The role of electrophoresis in the diagnosis of multiple myeloma. Archive on myeloma M urine gradient in vitro

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), quantitative assessment of M protein

Laboratory diagnostics
: proteins and amino acids.

Indications

Paraprotein typing.
Differential diagnosis of monoclonal gammopathies.
Evaluation of the effectiveness of therapy for myeloma and other gammopathies

Preparation
It is preferable to wait 4 hours after your last meal; there are no mandatory requirements.

Description
Identification 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 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 gamma fraction, 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.

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% 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 myeloma treatment; 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.

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.

Monoclonal paraprotein can be detected in a number of non-tumor diseases, in particular, in 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).

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, it is recommended to carry out an extensive examination, 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 preservation 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.

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

Bence Jones protein- a tumor marker that is used to diagnose multiple myeloma (plasma cell tumor). Bence Jones protein consists of free light chains of immunoglobulins. In healthy people, a small amount of free light chains is constantly produced, 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 tubules without ending up in the final urine. In monoclonal gammopathies, the production of abnormal immunoglobulins by the malignant clone of plasma cells is observed. This leads to an excess of free light chains in the primary urine and the appearance of 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).

Determination of Bence Jones protein in urine reflects kidney damage - tubular atrophy, severe sclerosis of the renal interstitium. Damage is enhanced by predisposing factors (dehydration, hypercalcemia, use of radiocontrast agents, certain medications), which can lead to renal failure.

Compound:

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

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 an electric field. 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.

Description

Determination method

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

Material under study Blood serum

Home visit available

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.

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 myeloma treatment; 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.

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 should 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 labeling 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 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 “SOFTENING” THE DISEASE Reducing discomfort, increasing 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
next 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 your
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.