Myeloma
Myeloma is an oncological disease of the blood that is characterized by the damage of B-lymphocytes and the development of oncologically altered plasma cells from them, which synthesize antibodies. Myeloma is also characterized by various manifestations in the human body. There are multiple myeloma or diffuse myeloma, which is characterized by the development of multiple lesions in the body. There is also myeloma of blood, which is characterized by a decrease in blood viscosity and a violation of the formation of blood cells. And there is, for example, bone myeloma, which is characterized by an exceptional lesion of bone structures.
Actually, the disease got its name because malignant myeloma cells infiltrate the bone marrow in various tubular bones and cause multiple lesions (diffuse myeloma or bone marrow myeloma). By the way, the very name of the disease "myeloma" comes from the Greek, where "myelos" means "bone marrow", and the end of "om" - is common to the names of all tumors. Myeloma is translated literally, as a "bone marrow tumor."
Myeloma of cause
Specific causes that would lead to the development of the disease there.
It is believed that the etiological factors of the occurrence of myeloma may be the effects of ionizing (radiation) radiation, oil products, asbestos, benzene. A dangerous precondition for myeloma to appear in the human body is age - the average age category for this disease is 65 years. It is established that most often myeloma affects men.
And because of what there are malignant prototypes of myeloma? First, we need to understand the mechanism of the formation of B-lymphocytes, the progenitors of plasma cells.
Before the transformation into a plasmatic cell, the B-lymphocyte passes through the following stages.
In the bone marrow polypotent (the source of development of all subsequent types of cells), the stem cell turns into a precursor of B-lymphocyte (pre-B-lymphocyte). Then the pre-B lymphocyte under the influence of various stimulant proteins is transformed sequentially first into the B-lymphoblast (immature B lymphocyte), then the lymphoblast is transformed into the B-lymphocyte itself.
Then the plasma cell forms: The lymphocyte reaches the lymph node and settles into the tissue of its follicle, forming "germinal centers" - secondary follicles of reproduction, where plasma-plasmoblastic cells migrate to the brain substance of the lymph node, finally passing proliferation and maturing into the plasmocytes. Synthesis of plasma cells is triggered when foreign information enters the body, namely, foreign antigens. Then the macrophage "presents" this information to the B-lymphocyte and activates it on the synthesis of plasma cells. Also, remember that all the daughter cells will remember all the information that their B-lymphocyte parent had.
Fully formed and healthy plasma cells have one feature that other cells do not have: they are able to produce antibodies to various dangerous substances for the body (a kind of "aliens" or antigens). These antibodies are called immunoglobulins, and there are 5 types.
Thus, B-lymphocytes with the help of macrophages, remember which alien agent attacked the body. Then he gives birth to his daughter plasma cells and gives his "memory of the stranger" to them and determines which of the five types of immunoglobulins need to be synthesized to plasma cells in order to defeat and remove the foreign antigen from the body.
With myeloma, B-lymphocytes can still produce new plasma cells that can synthesize immunoglobulins. But there is a problem: immunoglobulins in such cells are monotonous in structure. This is explained by the principle of tumor cells of myeloma: all cells of the tumor are born by one progenitor cell and carry the same information. We can say that the place of normal B-lymphocytes is occupied by abnormal cells, which begin to synthesize identical plasma cells with the same type of information. This kind of "clone attack": these plasma cells can not attack infectious and foreign agents, because they did not receive from their progenitor cells any information about strangers, that is, roughly speaking, the cells turn out to be "stupid". They gather in the red bone marrow and form the very substrate of myeloma. And such myeloma foci can appear in many bones, where this type of bone marrow is present. Usually, myeloma likes to hit tubular bones.
And, as a result, the body appears:
1. Clones of plasma cells that release the same type of immunoglobulins. They are called monoclonal (verbatim: "from one clone") paraproteins. The vulnerability of the organism to infections is developing.
2. There is an accumulation of these same immunoglobulins in the bloodstream, in the urine and their negative impact on individual organs. The kidneys are most often affected, the viscosity of the blood increases.
3. Pathological myeloma cells produce an osteoclastic factor that triggers the destruction of bone structures in the body and the consequences of high blood levels, due to the destruction of bones and calcium.
4. Clone cells are collected in the bone marrow and a myeloma substrate appears. The appearance of myeloma foci in various tubular bones of the body.
In the pathogenesis, characterized by myeloma, two stages of the flow are distinguished.
The first is chronic. In her myeloma cells have a low ability to develop. There is no depression of the formation of other bone marrow cells (myeloma depression).
The second stage is acute or terminal. Tumor cells of myeloma mutate, producing their clones with increased reproduction. As a consequence, all sprouts of formation of the elemental elements can be suppressed, and myeloma metastasizes throughout the body. In addition, myeloma can degenerate into other oncological species (eg, lymphosarcoma ).
Stage myeloma
The course of myeloma is divided into the following stages (they are similar to those stages of pathogenesis):
1. Asymptomatic period: There are no changes in the status of patients, there are no clinical signs of the disease yet, but protein (proteinuria) can be determined in urinalysis (usually at random, for example, preventive examination).
2. Midsummer Period: Here all the characteristic clinical symptoms that trigger myeloma will be expressed.
3. Terminal stage: metastasis of myeloma to other organs is observed. Oppression of other structures of the bone marrow, attachment of secondary infections, cachexia of the body.
Also myeloma is divided into stages according to the severity of the process and clinical manifestations: the level of calcium in the blood, the concentration of hemoglobin (this is how the activity of bone marrow myeloma is checked), radiologic signs of bone destruction.
Stage I
The level of hemoglobin exceeds 100.
The calcium values are normal.
X-ray: there is no destruction of bones or there is a single focus.
Low level of paraproteins.
II stage
The level of hemoglobin is from 85 to 100. The values of calcium are rising.
X-ray: there is disintegration and destruction of bone (osteolysis and osteodestruction).
III stage
The level of hemoglobin is low - less than 85 grams in 1 liter.
Extremely high levels of calcium.
X-ray revealed multiple processes of osteodestruction.
Also, two substages are created for each stage: A and B. They are divided according to the presence or absence of renal dysfunction, namely: the level of serum creatinine. So, stage A is characterized by a normal serum level of blood, and stage B - its elevated level.
Myeloma symptoms
Clinical manifestations of myeloma are caused by the following factors: bone marrow and bone infiltration by tumor plasma cells (myeloma of bones), secretion of monoclonal paraproteins and the spread of a tumor outside the bone marrow.
In the clinical course that accompanies myeloma, it is customary to distinguish the following syndromes (symptom complexes):
1. syndrome of bone damage;
2. defeat of the hematopoietic system (blood myeloma);
3. kidney damage;
4. a syndrome of visceral pathology;
5. Syndrome of secondary immunodeficiency (secondary infection);
6. hyperviscosity syndrome;
7. neurological syndrome;
8. hypercalcemic syndrome (consequences of massive destruction of bones).
Syndrome of bone pathologies
One of the most important manifestations of myeloma is bone damage syndrome (myeloma of bones). Its manifestations are explained by the defeat of bones by tumor clones, increased activity of osteoclasts, and the production by clone cells of factors that stimulate osteoclasts.
There are pains, most often plasmocytes suffer from the bones of the chest. At first the pains are not permanent, quickly fade. But with an increase in the activity of the disease, the pain becomes unbearable, they are triggered by physical activity or body torsions. By the way, by tapping with the tip of the index finger on the bones it is easy to determine their soreness. In addition to the thorax, vertebrae and tubular bones (limb bones) are affected. Therefore, complaints about localization of pain in these areas are also possible.
Damage to the bones is most often affected by the flat and short bones of the skeleton (skull, pelvis, sternum, vertebrae). Therefore myeloma in the bones will be manifested by the following radiological picture: "fish skeleton" or spine as "bamboo stick" - flattened bodies of vertebrae. This will lead to a decrease, "subsidence" of the patient's growth, and the bones on the X-ray will be as if "moth-eaten", "knocked out punch". These are signs of massive osteoporosis and osteodestruction. By the way, with diffuse forms of the disease (diffuse myeloma), only osteoporosis will be observed.
Since the normal structure of the bones is disrupted, very often the patients get different fractures: there is no need to make significant efforts to do this, it is enough to get just a small bruise.
Damage to the hematopoiesis system
Myeloma of the blood develops more at the terminal stages, when the tumor plasma cells with their growth inhibit other germs of hematopoiesis.
This syndrome is characterized by the appearance of anemia: you can notice the characteristic "anemic" pallor of the skin. If the process progresses over a period of time, neutropenia and thrombocytopenia will develop in the blood. There will be a syndrome of "pancytopenia", in which the tumor will displace all the hematopoietic germ from the bone marrow.
Renal lesions
The kidneys are affected by the deposition of paraprotoins in the kidneys. Bens-Jones proteinuria appears (detection of myeloma Bence-Jones protein in urine). This all leads to the development of myeloma kidney and amyloidosis. In addition, some types of myeloma paraproteins are toxic and, deposited in the kidneys, can easily cause kidney failure.
Syndrome of visceral pathologies
This syndrome occurs when the breakthrough of myeloma in the body. They easily damage various visceral (internal) organs. The most "tasty" organ for myeloma is the liver, and behind it is the spleen. It is easy to verify with the help of palpation: both the liver and spleen will differ in larger sizes than their normal size.
In more rare cases, myeloma can enter the lungs. Then myeloma will result from the development of hemorrhagic effusion in the lungs. It is also possible secondary damage to myeloma of the skin, as a result of dissemination of oncocells over the body.
Syndrome of secondary immunodeficiency
Since normal immunoglobulins, which protect the body from foreign antigens, due to the effects of myeloma, are absent, the body becomes vulnerable to various infections. Often, they are the cause of death in patients with myeloma: the body simply has nothing to protect itself from infections. Due to the pathological effects of myeloma, bacterial complications appear. More severe cystitis and pyelonephritis . Also, the syndrome of pancytopenia can progress. The functioning of neutrophils is reduced, which means that their function of protecting the body from infections is also violated.
Syndrome of high viscosity of blood
At the heart of the increase in blood viscosity is the high concentration of myeloma protein in the bloodstream. As a result, its microcirculation is disturbed and blood hardly reaches, or does not reach the individual parts of the body at all. This explains the following symptoms: a feeling of "creeping crawl" in the body, various visual impairments, dizziness . These symptoms can lead to the development of acrogengrams.
In addition, myeloma paraproteins "envelop" the platelets and prevent them from performing the aggregation function. As a consequence, there is a syndrome of increased bleeding: the skin appears hemorrhages, may bleed mucous membranes or begin nasal bleeding.
Syndrome of neurological disorders
Since plasmocytes can affect both the dura mater and the integrity of the bones of the skull, hitting the vertebrae, squeezing the roots, there will be such phenomena as paresthesia: "creepy" in the body, numbness, the function of the arm or leg may be impaired, muscle weakness may appear, can reduce sensitivity to pain.
Syndrome of hypercalcemia
Since the body is observed massive destruction of bone tissue myeloma, there is calcium release from the tissue and its accumulation in the blood. Excessive excess of normal levels of calcium leads to the appearance of vomiting, nausea. Also, consciousness can be disturbed and drowsiness may appear. Calcium crystals are deposited in the interstitium of the kidneys and cause nephrocalcinosis and renal failure.
Diagnostic criteria of myeloma
The main here are two criteria: the presence of more than 10 percent of the plasmocytes in the puncture of the bone marrow, its plasma infiltration and detection of monoclonal immunoglobulin during electrophoresis. The diagnosis of myeloma can be established only when two of these criteria are combined.
Myeloma treatment
Without a doubt, the main place in the treatment of manifestations that myeloma has on the body is given to chemotherapy, with hematologists developed 2 schemes for the treatment of myeloma:
1. The scheme MR. It uses a combination of the following drugs: Melphalan / Alkeran + Prednisolone. Melphalan and Prednisolone are taken from 1 to 4 days of chemotherapy, and the dose of Prednisolone from the 5th day of therapy is reduced and canceled on the 9th day. Then break for up to 6 weeks and the circuit is repeated. This scheme is the "gold standard" of myeloma treatment.
2. The scheme M2. It uses Vincristine + Cyclophosphane + Alkeran + Prednisolone. This scheme is suitable for the treatment of patients older than 65 years, or for the treatment of aggressive forms of myeloma.
Also, at present, bisphosphonates give good results in the treatment of myeloma. Particularly well, these drugs treat damage that has on the body bone myeloma. The drugs can suppress the activity of osteoclasts, stop the destruction of bone and reduce the spread of the myeloma itself. Representatives of this series of drugs are Bonefos, Bondronate, Aredia.
Treatment of concomitant manifestations of myeloma
Much attention is paid to correcting those physiological processes of the body that were directly affected by myeloma (for example bone damage) and indirectly (hyperkaliemia syndrome, which occurs as a consequence of the effect of myeloma on bone structures).
Treatment of myeloma hypercalcemia
Hypercalcemia is treated according to the degree of its severity. At an easy degree it is better to treat to apply hydration of an organism: up to 3л mineral water in day. At high degrees of calcium, intravenous infusions are prescribed, and they are combined with intravenous administration of Furosemide. This procedure should be carried out by monitoring potassium levels.
Treatment of neurological disorders caused by myeloma
If myeloma led to compression of the spinal cord, then radiotherapy is used. To this addition, the use of Dexamethasone is prescribed. It is also possible to treat compression of the spinal cord by administering intensive doses of chemotherapy. Operative intervention is practically not used.
Treatment of impaired myeloma of kidney function
An important point of appointment of therapy in myeloma is the correction of the condition in renal failure and its prevention. They are engaged in correction of hypercalcemia in the patient, from the first courses of chemotherapy prescribe the administration of Allopurinol. Carry out timely treatment of any urinary infections and do not use those substances that are characterized by increased nephrotoxicity. At the slightest signs of renal dysfunction prescribe a preliminary hydration.
Correction of hyperviscosity syndrome
For the treatment of the syndrome with increased viscosity of the blood, the use of plasmapheresis is used. In patients with myeloma, using a special apparatus through which blood is run, plasma is removed, which contains a large number of monoclonal paraproteins synthesized by myeloma and is replaced by a donor one. Contraindication is the presence of a paraproteinemic coma in a patient: a condition in which the percentage of myeloma paraproteins in the blood is so high that with a plasmapheresis it will cause disturbances in the body that are incompatible with life.
Anemic syndrome affects most patients with myeloma. This is due to the fact that the myeloma gradually grows in the bone marrow and can "press down (oppress) the foci of formation of the formed elements of the blood.
If the chemotherapy is carried out correctly and on time, then this syndrome, as a rule, disappears. But it is important to know that the improvement will come only after several courses of chemotherapy treatment (during this time myeloma will lose the ability to depress the bone marrow) and then when the kidney function improves (and this is because myeloma kidneys filled with paraproteins of myeloma can not secrete the necessary for the creation erythropoietin).
Therefore, in case of severe degrees of anemia and myeloma, transfusions of the donor erythrocyte mass are recommended. In addition, it is important to maintain a hemoglobin level above 10 grams per 1 liter, and better and above 70 grams.
A good effect in the treatment of myeloma anemia is achieved with the appointment of erythropoietin 3 times a day. But this requires a low level of erythropoietin in the body itself and an adequate compensation of iron losses, which will be intensively spent with artificial stimulation of erythropoiesis. This use of erythropoietin can help avoid complications with blood transfusions and erythrocyte mass.
If the patient has a deep inhibition of granulocyte cells of the lymphoid germ and a similar damage to the platelet sprout (myeloma pancytopenia syndrome), then in the treatment of myeloma, do not recommend reducing the dose of chemotherapy drugs. A good effect will be the holding before chemotherapy of myeloma in such patients treatment aimed at stimulating the formation of oppressed cells and the addition of blood substitution therapy.
The syndrome of secondary infection is treated according to the protocol of treatment of patients with immunodeficiencies. But first they take to research, to account for and prescribe medications and their specific doses, urine and sputum, carry out a bacteriological study of the blood. With a sudden increase in temperature immediately begin antibacterial therapy (also excluding nephrotoxic drugs). Incidentally, isotonic solutions are administered and an abundant drink is prescribed. This is done to prevent the development of acute renal failure in patients, since the normal function of myeloma kidneys is greatly reduced, and they become more vulnerable to infections of all kinds.
In order to determine whether there is an effect of chemotherapy or not, you need to know certain criteria for the effectiveness of treatment:
1. There should be no paraprotein in the bloodstream. Also, it should not be in the urine.
2. When puncturing tubular bones, the preparation should contain less than five percent of the plasmocytes.
