Myeloma is a disease of a lymphoproliferative nature, the morphological substrate of which is the plasma cells that produce monoclonal immunoglobulin. Myeloma or multiple disease is considered a tumor disease of the lymphatic system with a low degree of malignancy. For the first time in our country, this disease was described in 1949 by GA Alekseev.
Myeloma is about 1% among all malignant oncopathologies, and among hemoblastoses - 10%. And people of the black race are sick much more often than others, although the disease is found among all races. Myeloma mainly affects people after forty years.
Today, this disease is often referred to as a plasmacytoma or multiple myeloma. This concept includes the disseminated tumor process of the B-lymphocyte system, which consists of degenerated plasma cells. Myeloma is based on the development of the most important symptoms, such as laboratory and clinical, as well as complications, such as myeloma cell infiltrations in the bone marrow and the formation of a significant amount of paraprotein by cancer cells that are defective immunoglobulins. In addition, there is a decrease in the synthesis of conventional immunoglobulins.
Myeloma disease causes
At the moment, the etiology of myeloma is not yet clear. However, it is proved that myeloma, develops as a consequence of ionizing radiation, which is considered an alleged factor in the etiologic involvement in the onset of this disease. Ig belong to the majority of globulins, which are produced by malignant plasmocytes after antigen stimulation. Any such cell can synthesize a single epitope with a lambda or kappa light chain.
An uncontrolled process of synthesis of monoclonal M-proteins leads to tumor transformations of individual precursor cells. It is believed that myeloma produces these cells, which can be polyponent stem cells. This disease is characterized by multiple chromosomal abnormalities, such as thiosomes of the thirteenth chromosome, trisomy of the third, fifth, seventh, ninth, eleventh, fifteenth and nineteenth chromosomes. Very often, there are violations in the structure of the first chromosome, which does not have a specific defect.
From the tumor changes of progenitor cells to clinical symptoms, a characteristic stage takes place, which lasts twenty, and sometimes thirty years. A plasmatic cell that has undergone malignancy can penetrate into the kidneys and bone tissue and form the symptoms of myeloma as a widespread multifocal tumor process. In some cases, malignant cells divide and multiply locally, which gives rise to the development of solitary plasmocytes. These tumors are formed as a result of secretion of M-protein, which subsequently becomes the reason for the appearance of an obvious clinical picture of myeloma.
The etiological factor in the formation of myeloma is associated with the proliferation of the pathological nature of plasma cells. This process occurs mainly in the bone marrow and sometimes in outbreaks of extramedullary lesions. Animal studies confirm that media and genetic factors are involved in the development of tumor plasma cells. But the role of these factors in humans has not yet been proven. There is also information about cases of family myeloma, but there is no exact evidence of its predisposition at the genetic level for a person.
Thus, in the etiology of myeloma, the role of two factors is assumed. As a rule, it is ionizing radiation and mutations in progenitor cells.
Myeloma illness symptoms
For clinicians, myeloma with its numerous manifestations poses rather complex problems. The symptomatology of the disease is conventionally divided into manifestations, which, as a rule, are related to the local localization of the tumor, as well as to the effects of malignant cell products. They are metabolites and immunoglobulins of monoclonal properties.
In 70%, the first symptom of myeloma was bone pain, which is characterized by a local and acute onset caused by a minor trauma, but without fractures. As a rule, pain migrates through the body, it can sometimes disturb a patient at night and arise after a change in body position. Very often, pain can appear in the chest area, however, lesions can affect the pelvic and tubular long bones.
The formation of pain in the joints speaks of amyloidosis. For a certain stage of the disease is characterized by the mandatory occurrence of anemia , as a result of which there is a characteristic weakness and rapidly arising fatigue.
Myeloma is very rarely characterized by symptoms such as weight loss and fever. However, these symptoms appear at a much greater degree of severity, and also after infection. In 7% of patients bleeding occurs as complications of myeloma. In the debut of the disease, hypercalcemia is revealed, which is caused by vomiting, constipation, thirst, polyuria with confusion and sometimes even coma. Myeloma can begin with kidney failure, which very quickly becomes oliguria and requires immediate hemodialysis.
Changes in the physical nature can be minimal at the very beginning of the disease. Patients are noted pallor from the skin and insufficient heart function, as a result of a small amount of bone marrow. In areas of ostiolysis during palpation, the bumpy and painful bone surface is determined. After squeezing the spinal cord or nerve endings due to fractures or fractures of the spine, as well as various deposits outside the bones, sciatica , paraplegia appear, motor skills are disrupted and control over the sphincters is lost. Very rarely, hepatosplenomegaly occurs with a moderate increase in the liver in 26%.
Quite often, bone lesions are detected by the time the clinical picture develops. Based on radiography in 80% myeloma affects the bone tissue. Deformation of bones leads to generalized osteoporosis, osteolysis with single or multiple foci, to peculiar fractures, as well as damage that can also be captured by nearby soft tissues. The most minor injuries cause various fractures. Also very often the lesions are exposed to the pelvis and skull bones, vertebrae and ribs. In case of defeat with myeloma of the lower jaw, there is a fracture in the process of eating.
One of the dangerous complications of the disease is a violation of the kidneys. This dysfunction is detected in half of the patients at the time of diagnosis of myeloma and is the underlying cause in the fatal outcome of patients. The function of the kidneys is one of the most important single factor that determines the prediction of myeloma. These disorders of kidney function can be based on various mechanisms that lead to the development of renal failure in acute form or chronic, nephrotic syndrome or cause Fanconi syndrome. And, in addition, there are symptoms in the form of hyperuricemia, hypercalcemia and increased blood viscosity. Serum increases the level of calcium, and polyuria and vomiting, lead to loss of water.
Myeloma is characterized by lesions of the nervous system as a result of the penetration of the pathological process into the nerve processes or the spinal cord, and also as a consequence of hypercalcemia or blood viscosity. Sometimes it is possible to observe the symptoms of polyneuropathy as a result of amyloidosis. Practically in 30% there is a compression condition of a spinal cord and defeat of a horse tail. Radiculopathy develops after the spread of the pathological process from the vertebrae to extradural space. Very often there are characteristic pains in the back, which precede paraplegalia. As a result of compression, there is weakness in the muscles, sensitivity is lost, urination is disturbed, which lead to paresis.
The most common myeloma is located in the thorax, which can be established with the help of an X-ray and tomographic examination.
Neuropathy of peripheral localization is very rare. And if amyloidosis joins it, carpal tunnel syndrome develops. You can also find neuropathy of the peripheral sensorimotor property in the form of a stocking glove. It can also be manifested in the absence of deposits of amyloid type; arise against a background of a solitary lesion or multiple foci of myeloma. There is a definite relationship between neuropathy and osteosclerotic changes, as well as polycythemia, skin pigmentation and thickening of the phalanges of the fingers. At these times, the protein in the cerebrospinal fluid rises. Due to the defeat of myeloma, the bones of the skull develop paralysis of the nerves of the cranial-cerebral divisions, and when the orbital bones are damaged, the functions of the oculomotor and optic nerves are violated, followed by ophthalmoplegia.
In 10% of patients with myeloma, macroglobulinemia syndrome is observed. It is the syndrome of increased viscosity that causes bleeding from the nose and gums. Also, patients very often lose sight, and the most constant symptom of the disease is retinopathy. It is characterized by hemorrhages of a flaming nature, veins that are enlarged and tortured, retinal vein thrombosis, optic nerve puffiness. Neurological symptoms are very rich. It can begin in the form of drowsiness, headaches or dizziness, and then go into conditions such as loss of consciousness and coma.
In 20% there is hypercalcemia, which occurs with bone resorption by osteoclasts. This is manifested by a lack of appetite, stomach disorders in the form of nausea, vomiting and constipation . Much later, there is a drowsy state with confused consciousness, turning into a coma. Polydipsia and polyuria develop, and then calcium is deposited in the kidneys, dehydration of the body occurs, which causes kidney failure.
In 15% of the melomy disease there is a complication in the form of bleeding.
Very often myeloma reduces the ability to resist infections. Practically at half of patients at different stages of disease the serious form of an infectious complication develops, which becomes the reason of frequent cases of a lethal outcome. The most common infections are the urinary tract and respiratory system, the causative agents of which include H. influenzae, pneumococcus, meningococcus, intestinal bacteria, as well as the herpes virus.
Myeloma disease of stage
Currently, the S. S. Salmon and B.Durie staging system is generally recognized, which is based on the dependence of the weight of malignant cells on laboratory and clinical performance, as well as the prognosis of myeloma.
At present, there is another system, based on the definition of parameters such as β2-microglobulin and albumin in the serum. The first, in this case, is a low-molecular protein, which is produced with the help of nuclear cells and excreted in the urine. Serum albumin is characterized by an indirect IL-6 content of osteoclasta- tivating and growth factor. The same system of stages in myeloma is suggested by IMWG, which is an international group in the study of this disease.
When using the classification of myeloma immunochemical properties, five forms of the disease are distinguished: Bence-Jones, A, E, G and D. Among the rare forms, one can distinguish non-secretive and M-myeloma. G-myeloma is found in 50%, A-myeloma in 25%, D-myeloma in 1%, the rest are insignificant and quite rare.
The stage of myeloma depends on the mass of the tumor. Therefore, for this pathological disease is characterized by three stages of the disease. The weight of tumor cells to 0.7 mg / m 2 (low) is characteristic of the first stage of myeloma, from 0.7 to 1.3 mg / m 2 (medium) - the second stage, more than 1.3 mg / m 2 (high) - The third stage.
Myeloma disease diagnosis
Three main criteria are used for the diagnosis. As a rule, firstly, it is necessary to identify clonal plasma cells, using myelogram, and a plasma-cell tumor when biopsied from a lesion. Second, determine the monoclonal Ig in serum and urine. Third, to detect signs of damage to tissues and organs that are associated with myeloma: hypercalcemia, renal failure, anemia, osteoporosis, or lysis in the bones.
When diagnosing myeloma, a special role belongs to the existing plasma-cell tumor lesion. This allows to identify patients with the disease in an active or symptomatic form.
For the diagnosis of myeloma, X-ray examination of the bones of the skull, collarbone, sternum, scapula, ribs, all parts of the spine, pelvic bones, femoral and humerus bones, as well as other parts of the skeleton according to clinical indications. Biochemical blood test allows to determine the total protein, albumin, calcium, creatinine, uric acid, alkaline phosphatase, LDH, transaminase and bilirubin. In the general analysis of blood, the leukocyte formula and the number of platelets are counted. Radial immunodiffusion allows to determine the level of immunoglobulins in the blood. Electrophoresis is used to detect densitometry.
Urine is also collected for general analysis and according to Zimnitsky, to determine the loss of protein in daily urine. And also reveal the level of paraprotein by immunofixation of proteins and electrophoresis.
Still use additional diagnostic methods such as MRI of the entire spine, cytogenetic studies, immunophenotyping of cancer cells.
Myeloma illness treatment
In the first stage (A) with a slow-moving form of myeloma, treatment does not require immediate therapy. Only with the appearance of increased paraprotein, hemorrhagic and hyperviscosity syndromes, with the progression of osteolytic lesions such as bone pain, compression of the spinal cord and spine, pathological fractures, hypercalcemia, renal dysfunction, amyloidosis, anemic syndrome and complications in the form of infections, begin specific treatment.
When the brain is compressed in the spinal canal, laminectomy and kyphoplasty are performed in complex treatment with Dexamethasone, local irradiation, and orthopedic fixations are used for pathological bone fractures.
The method of radiation therapy for myeloma is considered a palliative treatment of locally located lesions, especially if the pain syndrome is expressed. Dosage of irradiation is from 20 to 24 Gy for two weeks for five to seven sessions. For solitary therapy with plasmacytum, a total dosage of 35 to 50 Gy is prescribed. Basically, radiation exposure is used to treat injured skull bones in the face and base area.
The main method for treating patients diagnosed with myeloma is polychemotherapy with cyclose-specific drugs, especially alkylating agents such as cyclophosphamide, and melphalan, supported by corticosteroids. It is also important to consider that all alkylating drugs can cause the occurrence, in the future, of myelodyspatic syndrome or acute myeloleukemia. In addition, accumulated toxic effects on the bone marrow, which disrupt the production of stem cells, can interfere with autologous transplantation.
Most often, chemotherapy regimens are used to treat patients, such as M2 protocol, alternating - VMCP / VBAP and AB / CM. Nevertheless, the traditional treatment of myeloma with Alkoker and Prednisolone, as well as with polychemotherapy, does not exceed five percent in achieving absolute remission and the disappearance of paraprotein in urine and blood.
In the treatment of the primary resistant form of myeloma and relapses of a refractory nature, as well as with renal failure or for the rapid achievement of the effect in treatment, the use of Vincristine, Dexamethasone, and Doxorubicin over a four-day period was widely used for four days. The same scheme is used for three to four courses as a preliminary cytoreductive therapy before the appointment of high-dose chemotherapy (Melphalan at 150-200 mg / m 2). And then the stem cells are transplanted.
Very effective to date, pulse monotherapy with the use of corticosteroids in high doses, for example, Dexamethasone. This is especially effective for hemocytopenia, bone marrow depletion and the phenomena of renal insufficiency.
For the treatment of myeloma of an infected type, polychemotherapeutic regimens with Cisplastin are used: DT-PACE, EDAP and DCEP.
In recent decades, more and more recognition has received Thalidomide, as a preparation of salvation. At the heart of its mechanism of action is the oppression of pathological angiogenesis. There is also evidence of a successful combination of Thalidomide with polychemotherapy regimens, Melfalan and Dexamethasone. Therefore, this combination in high doses can successfully replace VAD before autologous transplantation. In addition, there is no need for long-term treatment with daily infusions to avoid thrombosis. As a rule, Thalidomide is tolerated by patients safely. Most often, constipation, drowsiness and peripheral neuropathy are noted. But the derivatives of this drug do not have such side effects, except for myelosuppression.
Among the anti-angiogenic drugs in the treatment of myeloma, the drug is isolated, which is based on cartilage shark. It is used in a purified form and inhibits cancer angiogenesis.
Also, as a treatment for this severe and complex disease, a proteasome inhibitor of bortezomib is used. This drug directly inhibits proliferation and induces apoptosis in malignant cells. Also, it does not allow interacting processes between myeloma cells and microenvironment, inhibits molecular adhesion on the cell surface.
An effective drug in the treatment of myeloma is arsenic trioxide. In addition to destroying tumor cells, it stimulates molecules that are located on the cells of myeloma, which helps to recognize them in the immune system.
High-dose therapy with subsequent stem cell transplantation is mainly used to treat patients younger than 65 years, with both primary and relapsing forms of the disease.
When planning therapy with high doses, preference is given to Dexamethasone, polychemotherapy regimens and the VAD scheme with Cisplastin. All these manipulations can be combined with thalidomide or derivatives.
Some medical scientists in 41% achieved absolute remission and 42% - partial remission after applying the total treatment method, which includes excellent induction regimens for polychemotherapy (EDAP and VAD), tandem high-dose therapy with transplantation and maintenance therapy in the form of interferon before relapse.
Myeloma is a tumor disease in which growing cells have a small fraction, i.e. their insignificant amount is in the cell cycle. This is why Interferon, which supports the body after reaching remission, is used for a long time (several years).
For prophylactic treatment of myeloma with systemic osteoporosis and osteolytic lesions, Clodronate intravenously or inwardly, Zoledronate and Pamidronate are used, which can suppress the malignant hyperactivity of osteoclasts, as well as their maturation. After long-term use of these drugs for more than one year, the bones cease to undergo resorption, bone pains decrease, fractures and hypercalcemia decrease.
Bisphosphonates are indicated in the treatment of myeloma in all patients, especially those who have lesions of bones of a lytic property, with signs of osteoporosis and bone pain. But the duration of such treatment has not yet been established. There is also evidence that bisphosphonates not only inhibit osteoclasts, but also directly exert antitumor actions on cells of a malignant disease. Also, we must always remember that bisphosphonates can have a nephrotic effect.
For the treatment of many patients with myeloma, hemosorption and plasmaphoresis are widely used, especially for hyperviscosity syndrome, renal insufficiency, and a fairly high level of paraprotein in the blood. In therapy with hypercalcemia, in addition to corticosteroids, hydration is used, and diuretics and immediate intravenous administration of bisphosphonates are prescribed.
Also, patients with myeloma are prescribed replacement transfusions of erythrocyte mass and erythropoietin preparations for anemia.
Myeloma illness forecast
Modern methods of treatment extend life to patients with myeloma mostly up to four years instead of one or two years without proper treatment.
As a rule, the life expectancy of patients depends on the sensitivity to polychemotherapeutic treatment with cytostatic drugs. Patients with primary relapse after treatment survive an average of at least a year. But with prolonged therapy with cytostatics, cases of development of leukemia of acute forms become more frequent in 5%, when this disease practically does not occur in patients who have not undergone treatment.
Of course, the life expectancy of many patients depends on the stage of the disease on which myeloma was diagnosed. In addition, life expectancy is affected by three important factors, such as urea and hemoglobin levels in the blood, as well as clinical symptoms of the patient.
The causes of death can be progressive myeloma disease, blood infection (sepsis), kidney failure, sometimes myocardial infarction and stroke.