M urine gradient in vitro. Monoclonal gammopathies of unknown origin (mgng) - causes, options, diagnosis

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

The main distinguishing feature of 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 provides the full 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 to the fetus. The ratio of IgG of different subclasses in the paraprotein in multiple myeloma and monoclonal gammopathies of unknown origin does not differ from the ratio in normal serum.

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

In small quantities in serum blood contain IgE, their content increases in allergic diseases and helminthic infestations.

Electrophoresis shows normal immunoglobulins, heterogeneous in their properties, are located in zone y, forming a gently rising plateau on the electropherogram or a wide band during immunofixation. Monoclonal immunoglobulins, homogeneous in all physicochemical and biological parameters, migrate predominantly 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 cellulose acetate electrophoresis method, which makes it possible to detect the presence of paraprotein if its content in the serum exceeds 7 g/l.

Monoclinal gammopathies

Category of monoclonal gammopathies	Nature of the pathology	Concentration of monoclonal immunoglobulins in blood serum
1. B-cell malignancies	A. Multiple myeloma, Waldenström's macroglobulinemia b. Plasmacytoma (solitary: bone and extramedullary), lymphoma, chronic lymphocytic leukemia, heavy chain disease	More than 25 g/l Significantly less than 25 g/l
2. B-cell benign	A. Monoclonal gammopathies of unknown origin b. AL amyloidosis (primary amyloidosis)	Less than 25 g/l Less than 25 g/l
3. Immunodeficiency states with an imbalance of the T- and B-links of the immune system	A. Primary (Wiskott-Oldrich, DiGeor-ga, Nezelof, severe combined immunodeficiency syndromes) b. Secondary (age-related, caused by the use of immunosuppressants, concomitant with cancer of a non-lymphoid nature, such as colon cancer, breast cancer, prostate cancer, etc.) V. Restructuring of the immune system after bone marrow transplantation d. Antigenic stimulation in early ontogenesis (intrauterine infection)	Less than 2.5 g/l Less than 2.5 g/l Less than 2.5 g/l Less than 2.5 g/l
4. Homogeneous immune response	A. Bacterial infections b. Autoimmune diseases such as cryoglobulinemia, systemic lupus erythematosus, rheumatoid arthritis, etc.	Less than 2.5 g/l Less than 2.5 g/l

At first 70s of XX century. The most common method has become agarose electrophoresis, which makes it possible to determine monoclonal immunoglobulin in a concentration of at least 0.5 g/l in blood plasma, and in urine - 0.002 g/l. To determine the class and type of immunoglobulin, the immunofixation method is used using monospecific antisera to the heavy and light chains of immunoglobulins. The amount of paraprotein is determined by electropherogram densitometry.

Tumor cells paraproteinemic hemoblastoses retain the differentiation of normal lymphoid and plasma cells and the ability for 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 molecules of antigen-specific immunoglobulin 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.

Normal 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 towards 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 undergo reabsorption and catabolism in the renal tubules, and are partially excreted in the urine (Bence Jones protein).

The H-chain structure appears to remain normal in multiple myeloma and Waldenström's macroglobulinemia.

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

In the 60-70s of the XX century, when it was used 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 into practice 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 cellulose acetate electrophoresis 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 of age and reaches 10% in the group over 80 years of age, 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 gammopathies of unknown origin (MGUS) are detected (52%), in 12% of patients - amyloidosis and in 33% - malignant paraproteinemias: multiple myeloma (19%), flaccid 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.

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

As studies have shown J. Moller-Petersen And E. Schmidt, the assumption of multiple myeloma was correct in 90% of cases with a serum M-paraprotein concentration of more than 30 g/l, and the assumption of MGUS was correct in 90% of cases with lower M-paraprotein concentrations.

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

Parameter	Monoclonal gammopathy of unknown origin	Smoldering myeloma	Multiple myeloma
M-component: IgG IgA	< 30 г/л < 10 г/л	> 30 g/l, stable > 10 g/l, but< 20 г/л, стабильно	> 30 g/l > 20 g/l
L-chains in urine	< 1 г/сут	> 1 g/day	> 1 g/day
Plasma cells in bone marrow trephine	< 10%	> 10%, but< 20 %	> 10%
Foci of damage to skeletal bones on radiography	No	No lytic lesions	Lytic lesions or osteoporosis
Magnetic resonance imaging of the spine	No focal lesion	Single, small lesions may be detected	Multiple lytic lesions or osteoporosis
b2-microglobulin level	Normal	Normal	High or normal
Plasma cell proliferative index	< 1 %	< 1 %	Maybe > 1%
Renal failure, hypercalcemia, anemia, bone pain, extramedullary lesions	None	None	Available

Thus, the higher serum M-protein level, the greater the likelihood that the patient has developed a malignant tumor with paraprotein secretion.

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

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

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

The main medical tactic is to monitor the patient - “watch and wait.” Most often, monoclonal gammopathy of unknown origin transforms into myeloma, so there is a need to systematize the criteria that determine the risk of such transformation and the observation algorithm. The table presents criteria that allow us to differentiate monoclonal gammopathy of unknown origin from smoldering myeloma, which also uses “watch and wait” tactics, and from multiple myeloma, which requires chemotherapy.

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

In recent years, a number of authors have proposed various prognostic criteria to help determine the observation algorithm and the need to initiate 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). The risk of transformation was low 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 until progression was 79 months. The intermediate risk group included patients who had either changes on MRI or a paraprotein level 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 a 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 a normal MRI was combined with no or only one other risk factor, the median time to progression was 57 months, and the presence of abnormal MRI in combination with one or two prognostic factors reduced the median time to progression to 20 months. Not all researchers confirm the unfavorable prognostic value of IgA type paraprotein.

In recent years there have been research aimed at identifying cytogenetic changes that could predict the imminent transformation of monoclonal gammopathy of unknown origin. The fluorescence in situ hybridization (FISH) method revealed a 14q32 rearrangement in almost half of patients with monoclonal gammopathy of unknown origin, 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%). It was not possible to identify a correlation between these cytogenetic changes and the clinical course of monoclonal gammopathy of unknown origin.

When found 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. If the patient has no complaints, paraprotein levels are examined every 3 months during the first year and an MRI is performed after six months. If within 1 year there is no increase in the level of paraprotein and no changes are detected on MRI, then a paraprotein study is performed once every 6-12 months, and MRI - once a year.

The basic principle of the electrophoretic research method is that molecules in solution that have an electric charge are shifted toward the oppositely charged electrode under the influence of electric field forces. The rate of migration of a substance in a medium with the same electric field strength depends on the size of the particles and their electric charge. In the case of protein molecules, due to their amphoteric properties, the direction and speed of displacement largely depend on the pH of the environment in which migration occurs. The charge of various proteins in solutions with the same pH depends on the amino acid composition, since the dissociation of protein chains leads to the formation of groups with a positive or negative charge. Under the influence of electric field forces, the components of the accelerated system are distributed according to their charge, acquiring the corresponding speed of movement, i.e. electrophoretic separation occurs.
The introduction of electrophoretic “carriers” has led to improved technology and at the same time simplified fractionation. Filter paper, cellulose acetate, various gels (polyacrylamide), agarose, etc. are used as “carriers”. During electrophoresis, along with the separation of particles according to their charges, the so-called “molecular sieve effect” comes into force when the gel structure behaves in relation to ions as a filter. Ions exceeding its porosity do not pass through or pass through very slowly, while smaller ions penetrate faster through the pores of the carrier. Thus, the speed of movement depends not only on the charge of the ion, but also on the size of the gel pores, the shape of the pores, the size of the moving ions, the interaction between the gel matrix and the moving ions (adsorption, etc.).
The history of the creation of electrophoresis began in 1807, when Professor of Moscow State University F. Reis discovered such phenomena as electroosmosis and electrophoresis. However, the practical use of this process in biology and medicine began much later and is associated with the name of Nobel Prize laureate in chemistry Arne Tiselius, who in the 30s of the last century developed the method of electrophoresis in a free liquid and designed a device for the electrophoretic separation and analysis of a mixture of proteins using the free liquid method. or moving boundaries. The main disadvantage of this method was the release of heat when electric current passed through the liquid, which prevented a clear separation of fractions and led to blurring of the boundaries between individual zones. In 1940, D. Philpot proposed the use of columns with a density gradient of buffer solutions, and in the 50s the method was improved and a device for density gradient electrophoresis was created.
However, the method was imperfect, because after turning off the electric current, the zones formed during electrophoresis “blurred.” Subsequent advances in electrophoresis involve the stabilization of zones in a solid support medium. Thus, in 1950, filter paper began to be used as a solid carrier, in 1955 it was proposed to use starch, and already in 1957 Cohn proposed using cellulose acetate films as a solid carrier, which to this day remain one of the most commonly used carriers for clinical studies.
Around this time, a method was developed that used agarose as a base. In 1960, the capillary electrophoresis method was developed, and only in 1989 the first analyzer was created and put into practice, which was based on the capillary electrophoresis method.
The main significance of electrophoresis is the detection of abnormalities in the protein profile and, since the 60s of the last century, serum protein electrophoresis has become a popular screening method for laboratory research. To date, more than 150 individual serum proteins are known, and a significant part of them can be quantified using various modern immunoenzyme, immunochemiluminescent, nephelometric and immunoturbidimetric methods. But despite all the information and evidence of these analyses, they are still largely inaccessible due to their comparative high cost, and also require expensive equipment in the laboratory (nephelometer).
At the same time, typical shifts in the protein composition of blood serum can be determined by a much more accessible electrophoretic method, which also allows “at one glance” to evaluate the overall picture of the protein spectrum and obtain significant diagnostic information. That is why electrophoretic analysis of serum proteins remains a popular screening method of research today, along with a biochemical blood test. For example, in the USA, Japan and some Western European countries, traditions have been preserved for determining the protein fractions of blood serum before conducting a biochemical blood test. However, most often protein electrophoresis is prescribed after biochemical and general clinical blood tests.
Protein electrophoresis helps to identify diseases of the liver and kidneys, the immune system, some malignant neoplasms (multiple myeloma), acute and chronic infections, genetic damage, etc. A number of peculiar electrophoretic “syndromes” are known - typical patterns of electropherograms characteristic of some pathological conditions. Among them are:
1. Monoclonal gammopathies are a collective name for a whole class of diseases in which pathological secretion of abnormal immunoglobulins, altered in chemical structure, molecular weight or immunological properties, occurs by one clone of plasma cells or B-lymphocytes. These immunoglobulins then disrupt the functions of certain organs and systems, for example, the kidneys, which leads to the development of symptoms of the disease.
2. Acute inflammation with activation of the complement system and increased synthesis of acute-phase proteins
(a1-antitrypsin, haptoglobin, fibrinogen, etc.). It is manifested by an increase in the proportion of a1- and a2-globulins and can be confirmed by measuring ESR, studying the concentration of C-reactive protein, fibrinogen (in dynamics) and other acute-phase proteins.
3. Chronic inflammation with increased synthesis of a number of acute-phase proteins, as well as immunoglobulins; manifested by a moderate increase in a2- and b-globulins, an increase in g-globulins and a slight decrease in albumin. Similar deviations can be observed in chronic infections, collagenosis, allergies, autoimmune processes and malignancy.
4. Severe liver diseases are accompanied by a decrease in the synthesis of albumin and a-globulins, which is reflected in electropherograms. In chronic hepatitis and cirrhosis of the liver, both the relative and absolute amount of g-globulins increases (b- and g-fractions can merge due to the accumulation of IgA), and the excess of g-globulins over albumin is a very unfavorable prognostic sign.
5. Nephrotic syndrome is accompanied by an increase in protein filtration in the kidneys and selective proteinuria -
loss in the urine of a large amount of albumin and part of low molecular weight globulins (a1-antitrypsin, transferrin). At the same time, the synthesis of larger proteins of the a2-globulin family (macroglobulin, apo-B) is enhanced in the liver, which accumulate in the blood and form a picture with a significant decrease in albumin and an increase
a2-globulins.
6. Malabsorption or significant loss of proteins is possible both with nephrotic syndrome and with massive burns, Laell's syndrome, pathology of the gastrointestinal tract, etc. In the latter case, the absolute content of total protein and especially albumin decreases, and in the proteinogram the proportion of albumin appears to be reduced with a relatively uniform increase in all globulins. The introduction of protein drugs (immunoglobulins, albumin or blood plasma) during the treatment of patients is immediately reflected in the electrophoretic picture, which makes it possible to monitor the dynamics of losses or excretion of incoming proteins.
7. Severe immunodeficiency of congenital or acquired origin is usually accompanied by a pronounced decrease in the g-globulin fraction. In this case, it is desirable to carry out additional quantitative determination of IgG, IgA and IgM.
Due to the fact that clinical electrophoresis is the “gold standard” for identifying monoclonal gammopathies, I would like to dwell in more detail on the diagnosis of this disease.
Monoclonal gammopathies are a group of malignant neoplasms of B-lymphocyte cells, the morphological substrate of which is cells producing monoclonal immunoglobulin (paraprotein). The number of newly diagnosed cases of multiple myeloma in the United States in 2010, according to the American Cancer Society, was 20,180. The number of deaths from this disease was 10,650. The average age of men at diagnosis was 62 years (75% were over 70 years old), women - 61 years old (79% were over 70 years old). The incidence is 7.8 per 100 thousand population.
In the UK in 2007, there were 4,040 cases of newly diagnosed multiple myeloma. The incidence is 6.5 per 100 thousand population. In the Republic of Belarus (according to the Belarusian Cancer Register (BCR) in 2007, 39,003 cases of diseases with a newly diagnosed diagnosis were registered, which corresponds to an average of 106.9 cases of disease per day.
At the same time, in Russia in 2007, according to the Bulletin of the Russian Cancer Research Center, only 2372 primary cases of multiple myeloma were registered, the incidence was 1.7 per 100 thousand population.
Such a significant difference in the incidence of multiple myeloma in the USA, European countries and Russia is due to the lack in our country of a unified algorithm for diagnosing this disease and screening programs. The scope of diagnostic tests for suspected multiple myeloma recommended by the National Comprehensive Cancer Institute in the USA - the most influential cancer organization in America -
includes the following diagnostic measures:
General blood test (with mandatory blood count calculation).
Detailed biochemical blood test (separation of serum proteins into fractions, creatinine, urea, electrolytes, liver enzymes, beta-2-microglobulin level).
Immunofixation electrophoresis (to determine the type of paraproteinemia).
Urine protein electrophoresis and urine protein immunofixation (24-hour urine) for the diagnosis of light chain disease.

It should be noted that the main importance in these recommendations is given to the method of electrophoresis and immunofixation of blood serum and urine proteins to identify the monoclonal component (paraprotein). The presence of paraprotein in serum or urine is the most common and earliest laboratory manifestation of multiple myeloma. To identify it, protein electrophoresis is carried out, and then
immunofixation electrophoresis of serum and urine. With monoclonal gammopathies, the content of gamma globulins in the serum usually increases, and an acute
peak called M-gradient
(from the word “monoclonal”). The magnitude of the M-gradient reflects the mass of the tumor. The M-gradient is a reliable and sufficiently specific tumor marker for mass examinations. Immunofixation electrophoresis is also indicated for patients in whom there is a high likelihood of multiple myeloma, but conventional electrophoresis did not reveal any additional bands. Light chains (kappa or lambda) in blood serum are detected only by immunofixation, provided that their concentration exceeds 10 norms. Therefore, it is always necessary to perform urine protein electrophoresis simultaneously with serum electrophoresis.
Taking into account the fact that multiple myeloma is a disease that in most cases is diagnosed in people over 50 years of age, as well as the importance of diagnosing this disease at an early subclinical stage (the average duration of the disease in
Stage I - 62 months, stage III - 29 months), in the USA and a number of European countries there are screening programs for people over 50 years of age. The essence of such programs is the annual implementation of a mandatory list of screening laboratory tests, in which electrophoresis of blood serum and urine proteins is included along with a general analysis of blood, urine and biochemical studies.
In some cases, the M-gradient can be observed in practically healthy people. In these cases, we are talking about monoclonal gammopathy of unknown origin. This condition is much more common - in 1% of people over 50 years of age and in almost 10% of people over 75 years of age. This condition does not require treatment, but requires constant monitoring, since in such patients there is a risk of multiple myeloma. Monitoring should include regular examinations with measurement of serum M-gradient (paraprotein) levels by electrophoresis; if the risk of progression is low, the intervals between examinations should be from 6 to 12 months.
In recent years, significant progress has been made in the treatment of this disease. Five-year disease-free survival increased from 24% in 1975 to 35% in 2003. These successes can be explained, on the one hand, by the development of new, modern polychemotherapy regimens, in some cases with high-dose polychemotherapy with bone marrow allotransplantation, and on the other hand, by adequate diagnostics and the development of uniform criteria for assessing the response to therapy, as well as monitoring the level of concentration paraprotein in blood serum and/or urine by electrophoresis to determine residual disease.
Thus, at present, none of the research groups involved in the diagnosis and treatment of multiple myeloma has any doubt about the extreme importance of analyzing the separation of protein fractions of blood serum and immunofixation electrophoresis as the only, most accurate and accessible method for diagnosing and monitoring multiple myelomas.

LITERATURE:

1. Gilmanov A.Zh., Salyakhova R.M. Electrophoresis of serum proteins: modern analysis capabilities, http://med.com.ua
2. Sergeeva N.A./ Electrophoresis in the modern diagnostic process // Klin. lab. diag. - 1999. - No. 2. - P. 25 - 32.
3. Shevchenko O.P., Dolgov V.V., Olefirenko G.A./Electrophoresis in the clinical laboratory. Serum proteins / From: “Triad”, Tver, 2006, 160 p.
4. Jemal, A., Siegel, R., Xu, J. et al. (2010) Cancer statistics, 2010. CA: A Cancer Journal for Clinicians, 60, 277 - 300.
5. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma, Blood. 2008 Mar 1; 111(5):2521-6.
6. Davydov M.I., Aksel E.M./ Statistics of malignant neoplasms in Russia and the CIS countries in 2007// Bulletin of the Russian Cancer Research Center. Volume 20, No. 3 (77), appendix 1,
July - September 2009, 158 pp.
7. National Comprehensive Cancer Network/ Clinical Practice Guidelines in Oncology// Multiple Myeloma, version 1.2011, 52 pg.

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

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

Multiple myeloma is a classic hematological disease that is caused by the proliferation of plasma cells secreting monoclonal immunoglobulin (paraprotein) or its fragments. In most cases, 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 IgA (20%). The remaining approximately 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 may be observed, represented by immunoglobulins of different classes or of 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 PP concentrations in myeloma during therapy should be carried out every 3 months. If the PP content has decreased below the detectable level, it is advisable to repeat the measurement after 6 or 12 months.

Waldenström's macroglobulinemia 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. High concentrations of monoclonal IgM often exceed 30 g/L and lead to increased blood viscosity and a range of clinical manifestations including confusion, blindness, bleeding tendency, heart failure and hypertension. With macroglobulinemia, paraproteinemic polyneuropathy, cold hemolytic anemia and cryoglobulins are often observed. In other types of lymphomas and chronic lymphocytic leukemia, paraproteins of the IgM class are observed in 20% of patients, but the concentration of paraprotein is usually lower than 30 g/l.

Heavy chain disease (Franklin disease) is accompanied by the synthesis of only the IgG-gamma heavy chain, without the accompanying light chain. This extremely rare disease is characterized by swelling of the soft palate and lymphoid infiltration. Also rarely observed is alpha heavy chain disease, which causes chronic diarrhea and malabsorption caused by lymphoid infiltration of the intestinal wall.

During screening examinations, the frequency of detection 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 gammopathies of undetermined significance (MGUS). The paraprotein concentration in MGUS is significantly lower than 30 g/l and usually does not exceed 10–15 g/l. In addition, in MGUS, the paraprotein is detected against the background of polyclonal immunoglobulins, i.e., inhibition of the normal synthesis of other immunoglobulins does not occur. The term “MGUS” indicates 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. When paraproteins are detected in patients under 50 years of age, even more frequent repeat 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, extensive testing is recommended, including electrophoresis of a 24-hour urine sample and immunofixation every 3-6 months, since the risk of malignant transformation is very high. Benign paraproteinemia is distinguished, which is characterized by the persistence of paraprotein without progression to multiple myeloma or another disease over 5 years of observation. With transient paraproteinemia, the paraprotein concentration is usually below 3 g/l.

Indications for prescribing the study:

1. Paraprotein typing.

2. Differential diagnosis of monoclonal gammopathies.

3. Assessing the effectiveness of therapy for myeloma and other gammopathies.

Interpretation of results:

Positively:

Monoclonal gammopathies of unknown significance, benign paraproteinemias;
Multiple myeloma;
Waldenström's macroglobulinemia;
Lymphoma and chronic lymphocytic leukemia;
Heavy chain disease;
Paraproteinemic polyneuropathy;
AL amyloidosis or light chain deposition disease;

Negative:

Normally, the M gradient is not detected in serum.

Description

Determination method

Electrophoresis and immunofixation with pentavalent antiserum with assessment of the M component content using densitometry.

Material under study Blood serum

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Identification and typing of monoclonal paraproteins.

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 precursor stem cells in the bone marrow. Based on structural and functional differences, there are 5 classes of immunoglobulins - IgG, IgA, IgM, IgD, IgE and a number of subclasses. Polyclonal increases in immunoglobulins are a normal response to infections.

Monoclonal gammomapathies are conditions when a clone of plasma cells or B lymphocytes (a population of cells originating from a single precursor B cell) produces an abnormal amount of immunoglobulin. Such conditions may be benign or a manifestation of disease. Monoclonal gammopathies are 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 - 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 antigen specificity.

Immunoglobulin produced by one clone of cells has an identical structure - it represents one class, subclass, and 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, during the electrophoretic separation of serum proteins it migrates in the form of a compact band, 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. In structure, such a monoclonal immunoglobulin can be a polymer, monomer, or fragment of an immunoglobulin molecule (in the case of fragments, these are often light chains, less often heavy chains). Light chains are able to pass through the kidney filter and can be detected by urine electrophoresis.

Identification of monoclonal paraproteins is based on the use of protein electrophoresis. Sometimes fibrinogen and CRP, which migrate into the beta or gamma fractions, can be mistakenly regarded as paraproteins. The immunoglobulin nature of the identified monoclonal component is confirmed by immunofixation of 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 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.

When examining patients using drugs based on monoclonal antibodies (can be used as antitumor therapy, immunosuppressants, etc.), it should be taken into account that at peak concentrations after administration, such drugs can sometimes cause the detection of small abnormal protein bands of an immunoglobulin nature during electrophoresis.

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 lesions of the bones, reduction of other bone marrow cells, which leads to anemia, thrombocytopenia, leukopenia, and inhibits the development of normal clones of plasma cells. Patients may present with localized symptoms of bone pathology (pain, fractures) or nonspecific symptoms (weight loss, anemia, bleeding, recurrent infections, or renal 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 IgA (20%) and about 20% of cases are 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 may be observed, represented by immunoglobulins of different classes or of the same class, but containing light chains of different classes. IgD and IgE myeloma are rare. Determination of paraprotein concentration is used to monitor the effectiveness of treatment for myeloma; such monitoring for myeloma during therapy should be carried out every 3 months. If the paraprotein content has decreased below the detectable level, it is advisable to repeat the measurement after 6 or 12 months.

Monoclonal paraprotein can be detected in a number of non-tumor diseases, in particular, with essential cryoglobulinemia (usually IgM), paraproteinemic chronic polyneuropathy, cold hemolytic anemia, AL amyloidosis of the kidneys (free lambda chains), and internal organs, light chain deposition disease. Serum paraprotein is also observed in Castleman disease (IgM/lambda), POEMS syndrome (polyneuropathy with organ megalia) and lichen myxedema (IgG/kappa).

Literature

1. Andreeva N.E., Balakireva T.V. Paraproteinemic hemoblastoses // Guide to hematology / ed. A. I. Vorobyova. 3rd ed., M., 2003.T. 2, p. 151-184.

2. Berenson J.R Monoclonal gammopathy of undetermined significance: a consensus statement. Br. J. Haematol., 2010, 150(1): 28-38.

Very detailed, large and useful for Myeloma patients

Read a very detailed guide for myeloma patients in PDF format. Guidelines prepared by the International Myeloma Foundation

Myeloma is a tumor of plasma cells that affects
destroying bones.
The outlook for patients with multiple myeloma has recently become significantly
have improved. Modern treatment methods can reduce the manifestations of painful
symptoms of the disease and prolong life by years, and sometimes decades. However, in
Currently, complete recovery from multiple myeloma is almost
impossible and treatment of this disease remains a challenge for
doctors.
What is known about the causes of this disease?
Many scientists and doctors in many countries are researching multiple
myeloma. However, it is still not clear what causes this disease and how
its development can be prevented. However, it must be emphasized that
There are known cases of transmission of multiple myeloma from one person to another.
In other words, multiple myeloma is not contagious. At home the patient has multiple
myeloma does not pose any threat to their loved ones.
Why are the problems associated with multiple myeloma so complex?
. Because there are no known cases of complete cure, treatment can only
reduce the severity of symptoms of the disease and improve quality of life
sick.
. There is not yet sufficient experience with the use of some types of treatment,
to know exactly what will happen to the patient in the future. Moreover, different
The same therapy may have different effects on patients. Your doctors can't
give you no guarantees.
. Almost all types of treatment for multiple myeloma can be accompanied by
severe side effects. Some of them are capable of creating real
threat to life. The patient, his relatives and doctors may have different points of view
to the question of what risk is acceptable. Their opinions may also differ
in relation to acceptable treatment outcome possibilities.
Thus, a patient with multiple myeloma faces a difficult choice. At
When making a decision, doctors will be your main assistants. They can describe
possible methods of combating the disease and after taking it together with you
decisions, prescribe therapy. It is very important that you have an idea of "character"
this disease and had the opportunity to take part in the development of joint
doctors decisions.
Five important questions:
In order to make the right choice, the patient and his family must know:
1. What is multiple myeloma and how does this disease affect
organism?

4. What types of treatment for multiple myeloma can be used.
5. How to choose the therapy that is right for you.
The rest of this guide will be devoted to answering these questions. At the end
A glossary of terms related to multiple myeloma is provided.
1. What is multiple myeloma and what is the impact of this disease
does it have on the body?
Multiple myeloma is a disease of the bone marrow of a tumor nature.
More precisely, it is the result of uncontrolled proliferation of plasma cells. Disease
usually occurs in old age, young people are affected much less frequently.
Plasma cells are an essential part of the human immune system.
The bone marrow is a “factory” for the production of both plasma cells and
other blood cells. In an adult, most bone marrow is found in
pelvic bones, spine, skull, as well as in the long bones of the upper and lower
limbs.
Normally, plasma cells are found in very few cells in the bone marrow.
quantity (less than 5% of all bone marrow cells). As mentioned earlier,
multiple myeloma is accompanied by uncontrolled reproduction
plasma cells. As a result, their content in the bone marrow is significantly
increases (more than 10%, and sometimes up to 90% or more). Because plasma cells
many, they are easily identified when studying bone marrow preparations obtained from
using puncture or trepanobiopsy under a microscope. Tumor plasmatic
the cells are monoclonal, that is, they all come from one cell,
began to multiply uncontrollably.
A plasma cell tumor is a collection of plasma cells and
called plasmacytoma. Plasmacytomas can occur both inside bones
(intramedullary) and outside the bone tissue (extramedullary). Sick
Multiple myeloma may have one or more plasmacytomas. Sick
plasmacytoma do not necessarily have multiple myeloma. There are patients with
solitary plasmacytomas (solitary means the only one), but they have
there is a high risk of developing multiple myeloma in the future.
Multiple myeloma is characterized by several plasmacytomas,
manifested in the form of foci of bone tissue destruction and/or uniform growth
plasma cells in the bone marrow.
Plasma cells produce so-called cytokines (substances
stimulating the growth and/or activity of certain cells) called osteoclasts
activating factor (AAF). OAF stimulates the growth and activity of osteoclasts,
whose activity leads to bone destruction (resorption). If the loss is more than 30%
bone mass, the patient may have severe osteoporosis, or lesions
destruction of bone tissue, which appears as “holes” on x-rays of the bones.
These changes can lead to a decrease in skeletal strength and contribute to the development
fractures. Thus, in most cases, the first signs of multiple
myelomas are bone pain or fractures.
Plasma cell proliferation in bones can disrupt chemical
balance necessary for the normal functioning of the body.
. Plasma cells secrete special proteins called antibodies, which
play an important role in the functioning of the immune system. However, an excess of this protein can
be potentially dangerous, cause kidney damage and lead to impairment
normal blood flow in small vessels. Antibody fragments called lungs
chains or Bence Jones protein can be detected in urine. Therefore multiple
myeloma is often diagnosed after an unusually high concentration is detected
protein in the blood and urine.
. When the bones of a multiple myeloma patient are destroyed by exposure
diseases, large amounts of calcium are released, which can lead to
increasing its content in the blood. This condition is called "hypercalcemia."
Uncontrolled hypercalcemia often causes life-threatening complications,
including renal failure and impaired consciousness.
. Excess plasma cells in the bones and calcium and protein in the blood can lead to
a decrease in the number of erythrocytes (red blood cells), that is, anemia and
cause weakness in the patient. It is typical for patients with multiple myeloma
suppression of immune system function, resulting in increased susceptibility
to infectious diseases. In addition, the course of the disease is sometimes
accompanied by a decrease in the concentration of platelets in the blood and/or a decrease in their
functional activity, this can lead to frequent bleeding.
2. How do doctors confirm the diagnosis of multiple myeloma and how do they
discover that the disease is progressing?
Multiple myeloma may be suspected in a person with changes in blood tests
and urine, in the presence of bone pain and pathological fractures. Diagnosis
confirmed if the patient has two of the four signs listed below.
. When examining bone marrow obtained by puncture, among all cells
plasma cells make up at least 10%.
. X-ray photographs of bones reveal foci of bone tissue destruction (according to
at least three in different bones.
. Blood and urine tests reveal abnormally high levels of antibodies
(immunoglobulins) or Bence Jones protein (this test is called electrophoresis
proteins).
. A biopsy of bones or other tissues reveals tumor clusters
plasma cells.
Solitary plasmacytoma is diagnosed if:
. A tumor biopsy reveals a single focus of plasmacytoma.
. Other foci of plasma cell proliferation, outside the found tumor,
cannot be detected.
Patients with solitary plasmacytoma may also have an M-gradient in the blood or
in urine. The diagnosis can be considered finally confirmed if, after removal
tumor (by surgery or with radiation therapy) the M-gradient disappears.
Solitary plasmacytoma is usually an early stage of multiple
myelomas. It is known that the majority of people who had solitary plasmacytoma, in
eventually developed multiple myeloma. The risk of transformation is especially
high if solitary plasmacytoma was found in bone tissue. Predict
the length of time required for the transformation of solitary plasmacytoma into
multiple myeloma is currently not possible.
Some people who have an M-gradient in their blood or urine
they feel absolutely normal. This condition is called "monoclonal"
gammopathy." A significant proportion of these patients eventually develop
multiple myeloma, but this condition does not require any treatment.
When a patient is diagnosed with multiple myeloma, it is important to evaluate
main characteristics of the disease. Doctors in this situation are looking for answers to two
main issues.
How large is the cell mass? Cell mass indicators are
percentage of plasma cells in the bone marrow, severity
bone lesions and the amount of protein in the blood and urine. Cell mass is
an indicator of how long ago the disease developed in the patient’s body. All in all,
the greater the cell mass, the more altered the normal biochemical
body balance and immune system function. The greater the cell mass, the
greater risk of developing dangerous complications of the disease. the more
the need for immediate initiation of therapy to reduce cell mass
myelomas.
How aggressive is the disease? Or more simply put, how quickly
plasma cells multiply. The number of cells increases
during a process called mitosis. The essence of mitosis is duplication
chromosomes of the cell (its genetic information) which then evenly
distributed among two new ones formed as a result of the division of the mother
cells. In industrialized countries, the “aggressiveness” of multiple
myelomas are measured using a method called the "label index". Index
labels shows what percentage of myeloma cells are in the mitosis phase (then
is in the process of division). The higher the label index, the faster it increases
number of plasma cells. Its assessment is important because multiple
myeloma with a lower cell mass but a high label index usually progresses
more aggressive than a disease with a higher cell mass (with more
severity of symptoms) but with a lower label index. High
the aggressiveness of multiple myeloma is another argument in favor of
to begin chemotherapy immediately. Such patients require more
close observation even if the multiple myeloma cell mass
(the severity of symptoms) is not great. Unfortunately, in our country we do not have
ability to measure the mark index. However, to assess “aggressiveness”
multiple myeloma, you can use the albumin concentration and so on
called C-reactive protein in the blood serum.
The answers to these two questions are also important because they allow us to estimate the likelihood
success with various treatment methods. For example, some therapeutic techniques
work better for more aggressive myeloma. Evaluation of both parameters (cellular
weight and aggressiveness of the disease) is important for assessing the patient’s treatment prospects.
If these indicators decrease during therapy, this is in favor of
that the treatment gives a positive result.
There are many indicators that allow doctors to judge the likelihood
the patient's response to the planned treatment and the likelihood of disease progression.
Let's give some of them as an example.
. Type of plasma cells depending on the protein they secrete
(IgG, IgA, IgD, IgE, immunoglobulin heavy chains, immunoglobulin light chains
"kappa" or "lambda").
. The concentration in the blood of various cytokines - substances synthesized by human
body and capable of influencing the functioning of various cells
(interleukin 6, interleukin 2, beta-2 microglobulin, C-reactive protein).
. Response to treatment, or in other words, do they go away during treatment?
symptoms of the disease and whether laboratory values change,
characteristic of myeloma (concentration of M-gradient in the blood).
In some cases, the assessment of some indicators provides additional information
about the aggressiveness of multiple myeloma, others say nothing about the speed
proliferation of plasma cells, but based on clinical practice allow
make predictions for the future.
Thus, before choosing treatment, a patient with multiple myeloma should
undergo a large number of different studies to assess character
of your disease, its aggressiveness, studying prognosis factors, and the degree of impairment
physiological functions of the body. Doctors do not prescribe tests out of "idleness"
curiosity."
3. What effect should be expected from the treatment?
If the disease is completely incurable, then what are your doctors trying to achieve? Therapy
multiple myeloma is performed to achieve 4 goals.
. Stabilization - counteracting further progression of disease manifestations,
leading to disruption of basic biochemical processes, weakening
functions of the immune system and life-threatening for the patient. In other words, on
treatment stops the steady progression of the disease, characteristic of its
natural course.
. Temporary “mitigation” of the disease - reduction of painful symptoms that cause
a feeling of discomfort and improvement in basic body functions.
. Induction of remission - a significant reduction in the manifestations of the main symptoms
disease, temporary elimination of all visible signs of multiple myeloma.
. “Recovery” or achieving permanent remission (extremely rare).
In other words, treatment is prescribed to improve the patient’s well-being and
normalize the functions of his body. Over a certain period of time it may
reduce the severity of symptoms of the disease or even stop the natural
course of the disease. Remission can last from several months to
decades. Some patients who are in remission die from causes not
associated with multiple myeloma. Modern experimental techniques
treatments set themselves the task of completely curing patients, but there is no evidence
There is currently no such possibility.
4. What types of treatment for multiple myeloma can be used?
Chemotherapy kills malignant plasma cells and is done to
achieving remission or even cure of the patient. Its basis is
cytostatic antitumor drugs prescribed by injection
or in tablet form.
The most common combination used to treat multiple myeloma is
melphalan (alkeran) and prednisolone. In addition, the patient may be prescribed
vincristine, cyclophosphamide, carmustine (BCNU) and doxorubicin (Adriamycin). Sometimes they
used in combination with melphalan and prednisolone. Prednisolone may
replaced by dexamethasone. Combinations of cytostatics, in some cases, may be
more effective than a single chemotherapy drug. Chemotherapy courses are usually
are called an abbreviation of the first letters of the Latin names included in them
drugs. For example: MR is melphalan (alkeran) and prednisolone, VBMCP is
vincristine, BCNU, melphalan, cyclophosphamide and prednisolone, VAD - vincristine,
adriamycin and dexamethasone and so on.
The choice of chemotherapy course may depend on many factors including age,
stage of the disease, preservation of kidney function. Usually patients are younger than 65-70 years old
able to withstand large doses of antitumor drugs. Duration
One course of chemotherapy is approximately one month. Chemotherapy may
be carried out in a hospital or outpatient setting (that is, chemotherapy for some patients
can be taken at home). Sometimes outpatient treatment is preferable
since in a hospital there is a risk of infection with dangerous “nosocomial”
infections.
The course of chemotherapy includes two stages. At first, the patient receives
drugs that act on both myeloma and normal cells
hematopoiesis and cells of the immune system, leading to inhibition of their normal
functions. At the second stage, the violations caused by the intake are restored.
chemotherapy. By killing tumor cells, chemotherapy can reduce symptoms
symptoms of the disease, such as anemia, hypercalcemia, bone destruction,
the content of abnormal proteins in the blood and urine. According to the degree of concentration reduction
plasma cells in the bone marrow and pathological monoclonal protein in
blood and urine of the patient, one can judge the effect of chemotherapy. Necessary
especially emphasize that treatment is considered effective even in cases where complete
remission has not been achieved.
Radiation therapy is usually administered locally to areas of bone destruction,
causing pain and/or posing a risk of dangerous fractures. Radiation
can be used for final “cleansing” of plasma cells after
surgical removal of plasmacytoma. The affected area is exposed
a certain, controlled dose of radiation. Radiation therapy kills plasma cells
cells faster than chemotherapy and is accompanied by fewer side effects
effects. Therefore, it is usually used to quickly relieve pain and for
effects on large foci of destruction in bone tissue, as well as in patients not
able to tolerate chemotherapy. It is also possible to combine radiation and
chemotherapy. Radiation is usually given five days a week for several
weeks or months. During the period of radiation therapy, the patient may be
Houses. The chemotherapy plan includes the dose of radiation, the area to be irradiated, and
duration of treatment.
Interferon-. usually used to maintain the effect of the performed
chemotherapy or bone marrow transplantation. It helps prolong the condition
remission. It is believed to be able to limit the proliferation of plasma cells.
As a result of this, interferon-. capable of delaying (but not preventing)
the onset of relapse of the disease. Interferon is prescribed. usually in outpatient settings
conditions 3 times a week in the form of subcutaneous or intramuscular injections.
Transplantation of bone marrow or peripheral blood stem cells into
is currently undergoing clinical trials as a possible
alternatives to “standard” chemotherapy. There are hopes associated with this method
the possibility of curing patients with multiple myeloma, although to date
no direct evidence of this has been obtained. The transplantation is based on high-dose
chemotherapy is sometimes combined with total body irradiation. This is the impact
so strong that it can completely destroy the hematopoietic tissue, without which
human life is impossible. Stem cells transplanted into a patient replace
died protecting the patient from fatal complications. So the value
transplantation is that it allows such powerful therapy, the implementation of which in
under normal circumstances it would be too risky. There is hope that together with
bone marrow will destroy all diseased cells. Bone marrow for
transplantation is taken or from a donor selected according to special characteristics
(allogeneic transplantation), or from the patient himself (autologous transplantation).
When the patient's own bone marrow is used for transplantation, before administering
they are often cleared of tumor cells using special drugs or
antibodies. Before bone marrow or peripheral stem cell transplantation
Several preparatory courses of chemotherapy are carried out. The procedure itself requires
stay of the patient for several weeks or months in conditions
specialized department, followed by a period during which life
The patient's activity should be limited. Transplantation is the most
aggressive, of the currently existing types of treatment for multiple
myeloma, and therefore its implementation is accompanied by a high risk of serious
complications. Bone marrow and stem cell transplantation is an object
close attention of researchers trying to use it to discover new
opportunities to increase the life expectancy of patients with multiple
myeloma, and clarifying its place in the arsenal of treatments for this severe
diseases.
Stem cell harvesting is the procedure of isolating stem cells from
blood for the purpose of their subsequent use for transplantation.
Plasmapheresis is used in patients with multiple myeloma when the concentration
protein in their blood reaches alarmingly high levels and requires rapid reduction.
The procedure involves drawing blood using a special device, removing
protein and the return of other blood components to the body.
Other concomitant therapy includes drugs used to control
hypercalcemia, bone destruction, pain and infection. Bisphosphonates (eg
Aredia) can significantly reduce the severity of bone damage and prevent
hypercalcemia in multiple myeloma. Antibiotics may play a role in
prevention and treatment of infectious complications. Erythropoietin is prescribed with
the goal of reducing the severity of anemia and associated symptoms (for example
weaknesses). Surgical methods can be used to remove tumors,
restoring bones after fractures or reducing the severity of pain.
Other appointments. It is advisable that, without the permission of the attending physician, the patient
multiple myeloma did not take any medications. So uncontrolled reception
non-narcotic analgesics (brufen, diclofenac sodium or voltaren, indomethacin
etc.) in patients with impaired renal function, can lead to a deepening of the renal
insufficiency.
5. How to choose the therapy that is right for you?
The question of choosing treatment tactics arises during the diagnosis of the disease and
with the development of relapse. It is quite natural that at the first moment you find yourself
shocked by the new diagnosis, and your knowledge regarding the disease and its methods
treatments are very limited. Your doctors understand this well, they will help you take
solution and try to reduce your worries.
When you need to make a decision about how to be treated, the first rule is
stop and think. Of course, there are life-threatening conditions
requiring immediate intervention, but to understand other issues you
you have enough time. In addition, it must be remembered that
Some immediate decisions need to be made taking into account plans for the future.
For example, if autologous stem cell transplantation is planned, the use of
Some drugs (for example alkeran) are extremely undesirable.
This does not mean that patients themselves determine their treatment. However, it is important
Find out from your doctor what actions need to be taken immediately, and with
which ones you can wait for. When the situation allows, before starting therapy, consider
advantages and disadvantages of various treatment programs.
First, understand the main goals of the proposed treatment. Usually,
any therapeutic program includes many elements aimed at
to solve various problems. Some of them require immediate action and
are aimed at eliminating the most dangerous symptoms. Exercising others can
be put aside and you will have enough time to think.
It must be remembered that there is no absolute one-size-fits-all
treatment method for multiple myeloma. Even bone marrow transplantation or
peripheral blood stem cells are not necessarily indicated for young and well
feeling sick, although this procedure is relatively “easy” to perform in
this category of patients. Some patients are in the early stages of developmental disease
They only need the supervision of a hematologist. Carrying out standard
chemotherapy programs aimed at achieving remission cannot
guarantee you the expected result. Doctors know the likelihood of success when
using various treatment methods and can apply special
diagnostic tests to select the programs that are best for you
way. Everything that has been said about standard chemotherapy equally applies to
transplantation, the goal of which is recovery.
The time frame within which decisions regarding major issues must be made
aspects of the treatment of multiple myeloma, we present in the following table.
EFFECT OF TREATMENT GOAL EXAMPLES DEADLINE FOR DECISION MAKING

STABILIZATION Counteracting life-threatening biochemical disturbances
homeostasis and immune system caused by myeloma
*
Plasmapheresis to reduce blood viscosity
*
Hemodialysis when kidney function is seriously impaired
*
Treatment of hypercalcemia (Aredia), may include chemotherapy
.... ... ...
TEMPORARY “ALLIFIATION” OF DISEASE Reduced discomfort, increased ability
perform normal functions
*
Radiation to stop bone destruction
*
Erythropoietin to reduce anemia
*
Orthopedic surgeries to restore bone function
... ... ......
INDUCTION OF REMISSION significant reduction in the manifestations of the main symptoms, temporary elimination of all manifestations of myeloma
*
Chemotherapy affects myeloma cells throughout the body
*
Radiation therapy affects myeloma cells in the irradiated area
...... ...
RECOVERY Permanent remission (currently
practically unattainable)

Bone marrow transplantation, which makes it possible to endure very high doses of chemotherapy
......
What should you talk to your doctor about?
Below is a list of questions we recommend you ask first.
. Ask for a general treatment plan.
. What problems are planned to be solved during therapy?
. How long will it take for treatment?
. How often do you need to visit a medical facility? Is it necessary to undergo treatment?
hospital?
. What complications may accompany treatment. How the disease and its therapy affect
on the patient's ability to perform basic functions (for example, work,
serve yourself, etc.). How people feel before treatment, during treatment
and after it ends? What do other multiple myeloma patients look like?
What is the total duration of the course of therapy? What is the duration of the period
recovery after treatment?
. What does a surveillance program for a patient with multiple myeloma include?
. How much does it cost? And to what extent can expenses be offset?
insurance system?
Find out how the treatment proposed to you worked for other patients in similar situations.
situations. The effectiveness of treatment can be assessed using various parameters.
Try to get answers to the following questions.
. What experience do you have with the treatment proposed to you? How many patients
received such therapy? How long did the doctors monitor them?
. What is the probability (chance) of achieving complete or partial remission? Which
What factors contribute to the best and worst prognosis?
. What actions can be taken in case of relapse of the disease?
. What can be done to reduce bone pain, treat pathological
fractures, anemia, general weakness, hypercalcemia? What signs indicate
is the prognosis good or bad in these situations?
. What is the life expectancy of patients receiving your planned
treatment?
Complications of therapy. Used to treat multiple myeloma
potent drugs whose action is aimed at
destruction of tumor cells and/or those capable of changing the biochemical balance in
body. Therefore, their use may be accompanied by severe side effects.
phenomena. Some may appear already during the treatment itself, others appear
after its completion.
Cytostatic drugs can kill not only “patients” but also
"healthy" cells of the patient. Therefore, patients receiving them should be under
special supervision to avoid or minimize its side effects.
Complications of chemotherapy depend on the type of drug, its dose and duration
reception. Those most affected by the effects of anticancer drugs are
rapidly dividing cells. Among the normal cells of the human body, these include
includes bone marrow precursors of blood cells, cells covering
the inner surface of the mouth and intestines, as well as the cells of the hair follicles. IN
as a result of this, the patient may develop hair loss, stomatitis (defeat
oral mucosa), decreased resistance to infections (in
consequence of a decrease in the number of leukocytes in the blood), weakness appears (due to
decrease in the number of red blood cells in the blood) and increased bleeding (due to
decrease in the number of platelets in the blood). Loss of appetite, nausea and vomiting mainly
are not caused by damage to the cells of the gastrointestinal tract, but are
a consequence of the effect of chemotherapy on special centers in the brain. This effect
temporary, and it can be eliminated with the help of special medications
drugs, such as Novaban.
In addition, some antitumor drugs can have
adverse effects on certain internal organs, such as the heart
(Adriamycin) and kidneys (cyclophosphamide). Thus, doctors every time have to
find a balance between the desired antitumor effect of drugs and their
side effects.
You are advised to ask the following questions about side effects:
treatment.
. What complications do patients experience as a result of treatment? When they
are they developing? How often do they occur (in what percentage of patients)?
. How dangerous are the side effects of the therapy? Do they represent
life threatening? Will they be accompanied by pain? What are their
duration?
. Is there a treatment for these complications? Does it have its complications?
Perhaps one of the most important is the question of the existence
alternative techniques. In almost every case, different
treatment approaches. In this regard, you are advised to obtain answers to
the following questions.
. What alternative treatments can be used?
. What are their positive and negative sides?
. What is more profitable in my case, immediate start of treatment or observation without
chemotherapy?
It must be remembered that making a decision takes time.
In order to make a choice, you will need information about your new
disease. Most of what is known about multiple myeloma has been written
doctors and scientists for doctors and scientists like them. Therefore, if you and yours
relatives do not have special training to understand the medical literature,
dedicated to this problem, it will not be easy for you.
Therefore, doctors are forced to bear the heavy burden of teaching their patients.
Your doctors will provide advice and explanations to you and your loved ones throughout
treatment period. Some patients are very curious and want to
discuss all issues related to their disease, its treatment and prognosis. Other
depressed, and interested only in what awaits them tomorrow.
Most doctors sense this and change their approach depending on
the patient's wishes. You can speed up and simplify this process if you clearly express your
desire regarding how deeply you want to understand problems,
related to the treatment of multiple myeloma, and participate in decision-making.
Remember, the choice of treatment is very important for the quality and length of life
patient with multiple myeloma. Remember, before making a final decision,
It’s good to know the opinions of various experts; this will not spoil the relationship with your
doctor.
Since multiple myeloma is a rare disease, the number of specialists
people who understand this problem and the number of medical centers where this is treated
pathology is quite small. Doctors know this and will recommend you the right specialists.
It is quite possible that the patient, while continuing to be treated under the supervision of his
doctors, receives advice from specialists from some scientific center,
studying multiple myeloma.
Making a decision will require ingenuity, careful consideration of all
sides of the issue, serious thought and courage. However, it seems important that
the patient and his relatives had sufficient
information about the progress of treatment, and understood its goals and capabilities.