics in various combinations of 2-3 drugs.

With hypercalcemia, active cytostatic therapy is carried out in combination with increased doses of corticosteroid hormones (prednisolone up to 100 mg per day intravenously), hydration and plasmapheresis. Of the symptomatic agents, analgesics, vitamins (D), anabolic hormones are often used.

Surgical treatment is indicated for solitary myeloma and can be used as additional remedy to chemotherapy and radiation therapy in generalized forms, if the location of one of the tumor foci threatens the important functions of closely located or directly involved organs or parts of the body (laminectomy and removal of the tumor in order to decompress the spinal cord, orthopedic and reconstructive operations in the destruction of large tubular bones, etc.). With pronounced destructive changes in the spine, corrective measures include light traction on an inclined plane, a lightweight corset, and it is also recommended to sleep on a shield.

Forecast. At proper treatment restoration of the patient's activity and objective signs of a decrease in the mass of tumor cells (decrease in the concentration of paraprotein, tumor size) are observed in 70% of patients. Life expectancy depends on the nature of the complications, as well as on individual features course of the disease, probably associated with the proliferative activity of plasma cells, and with a favorable response to treatment is 2-4 years, in some cases exceeds 10 years.

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Monoclonal Gammopathy(immunoglobulinopathy, paraproteinemia) are a heterogeneous group of diseases characterized by monoclonal proliferation of B-lymphoid cells that secrete immunoglobulins.

Basic distinctive feature these diseases is the production of monoclonal immunoglobulin (M-component, M-gradient, M-protein, paraprotein), which is determined in blood serum and / or urine.

The bulk (almost 80%) of all immunoglobulins make up IgG, which provide all the variety of antibodies to bacteria, their toxins, viruses and other antigens. Normal IgG is a mixture of 4 subclasses: IgG1, IgG2, IgG3 and IgG4. All types of IgG cross the placenta and provide passive immunization of the fetus. The ratio of IgG of different subclasses in the paraprotein in multiple myeloma and monoclonal gammopathy of unknown origin does not differ from the ratio in normal serum.

Class A immunoglobulins(about 20% of all immunoglobulins) are found in blood serum, there are many of them in secrets (intestinal and respiratory tracts, saliva, lacrimal fluid, milk). They have antiviral and antimicrobial activity, prevent the penetration of microorganisms through the mucous membranes. Class M immunoglobulins are determined mainly on the surface of B-lymphocytes and play a major role in the first stage of the immune response in bacteremia and viremia on early stages infections. Class D immunoglobulins are found in serum in very small amounts (less than 1%), their function is still unclear.

Small amounts in serum blood contains IgE, their content increases with allergic diseases and helminthic infestations.

On electrophoresis, normal immunoglobulins, heterogeneous in their properties, are located in the y zone, forming a gently rising plateau on the electrophoregram or a wide band during immunofixation. Monoclonal immunoglobulins, homogeneous in all physicochemical and biological parameters, migrate mainly to zone y, rarely to zone b and even a, where they form a high peak or a clearly demarcated band. Until now, many countries use the method of electrophoresis on cellulose acetate, which allows you to detect the presence of a paraprotein if its content in serum exceeds 7 g / l.

Monoclinal Gammopathy

First 1970s. The most common method has become agarose electrophoresis, which makes it possible to determine monoclonal immunoglobulin at a concentration of at least 0.5 g/l in blood plasma, and 0.002 g/l in urine. To determine the class and type of immunoglobulin, the method of immunofixation is used using monospecific antisera to heavy and light chains of immunoglobulins. The amount of paraprotein is determined by electrophoregram densitometry.

tumor cells paraproteinemic hemoblastoses retain the differentiation of normal lymphoid and plasma cells and the ability to a high level of synthesis and secretion of immunoglobulin. In both normal and pathological immune responses, each plasma cell can synthesize and secrete up to 100,000 antigen-specific immunoglobulin molecules every minute. Based on the synthesis and secretion of electrophoretically and immunochemically homogeneous immunoglobulin and the correspondence of its amount to the mass of the tumor, it was shown that malignant plasma cells are monoclonal, i.e., they originate from one transformed lymphocyte or plasma cell.

Fine intracellular synthesis of H- and L-chains in cells producing antibodies is well balanced. In a number of cases, in malignant clones, the balance between the synthesis of H- and L-chains is disturbed in the direction of increased production of the latter. Monoclonal dimers and monomers of L-chains, having a small molecular weight, are filtered by the renal glomeruli, then partially reabsorbed and catabolized in the renal tubules, and partially excreted into the urine (Bence-Jones protein).

The structure of H-chains, apparently, remains normal in multiple myeloma and Waldenström's macroglobulinemia.

Malignant plasma cell proliferations, such as multiple myeloma, Waldenström's macroglobulinemia, are characterized by the production of monoclonal immunoglobulin and certain clinical symptoms. M-protein in a number of cases is found in practically healthy people. In such cases, we speak of monoclonal gammapathies of undetermined significance (MGUS, MGUS - monoclonal gammapaties of undetermined significance).

In the 60-70s of the XX century, when electrophoresis technique on cellulose acetate, monoclonal gammopathy was diagnosed in 0.7-1.2% of the healthy population. Since the beginning of the 80s, after the introduction of a more sensitive technique - agar electrophoresis, M-paraprotein began to be detected in 5% of the healthy population aged 22 to 55 years (when electrophoresis on cellulose acetate was used in the same group, monoclonal gammopathy was registered only in 0.33%). The frequency of monoclonal gammopathy increases to 7-8% in the group over 55 years old and reaches 10% in the group over 80 years old, while in 80% of individuals with an identified M-gradient, its serum concentration is very low - less than 5 g / l.

According to the Mayo Clinic, of all monoclonal gammopathy in half of the cases, monoclonal gammopathy of unknown origin (MGNG) (52%) is detected, in 12% of patients - amyloidosis and in 33% - malignant paraproteinemias: multiple myeloma (19%), indolent myeloma (5%), solitary plasmacytoma (3%) , Waldenström's macroglobulinemia (3%), other types of lymphomas with paraprotein secretion (3%). In 3% of cases, monoclonal gammopathy accompanies other malignant tumors.

A key indicator for the diagnosis of a malignant protein-producing tumor is a high concentration of M-paraprotein in the blood serum.

Research has shown J. Moller-Petersen and E. Schmidt, the assumption of multiple myeloma turned out to be correct in 90% of cases with a serum M-paraprotein concentration of more than 30 g / l, and the assumption of MGNG - in 90% of cases with more low rates concentration of M-paraprotein.

Basic differential diagnostic criteria for distinguishing myoclonal gammopathy of unknown origin from smoldering myeloma and multiple myeloma

So the higher serum M-protein level, the more likely that the patient has developed a malignant tumor with paraprotein secretion.

Probability development of a malignant tumor associated with the duration of the existence of monoclonal. R. Kyle et al. (Mayo Clinic) observed a large group of patients with monoclonal gammopathy. With a follow-up duration of 10 years, malignant transformation occurred in 16% of MGUS patients, 20 years - in 33%, and with a follow-up of 25 years - in 40% of patients. The risk of transformation is 1-2% per year. Monocloanal gammopathy of unknown origin most often transforms into myeloma (68%), much less often in patients with monoclonal gammopathy of unknown origin (MGUS) there is a transformation into Waldenström's macroglobulinemia (11%) and lymphoma (8%), even less often - into heavy chain disease.

In most cases monoclonal gammopathy of unknown origin they will not have time to undergo malignant transformation, since in 80% of patients with monoclonal gammopathy, the concentration of M-paraprotein in the blood serum is significantly lower than 30 g/l, and the age of the absolute majority of persons with identified paraproteinemia exceeds 40 years.

Immoglobulin class, detected at monoclonal gammopathy of unknown origin(MGNG), largely determines the type of possible transformation. The risk of transformation into lymphoma or Waldenström's macroglobulinemia is higher in patients with unexplained monoclonal gammopathy (MGUS) and IgM production, while patients with unexplained monoclonal gammopathy (MGUS) with IgA or IgG production are more likely to transform into multiple myeloma, AL-amyloidosis, or other diseases accompanied by plasma cell proliferation.

The main medical tactic is to observe the patient - "watch and wait." Most often, monoclonal gammopathy of unknown origin transforms into myeloma, so it became necessary to systematize the criteria that determine the risk of such transformation and the monitoring algorithm. The table presents criteria for differentiating monoclonal gammopathy of unknown origin from smoldering myeloma, which also uses the “watch and wait” tactics, and from multiple myeloma, requiring chemotherapy.

Beyond the task primary differential diagnosis, there is the task of determining the tactics of patient management and predicting the possible transformation of monoclonal gammopathy of unknown origin.

AT last years a number of authors have proposed various prognostic criteria to help determine the follow-up algorithm and the need to start treatment.
Researchers from MD Anderson Cancer Center(USA) in a multivariate statistical analysis showed that the most significant prognostic factors are the level of paraprotein in the blood serum and the presence of spinal lesions according to magnetic resonance imaging (MRI). A low risk of transformation was in patients with no changes in the spine according to MRI and a paraprotein level of 30 g/l or less; the median follow-up to progression was 79 months. The intermediate risk group included patients who had either MRI changes or paraprotein levels above 30 g/l. The median time to progression was 30 months. A high risk of transformation was in the group of patients who had both MRI changes and paraprotein level > 30 g/l; median to progression 17 months.

For patients in the intermediate prognostic group, an additional prognostic factor was the type paraprotein- IgA. When normal MRI was combined with the absence of other risk factors or the presence of only one of them, the median to progression was 57 months, and the presence of MRI changes in combination with one or two prognostic factors reduced the median to progression to 20 months. Not all investigators confirm the poor prognostic value of IgA paraprotein type.

In recent years, there have been research aimed at identifying cytogenetic changes that could predict close transformation of monoclonal gammopathy of unknown origin. The method of fluorescent in situ hybridization (FISH) revealed rearrangement of 14q32 in almost half of patients with monoclonal gammopathy of unknown origin, a deletion of chromosome 13 was detected 2 times less often than in multiple myeloma, and t(4;14) was almost never found in monoclonal gammopathy of unknown origin ( 2%). Correlations of these cytogenetic changes with clinical course with monoclonal gammopathy of unknown origin, it was not possible to identify.

Upon detection monoclonal gammopathy of unknown origin and after confirming this diagnosis in accordance with modern requirements, it is recommended to adhere to the following observation algorithm. In the absence of complaints in the patient during the first year, a study of the level of paraprotein is carried out every 3 months and MRI - after six months. If within 1 year the increase in the level of paraprotein and changes in MRI are not detected, in the future, the study of the paraprotein is performed 1 time in 6-12 months, and MRI - 1 time per year.