The role of electrophoresis in the diagnosis of multiple myeloma. Myeloma Archive 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), M-protein quantification

Laboratory diagnostics
: proteins and amino acids.

Indications

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

Preparation
It is preferable to withstand 4 hours after the last meal, there are no mandatory requirements.

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

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

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

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

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

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

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

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

Monoclonal paraprotein can be 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. Paraprotein in the blood serum is also noted in Castleman's disease (IgM / lambda), POEMS syndrome (polyneuropathy with organ megalia) and myxedematous lichen (IgG / kappa).

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

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

Bence Jones protein- a tumor marker that is used to diagnose multiple myeloma (plasma cell tumors). Bence-Jones protein consists of free light chains of immunoglobulins. In healthy individuals, a small number of free light chains are continuously 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 tubule without entering the final urine. In monoclonal gammopathy, there is production of abnormal immunoglobulins by a malignant clone of plasma cells. This results in an excess of free light chains in the primary urine and Bence-Jones protein in the final urine.

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

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

Compound:

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

The basic principle of the electrophoretic research method is that the molecules in solution, which have an electric charge, are displaced towards an 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 rate of displacement largely depend on the pH of the medium 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 the 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 to the simplification of fractionation. Filter paper, cellulose acetate, various gels (polyacrylamide), agarose, etc. are used as "carriers". At the same time, 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 like a filter with respect to ions. Ions that exceed its porosity do not pass or pass 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 the 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 the Nobel Prize winner in chemistry Arne Tiselius, who in the 30s of the last century developed the free liquid electrophoresis method and designed a device for electrophoretic separation and analysis of a mixture of proteins using the free or moving boundaries method. The main disadvantage of this method was the release of heat during the passage of an electric current 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 1950s the method was improved and a device for electrophoresis in a density gradient was created.
However, the method was not perfect, because after the electric current was turned off, the zones formed during electrophoresis “blurred”. Subsequent advances in electrophoresis are associated with the stabilization of zones in a solid supporting medium. So, 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 the use of cellulose acetate films as a solid carrier, which to this day remain one of the most commonly used carriers in clinical studies.
Around this time, a method was developed that used agarose as a base. In 1960, the method of capillary electrophoresis was developed, and only in 1989 was the first analyzer created and put into practice, which was based on the method of capillary electrophoresis.
The main significance of electrophoresis is the detection of protein profile anomalies and, since the 1960s, serum protein electrophoresis has become a popular laboratory screening method. To date, more than 150 individual serum proteins are already known, and a significant part of them can be quantified using various modern enzyme immunoassay, immunochemiluminescent, nephelometric and immunoturbidimetric methods. But with all the informativeness and evidence of these analyzes, they are still largely inaccessible due to the comparative high cost, and also require expensive equipment (nephelometer) in the laboratory.
At the same time, typical shifts in the protein composition of the blood serum can be determined by a much more accessible electrophoretic method, which also allows one to assess the overall picture of the protein spectrum and obtain significant diagnostic information “at a glance”. That is why the electrophoretic analysis of serum proteins remains today, along with a biochemical blood test, a popular screening research method. For example, in the United States, Japan and some countries of Western Europe, the traditions of determining the protein fractions of blood serum before conducting a biochemical blood test have been preserved. 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 breakdowns, etc. A number of peculiar electrophoretic "syndromes" are known - typical patterns of electrophoregrams characteristic of some pathological conditions. Among them are:
1. Monoclonal gammopathy is a collective name for a whole class of diseases in which there is a pathological secretion of abnormal, changed in chemical structure, molecular weight or immunological properties of immunoglobulins by one clone of plasma cells or B-lymphocytes. These immunoglobulins then disrupt the functions of certain organs and systems, such as 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 the ESR, examining 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 electrophoregrams. In chronic hepatitis and cirrhosis of the liver, both the relative and absolute amounts of g-globulins increase (b- and g-fractions can merge due to the accumulation of IgA), and the excess of g-globulins over albumins is a very unfavorable prognostic sign.
5. Nephrotic syndrome is accompanied by an increase in protein filtration in the kidneys and selective proteinuria -
loss with 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) increases in the liver, which accumulate in the blood and form a picture with a significant decrease in albumin and an increase in
a2-globulins.
6. Malabsorption or a significant loss of proteins is possible both with nephrotic syndrome and with massive burns, Laella's syndrome, pathology of the gastrointestinal tract, etc. In the latter case, the absolute content of total protein and especially albumin decreases, and the proteinogram shows a decrease in the proportion of albumin with a relatively uniform increase in all globulins. The introduction of protein preparations (immunoglobulins, albumin or blood plasma) during the treatment of patients is immediately reflected in the electrophoretic picture, which allows you to monitor the dynamics of loss 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 conduct an additional quantitative determination of IgG, IgA and IgM.
Due to the fact that clinical electrophoresis is the "gold standard" for the detection of monoclonal gammopathy, I would like to dwell on the diagnosis of this disease in more detail.
Monoclonal gammopathy is a group of malignant neoplasms from cells of the B-lymphocyte series, the morphological substrate of which are 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 the time of diagnosis was 62 years (75% were over 70 years old), women - 61 years (79% were over 70 years old). Morbidity - 7.8 per 100 thousand population.
In the UK in 2007, there were 4040 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 Registry (BCR) in 2007, 39,003 cases of diseases with a first diagnosis were registered, which corresponds to an average registration of 106.9 cases of diseases per day.
At the same time, in Russia in 2007, according to the Bulletin of the Russian Cancer Research Center of the Russian Academy of Medical Sciences, only 2372 primary cases of multiple myeloma were registered, the incidence was 1.7 per 100 thousand of the population.
Such a significant difference in the incidence of multiple myeloma in the United States, European countries and Russia is due to the lack of a single algorithm for diagnosing this disease and screening programs in our country. The volume of diagnostic tests for suspected multiple myeloma, recommended by the National Cancer Institute in the United States (National Comprehensive Cancer) - the most influential cancer organization in America -
includes the following diagnostic measures:
Complete blood count (with obligatory calculation of the blood formula).
Detailed biochemical blood test (separation of blood serum proteins into fractions, creatinine, urea, electrolytes, liver enzymes, beta-2-microglobulin level).
Immunofixation electrophoresis (to determine the type of paraproteinemia).
Urinary protein electrophoresis and urinary protein immunofixation (daily urine) for the diagnosis of light chain disease.

It should be noted that the main significance in these recommendations is given to the method of electrophoresis and immunofixation of proteins in blood serum and urine for the detection of a monoclonal component (paraprotein). The presence of paraprotein in serum or urine is the most common and earliest laboratory manifestation of multiple myeloma. To detect it, protein electrophoresis is carried out, and then -
immunofixation electrophoresis of serum and urine. With monoclonal gammopathy, the content of gamma globulins in serum usually increases, and an acute
a peak called the M-gradient
(from the word "monoclonal"). The value 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 in patients who are highly likely to have 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, urine protein electrophoresis must always be performed 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 at
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 old. The essence of such programs lies in the annual implementation of a mandatory list of screening laboratory tests, in which electrophoresis of blood serum and urine proteins is included in one row with a general blood test, urine analysis 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 old and in almost 10% over 75 years old. This condition does not require treatment, but requires constant monitoring, since such patients are likely to develop multiple myeloma. Monitoring should include regular examinations with the measurement of the level of M-gradient (paraprotein) in serum by electrophoresis; at low risk of progression, intervals between examinations should be 6 to 12 months.
Significant progress has been made in the treatment of this disease in recent years. The five-year relapse-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 regimens of polychemotherapy, 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 paraprotein concentration in the blood serum and/or urine by electrophoresis to determine the residual disease.
Thus, at present, none of the research groups involved in the diagnosis and treatment of multiple myeloma has any doubts about the extreme importance of analyzing the separation of protein fractions of blood serum and performing immunofixation electrophoresis as the only, most accurate and affordable method for diagnosing and monitoring multiple myeloma.

LITERATURE:

1. Gilmanov A.Zh., Salyakhova R.M. Serum protein electrophoresis: modern possibilities of analysis, http://med.com.ua
2. Sergeeva N.A./ Electrophoresis in the modern diagnostic process // Klin. lab. diag. - 1999. - No. 2. - S. 25 - 32.
3. Shevchenko O.P., Dolgov V.V., Olefirenko G.A./Electrophoresis in the clinical laboratory. Serum proteins / Published by: "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// Vestnik RONTS. Volume 20, No. 3 (77), appendix 1,
July - September 2009, 158 p.
7. National Comprehensive Cancer Network/ Clinical Practice Guidelines in Oncology// Multiple Myeloma, version 1.2011, 52 pg.

Description

Method of determination

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

Material under study 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 progenitor stem cells in the bone marrow. According to structural and functional differences, 5 classes of immunoglobulins are distinguished - IgG, IgA, IgM, IgD, IgE and a number of subclasses. A polyclonal increase in immunoglobulins is a normal response to infections.

The detection of monoclonal paraproteins is based on the use of protein electrophoresis. Sometimes fibrinogen and CRP that migrate into beta or gamma fractions can be mistakenly regarded as paraproteins. The immunoglobulin nature of the identified monoclonal component is confirmed by immunofixation of the separated proteins with a specific polyvalent precipitating antiserum directed against immunoglobulins (test No. 4050). When confirming the presence of monoclonal immunoglobulin, densitometry is performed and its quantitative content is determined. Full identification (typing) of the monoclonal component requires a detailed study using electrophoresis and immunofixation with a detailed panel of antisera against IgG, IgA, IgM, kappa and lambda chains (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 borne in mind that at peak concentrations after administration, such drugs can sometimes cause the detection of small abnormal bands of an immunoglobulin protein 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 bone lesions, reduction of other bone marrow cells, which leads to anemia, thrombocytopenia, leukopenia, inhibits the development of normal clones of plasma cells. Patients may present with local symptoms of bone disease (pain, fractures) or non-specific symptoms (weight loss, anemia, bleeding, repeated infections, or kidney failure). In most patients at the time of diagnosis, the paraprotein concentration exceeds 25 g/l. With myeloma, the paraprotein in the blood serum is most often represented by IgG (60%), less often by IgA (20%), and about 20% of cases are due to Bence-Jones myeloma, associated with the production of free light chains kappa or lambda (20%), which can be detected in urine. Sometimes in myeloma, a biclonal paraprotein can be observed, represented by immunoglobulins of different classes or of the same class, but containing light chains of different classes. Rarely marked IgD and IgE myeloma. Determination of paraprotein concentration is used to monitor the effectiveness of myeloma treatment, such monitoring in myeloma during therapy should be carried out every 3 months. If the paraprotein content has decreased below the detectable level, it is advisable to re-measure after 6 or 12 months.

Literature

1. Andreeva N.E., Balakireva T.V. Paraproteinemic hemoblastosis // Guide to hematology / ed. A. I. Vorobiev. 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 patients with myeloma in PDF format. Guidelines prepared by the International Myeloma Foundation

Myeloma is a tumor derived from plasma cells that affects and
destroying bones.
The outlook for patients with multiple myeloma has recently been significantly
improved. Modern methods of treatment can reduce the manifestations of painful
symptoms of the disease and prolong life for years, and sometimes decades. However, also in
Currently, a full recovery from multiple myeloma is practically
impossible and the treatment of this disease is still a difficult task for
doctors.
What is known about the causes of this disease?
Many scientists and physicians in many countries are investigating multiple
myeloma. However, it is still not clear what causes this disease and how
development can be prevented. However, it must be emphasized that it is not
known cases of transmission of multiple myeloma from one person to another.
In other words, multiple myeloma is not contagious. Multiple sick home
myeloma poses no threat to their loved ones.
Why are the problems associated with multiple myeloma so complex?
. Because there are no known cases of a complete cure, treatment can only
reduce the severity of symptoms of the disease, and improve the quality of life
sick.
. Sufficient experience has not yet been accumulated on the use of some types of treatment,
to know exactly what will happen to the patient in the future. Moreover, different
patients, the same therapy may have a different effect. Your doctors cannot
give you no guarantees.
. Almost all treatments for multiple myeloma can be accompanied by
severe side effects. Some of them are able to create real
life threat. 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 outcomes.
Thus, a patient with multiple myeloma faces a difficult choice. At
making a decision, doctors will be your main assistants. They can describe
possible methods of dealing with the disease and after taking with you jointly
decisions, prescribe therapy. It is very important that you have an idea of \u200b\u200b"character"
this disease and had the opportunity to take part in the development of a joint
decision doctors.
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 it affect
organism?

4. What types of treatment for multiple myeloma can be applied.
5. How to choose the right therapy for you.
The rest of this guide will focus on 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
has on the body?
Multiple myeloma is a malignant disease of the bone marrow.
More precisely - the result of uncontrolled reproduction of plasma cells. Disease
usually occurs in the elderly, 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 of the bone marrow is contained in
pelvic bones, in the spine, skull, as well as in the long bones of the upper and lower
limbs.
Normally, plasma cells are found in the bone marrow in a very small
amount (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 detected in the study of bone marrow preparations obtained with
using a puncture or trepanobiopsy under a microscope. Tumor plasma
cells are monoclonal, meaning they all come from the same cell,
began to multiply uncontrollably.
A plasma cell tumor is a collection of plasma cells and
called a 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. Patients meet with
solitary plasmacytomas (solitary means the only one), but they have
there is a high risk of multiple myeloma in the future.
Multiple myeloma is characterized by multiple plasmacytomas,
manifested in the form of foci of destruction of bone tissue 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 (AFF). OAF stimulates the growth and activity of osteoclasts,
activity of which leads to the destruction of bones (resorption). With a loss of more than 30%
mass of bone tissue, the patient may have severe osteoporosis, or foci
destruction of bone tissue, which looks like “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.
Proliferation of plasma cells in bones can disrupt the chemical
balance necessary for the normal functioning of the body.
. Plasma cells secrete special proteins called antibodies that
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 impaired
normal blood flow in small vessels. Fragments of antibodies called lungs
chains or Bence-Jones protein can be determined in the urine. Therefore, multiple
myeloma is often identified after finding an unusually high concentration
protein in blood and urine.
. When the bones of a multiple myeloma patient are destroyed by exposure to
diseases, large amounts of calcium are released, which can lead to
increase in its content in the blood. This condition is called "hypercalcemia".
Uncontrolled hypercalcemia often causes life-threatening complications,
including renal failure and impaired consciousness.
. An excess of plasma cells in the bones, calcium and protein in the blood can lead to
a decrease in the number of erythrocytes (red blood cells), that is, to anemia and
cause the patient to become weak. Patients with multiple myeloma typically
suppression of the function of the immune system, which leads to 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 is suspected in a person with changes in blood tests
and urine, in the presence of bone pain and pathological fractures. Diagnosis
is confirmed if the patient has two of the four signs listed below.
. In the study of bone marrow obtained by puncture, among all cells
plasma cells make up at least 10%.
. X-ray images 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).
. Biopsy of bones or other tissues reveals accumulations of tumor
plasma cells.
Solitary plasmacytoma is diagnosed if:
. Tumor biopsy reveals a single focus of plasmacytoma.
. Other foci of reproduction of plasma cells, outside the found tumor,
cannot be found.
Patients with solitary plasmacytoma may also have an M-gradient in the blood or
in urine. The diagnosis can be considered definitively confirmed if, after removal
tumors (surgically or with the help of radiation therapy) the M-gradient disappears.
Solitary plasmacytoma is usually an early stage of multiple
myeloma. It is known that the majority of individuals 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
feel absolutely fine. 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 assess
main characteristics of the disease. Doctors in this situation are looking for answers to two
main question.
How big 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. The cell mass is
an indicator of how long the disease has developed in the patient's body. All in all,
the larger the cell mass, the more the normal biochemical
body balance and immune system function. The larger 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
myeloma.
How aggressive is the disease? Or more simply, how quickly
plasma cells multiply. An increase in the number of cells occurs
during a process called mitosis. The essence of mitosis is doubling
chromosomes of a cell (its genetic information) which then evenly
distributed over two new ones formed as a result of the division of the maternal
cells. In industrialized countries, the "aggressiveness" of multiple
myelomas are measured using a method called "tag index". Index
label 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
the number of plasma cells. Its evaluation is important because the multiple
myeloma with lower cell mass but high label index usually leaks
more aggressive than a disease with a larger cell mass (with more
severity of symptoms) but with a lower label index. high
aggressiveness of multiple myeloma is another argument in favor of
to start chemotherapy immediately. Such patients require more
careful observation, even if the multiple myeloma cell mass
(severity of symptoms) is not great. Unfortunately, in our country we do not have
the ability to measure the tag index. However, to assess the "aggressiveness"
multiple myeloma, you can use the concentration of albumin and so
called C-reactive protein in serum.
The answers to these two questions are also important because they allow us to estimate the probability
success with various treatments. For example, some therapies
work better with more aggressive myeloma. The evaluation of both parameters (cellular
weight and aggressiveness of the disease) is important for assessing the prospects for treatment of the patient.
If these indicators decrease during therapy, this indicates in favor of
that the treatment has a positive effect.
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 take some of them as an example.
. Plasma cell type based 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 the human
organism and capable of influencing the vital activity of various cells
(interleukin 6, interleukin 2, beta-2-microglobulin, C-reactive protein).
. Response to treatment, or in other words, whether they go away during treatment
symptoms of the disease and whether the values of laboratory parameters change,
characteristic of myeloma (concentration of the M-gradient in the blood).
In some cases, the evaluation of some indicators provides additional information
about the aggressiveness of multiple myeloma, others say nothing about the speed
reproduction of plasma cells, but based on clinical practice allow
make predictions for the future.
Thus, a patient with multiple myeloma, before choosing a treatment, should
undergo a large number of different studies to assess the nature
their disease, its aggressiveness, the study of prognostic factors, and the degree of violation
physiological functions of the body. Doctors do not prescribe tests from "idle
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 the further progression of the manifestations of the disease,
leading to violations of the main biochemical processes, to the weakening
functions of the immune system and life-threatening patient. In other words, on
against the background of treatment, the steady progression of the disease, characteristic of its
natural flow.
. Temporary "mitigation" of the disease - a decrease in painful symptoms that cause
feeling of discomfort and improvement of the basic functions of the body.
. Remission induction - a significant reduction in the manifestations of the main symptoms
diseases, temporary elimination of all visible signs of multiple myeloma.
. "Recovery" or achieving permanent remission (very rare).
In other words, the treatment is prescribed to improve the patient's well-being and
normalize the functions of his body. For a certain period of time, it may
reduce the severity of the symptoms of the disease or even stop the natural
the 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
treatment set themselves the task of completely curing patients, however, evidence
there is currently no such possibility.
4. What types of treatment can be used for multiple myeloma?
Chemotherapy, by killing malignant plasma cells, is performed with the aim of
achieve remission or even cure the patient. Its basis is
cytostatic anticancer drugs given by injection
or in the form of tablets.
The most commonly used combination for the treatment of multiple myeloma
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: MP is melphalan (Alkeran) and prednisone, VMBMCP -
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 younger than 65-70 years
capable of withstanding large doses of anticancer drugs. Duration
one course of chemotherapy is approximately one month. Chemotherapy can
carried out in a hospital or outpatient setting (i.e. chemotherapy drugs some patients
can be taken at home). Sometimes outpatient treatment is preferable,
because in the hospital there is a risk of infection with dangerous "in-hospital"
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 reception 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 decrease
plasma cells in the bone marrow and an abnormal monoclonal protein in
blood and urine of the patient, one can judge the effect of chemotherapy. Necessary
emphasize that the treatment is considered effective even in cases where there is not complete
remission has not been achieved.
Radiation therapy is usually performed locally on the foci of bone tissue destruction,
causing pain and/or risking dangerous fractures. Radiation
can be used for the final "cleansing" of plasma cells after
surgical removal of plasmacytoma. The affected area is affected
a certain, controlled dose of radiation. Radiation therapy kills plasma cells
cells faster than chemotherapy and comes with fewer side effects
effects. Therefore, it is usually used to quickly eliminate pain and to
impact on large foci of destruction in the bone tissue, as well as in patients not
able to tolerate chemotherapy. It is also possible to combine radiation and
chemotherapy. Irradiation is usually carried out five days a week for several
weeks or months. During the course of radiation therapy, the patient may be
Houses. The chemotherapy plan includes the dose of radiation, the area to be treated, and
duration of treatment.
Interferon-. usually used to maintain the effect of the
chemotherapy or bone marrow transplant. It helps prolong the condition
remissions. It is believed that it is able to limit the reproduction of plasma cells.
As a result, interferon-. capable of delaying (but not preventing)
relapse of the disease. Interferon-. usually in an outpatient setting
conditions 3 times a week in the form of subcutaneous or intramuscular injections.
Bone marrow or peripheral blood stem cell transplantation
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 so far
there is no direct evidence for this. Transplantation is based on high-dose
chemotherapy is sometimes combined with total body irradiation. This impact
so strong that it can completely destroy the hematopoietic tissue, without which
human life is impossible. Stem cells transplanted to the patient replace
dead, protecting the patient from fatal complications. So the value
transplantation in that it allows such a powerful therapy, the implementation of which in
under normal circumstances it would be too risky. There is hope that with
all diseased cells will be destroyed by the bone marrow. bone marrow for
transplantation is taken or from a donor selected according to special criteria
(allogeneic transplantation), or from the patient himself (autologous transplantation).
When the bone marrow of the patient himself is used for transplantation, before the introduction
they are often cleared of tumor cells with the help of special preparations or
antibodies. Before bone marrow or peripheral stem cell transplant
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 vital
the patient's activity should be limited. transplantation is the most
aggressive, of the currently existing treatments 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 who are trying with its help to discover new
opportunities to increase the life expectancy of patients with multiple
myeloma, and clarifying its place in the arsenal of drugs for the treatment of this severe
diseases.
Stem cell harvesting is a procedure for 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
the protein in their blood reaches an alarmingly high level and needs to be reduced quickly.
The procedure consists in taking 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 infections. 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
to reduce the severity of anemia and associated symptoms (for example,
weakness). Surgical methods may be used to remove tumors,
restoring bones after fractures or reducing the severity of pain.
Other appointments. It is desirable that, without the permission of the attending physician, the patient
multiple myeloma did not take any medication. So uncontrollable reception
non-narcotic analgesics (brufen, diclofenac sodium or voltaren, indomethacin
etc.) in patients with impaired renal function, may lead to deepening of the renal
insufficiency.
5. How to choose the right therapy for you?
The question of the choice of 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 are well aware of this, 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
have enough time to spare. In addition, it must be remembered that
some momentary decisions need to be made taking into account plans for the future.
For example, if autotransplantation of stem cells is planned, the use of
some drugs (eg Alkeran) is highly undesirable.
This does not mean that patients themselves determine their treatment. However, it is important
ask your doctor what action to take immediately, and
which one can wait. When the situation allows, before starting therapy, think about
advantages and disadvantages of various treatment programs.
To begin with, understand for yourself 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
aimed at eliminating the most dangerous symptoms. The implementation of others can
be postponed, and you will have enough time to think.
It must be remembered that there is no absolute, suitable for all
treatment for multiple myeloma. Even a bone marrow transplant or
peripheral blood stem cells is not necessarily indicated for young and well
feeling sick, although this procedure is relatively “easy” to perform in
this category of patients. Some patients in the early stages of the development of the disease
need only the supervision of a hematologist. Carrying out standard
chemotherapy programs that aim to achieve remission cannot
guarantee you the expected result. Physicians know the likelihood of success with
use of various methods of treatment and can apply special
diagnostic tests to select the programs that are best for you
way. Everything said about standard chemotherapy applies equally to
transplantation, the purpose of which is recovery.
The time frame within which decisions must be made concerning the main
aspects of the treatment of multiple myeloma, we present in the following table.
TREATMENT EFFECT OBJECTIVE EXAMPLES DECISION-MAKING TIME

STABILIZATION Counteraction to life-threatening violations of the biochemical
homeostasis and immune system caused by myeloma
*
Plasmapheresis to reduce blood viscosity
*
Hemodialysis when kidney function is severely impaired
*
Treatment for hypercalcemia (Aredia), may include chemotherapy
.... ... ...
TEMPORARY "REDITION" OF DISEASE Reduced discomfort, increased ability
perform normal functions
*
Radiation to stop bone destruction
*
Erythropoietin to reduce the manifestations of anemia
*
Orthopedic surgery 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 radiation area
...... ...
RECOVERY Permanent remission (currently
practically unattainable)

Bone marrow transplantation, making it possible to tolerate very high doses of chemotherapy
......
What should you talk about with your doctor?
Below is a list of questions we recommend you ask first.
. Ask for a general treatment plan.
. What tasks are planned to be solved in the course of therapy?
. How long will it take for treatment?
. How often do you need to visit a medical facility? Is it necessary to be treated
hospital?
. What complications may accompany the treatment. How does the disease and its treatment affect
on the ability of the patient to perform their basic functions (for example, to work,
serve yourself, etc.). How do people feel before treatment, during treatment
and after graduation? What do other people with multiple myeloma look like?
What is the total duration of the course of therapy. What is the length of the period
recovery after treatment?
. What does a multiple myeloma follow-up program include?
. How much does it cost? And to what extent the costs can be reimbursed
insurance system?
Find out how the treatment you proposed worked for other patients in similar
situations. The effectiveness of treatment can be assessed by various parameters.
Try to get answers to the following questions.
. What is your experience with the proposed treatment? How many patients
received such therapy? How long did the doctors observe them?
. What is the probability (chance) of achieving a complete or partial remission? Which
factors accompany the best, and which are the worst forecast?
. What actions can be taken in case of a recurrence of the disease?
. What can be done to reduce bone pain, treat pathological
fractures, anemia, general weakness, hypercalcemia? What are the signs of
good or bad prognosis in these situations?
. What is the life expectancy of patients receiving your planned
treatment?
Complications of therapy. Used to treat multiple myeloma
potent drugs, the action of which is aimed at
destruction of tumor cells and / or 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 "sick" but also
"healthy" cells of the patient. Therefore, patients receiving them should be under
special care to avoid or minimize its side effects.
Complications of chemotherapy depend on the type of drug, its dose and duration.
reception. The most affected by the action of anticancer drugs are
rapidly dividing cells. Among the normal cells of the human body, they 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, the patient may develop hair loss, stomatitis (lesion
oral mucosa), decrease resistance to infections (in
a 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
a 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 effects of chemotherapy drugs on special centers in the brain. This effect
temporary, and it can be eliminated with the help of special medicines.
drugs such as Novaban.
In addition, some anticancer drugs can
adverse effects on certain internal organs, such as the heart
(adriamycin) and kidneys (cyclophosphamide). Thus, doctors each 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 are observed in patients as a result of treatment? When they
develop? How often do they occur (in what percentage of patients)?
. How dangerous are the side effects of the therapy? Do they represent
a threat to life? Will they be accompanied by pain? What is 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 methods. In almost every case, different
treatment approaches. For this reason, you are advised to get answers to
next questions.
. What alternative treatments can be applied?
. What are their positive and negative sides?
. What is more profitable in my case, the immediate start of treatment or observation without
chemotherapy?
Remember, making a decision takes time.
In order to make a choice, you will need information about your new
disease. Much 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, understand the medical literature,
devoted 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 give advice and explanations to you and your loved ones throughout
period of treatment. Some patients are very curious and want to
discuss all issues related to their disease, its treatment and prognosis. Other
depressed, and only interested in what awaits them tomorrow.
Most physicians feel this and change their approach depending on
the wishes of the patient. You can speed up and simplify this process if you clearly express your
a desire as to how deep you want to go into problems,
concerning the treatment of multiple myeloma, and participate in decision-making.
Remember, the choice of treatment is very important for the quality and duration of life.
patient with multiple myeloma. Remember, before making a final decision,
it is good to know the opinions of various specialists, this will not spoil the relationship with your
doctor.
Since multiple myeloma is a rare disease, the number of specialists
knowledgeable about this problem and the number of medical centers that treat this
pathology is quite small. Doctors know this and will advise you on the right specialists.
A situation is quite acceptable when a patient, 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, a careful study of all
sides of the issue, serious reflection and courage. However, it seems important that
the patient and his relatives during the entire period of the disease had enough
information about the course of treatment, and understood its goals and possibilities.