Multiple myeloma - a disease lymphoproliferative nature, which are the morphological substrate of plasma cells that produce monoclonal immunoglobulin.Multiple myeloma disease or multiple lesions considered neoplastic diseases of the lymphatic system with a low degree of malignancy.For the first time in our country the disease was described in 1949 by GA Alekseev.
Multiple myeloma is about 1% of all malignant cancer pathology, and among Leukemia - 10%.And the people of the black race suffer much more frequently than others, although the disease occurs among all races.Multiple myeloma mainly affects people after forty years.
Today, the disease is often denoted plasmacytoma and multiple myeloma.This concept includes disseminated tumor process of B-lymphocytes, which are composed of plasma cells reborn.Multiple myeloma is based on the development of the most important features, such as laboratory and clinical, and complications that include myeloma cell infiltration in the bone
Multiple myeloma causes
Currently etiology of multiple myeloma is not yet clear.However, it is proved that myeloma develops as a result of ionizing radiation, which is considered a factor in the alleged aetiological involvement in the emergence of the disease.Ig apply to most of globulins, which are produced by malignant plasma cells after antigenic stimulation.Any such cell can synthesize a single epitope with lambda or kappa light chain.
Uncontrolled process of synthesis of monoclonal M protein leads to malignant transformation of individual progenitor cells.It is believed that myeloma produces these cells, which may be pluripotent stem cells.This disease is characterized multiple chromosomal abnormalities such as monosomy thirteenth chromosome, trisomy third, fifth, seventh, ninth, eleventh, fifteenth and nineteenth chromosome.Very often, there are disturbances in the structure of the first chromosome having no specific defect.
changes from tumor progenitor cells occurs before clinical symptoms characteristic stage, which lasts for twenty, sometimes thirty years.The plasma cell malignancy held, able to penetrate into the kidneys, bone and form the symptoms of multiple myeloma in the form of widespread multifocal neoplastic process.In some cases, cancer cells divide and proliferate locally, which gives rise to the development of solitary plasmocytomas.These tumors are formed as a result of the secretion of M-protein, which subsequently causes in causing overt clinical myeloma.
etiological factors in the formation of multiple myeloma associated with the proliferation of abnormal plasma cells nature.This process occurs mainly in the bone marrow and sometimes with foci of extramedullary lesion.Animal studies confirm that in the development of neoplastic plasma cells participate environmental and genetic factors.But the role of these factors in humans has not been proved.There is also information about cases of familial multiple myeloma, but the exact evidence of its susceptibility at the genetic level in humans, too, is no.
Thus, in the etiology of multiple myeloma assumed the role of the two factors.Typically, this ionizing radiation and mutation in progenitor cells.
Multiple myeloma symptoms
For clinicians myeloma its many manifestations poses quite a challenge.Symptoms of the disease is divided into symptoms that are usually associated with local tumor localization, as well as the impact of the products of malignant cells.These are the metabolites and monoclonal immunoglobulins properties.
In 70% of the first symptom of myeloma is marked bone pain, which is characterized by acute onset of local and caused minor injuries, but no fractures.Typically, the pain migrates through the body, it can sometimes disturb the patient at night and occur after a change in body position.Very often, the pain may occur in the chest, however, lesions may affect the pelvic and long tubular bones.
Education joint pain speaks of amyloidosis.To a certain stage of the disease is characterized by the occurrence of a mandatory anemia, which occurs as a result of the characteristic weakness and fatigue occurs rapidly.
Multiple myeloma is rarely characterized by symptoms such as weight loss and fever.However, these symptoms appear in an advanced degree of severity, and after joining the infection.In 7% of patients having bleeding complications in the form of multiple myeloma.At the onset of the disease is detected hypercalcemia, which is caused by vomiting, constipation, thirst, polyuria accession confusion and sometimes even coma.Multiple myeloma can begin renal failure, which very quickly becomes oliguria and needs immediate hemodialysis.
physical nature of the changes may be in the beginning of the disease minimal.Patients marked by pallor of the skin and a lack of work of the heart, resulting in a small amount of bone marrow.In the areas defined by palpation ostioliza bumpy and painful bone surface.After compression of the spinal cord or nerve damage due to fractures or spine, as well as various deposits is bone appears sciatica, paraplegia, impaired motor skills, and lost control of the sphincters.Very rare hepatosplenomegaly with moderate enlargement of the liver in 26%.
Quite often detected bone disease at the time of clinical presentation.Based on X-ray in 80% of multiple myeloma affects bone.The deformation of the bones leads to osteoporosis generalized, osteolysis with single or multiple foci, to the kind of fracture and damage that can capture and surrounding soft tissues.Most minor injuries cause various fractures.It is also very common lesions undergo pelvic bones and skulls, vertebrae and ribs.With the defeat of multiple myeloma mandibular fracture occurs in the course of its food.
One of the dangerous complications of the disease is considered to be a violation of the kidneys.This dysfunction is detected in half of the patients at diagnosis of multiple myeloma and is the underlying cause of lethal outcome in patients.Renal function refers to the single most important factor that determines the prognosis of multiple myeloma.The basis for these disturbances of the kidneys can lie different mechanisms that lead to the development of renal failure in acute or chronic, or cause nephrotic syndrome, Fanconi syndrome.And, moreover, symptoms of hyperuricemia, hypercalcemia and increased formation of blood viscosity.Increases in serum levels of calcium, and polyuria, and vomiting, leading to loss of water.
Multiple myeloma is characterized by lesions of the nervous system as a result of penetration of the pathological process in the nerve or spinal cord processes, as well as a consequence of hypercalcemia or blood viscosity.Sometimes you can see the symptoms of polyneuropathy resulting in amyloidosis.Almost 30% of the observed state of compression of the spinal cord and cauda equina lesion.Radiculopathy develops after the spread of the pathological process with the vertebrae in the extradural space character.Very often there are specific back pain that precede paraplegaliyam.As a result of compression there is a weakness in the muscles lose sensitivity, impaired urination, which leads to paresis.
most often multiple myeloma is localized in the department of chest that manages to establish with the help of X-ray and tomographic examinations.
Neuropathy peripheral localization is very rare.And if it joins amyloidosis, developing carpal tunnel syndrome.You can also find sensorimotor peripheral neuropathy properties in the form of a stocking-glove.It can manifest itself in the absence of amyloid deposits such as;occur against the backdrop of the solitary lesion or multiple foci of multiple myeloma.There is some connection between neuropathy and osteoskleroticheskimi changes, and polycythemia, skin pigmentation and thickening of phalanges.At these moments increased protein in the cerebrospinal fluid.As a result of the defeat of multiple myeloma skull bones develop paralysis of the nerves cranial departments, and with the defeat of the orbit bone broken oculomotor function and optic nerve, followed oftalmoplegaliey.
In 10% of patients with the syndrome, multiple myeloma occurs macroglobulinemia.It is a syndrome of increased viscosity causes bleeding from the nose and gums.Also, patients often lose their sight, and the most constant symptom of the disease is retinopathy.It is characterized by bleeding flaming nature, veins, which extended and tortuous, retinal vein thrombosis, puffiness of the optic nerve.Neurological symptoms are very rich.It can begin in the form of drowsiness, pain in the head or dizziness, and then move on to conditions such as loss of consciousness and coma.
In 20% of observed hypercalcemia that occurs when bone resorption by osteoclasts.This is evident lack of appetite, stomach disorders such as nausea, vomiting and constipation.Much later, there drowsiness to confusion, turning into a coma.Polydipsia and polyuria develops and then the calcium deposited in the kidneys, there is dehydration, which can become a cause of renal failure.
15% at melomnoy disease appears as a complication of bleeding.
Very often, multiple myeloma reduces the ability to confront infections.Almost half of the patients at different stages of the disease developed a severe form of infectious complications, which causes frequent cases of death.The most common are urinary tract infections and respiratory system, to the agents which include H. influenzae, pneumococcus, meningococcus, intestinal bacteria, and the herpes virus.
Multiple myeloma stage
Currently no generally recognized staging system for S.Salmon and B.Durie, which is based on the dependence of the mass of malignant cells from the laboratory and clinical performance characteristics and prognosis of multiple myeloma.
Currently, there is another system, which is based on determination of parameters such as β2-microglobulin and serum albumin.First, in this case, it is a low molecular weight protein that is produced by nuclear cells and is excreted in the urine.For indirect serum albumin characteristic of IL-6 and osteoklastaktiviruyuschego growth factor.The same system of steps in multiple myeloma offered IMWG, which is an international group in the study of this disease.
When using the classification of multiple myeloma immunochemical properties are five forms of the disease: Bence-Jones, A, E, G, and D. Among the rare forms can be isolated and non-secretory myeloma M.50% G-myeloma detected in 25% - A myeloma, 1% - D-myeloma rest against occur in small and rarely.
stage multiple myeloma depends on the mass of the tumor focus.Therefore, this disease is characterized by three pathological stage of the disease.Weight of tumor cells to 0.7 mg / m 2 (low) characteristic of the first stage of myeloma, from 0.7 to 1.3 mg / m 2 (average) - the second stage, more than 1.3 mg / m 2 (high)- the third stage.
Multiple myeloma diagnosis
for diagnosis are three main criteria.As a rule, first of all, necessary to identify the clonal plasma cells, using a myelogram, and the plasma cell tumor biopsy material from the affected fire.Second, determine the monoclonal lg in serum and urine.Third, detect signs of tissues and organs that have a connection with multiple myeloma: hypercalcemia, renal failure, anemia, osteoporosis or bone Lysis pockets.
When diagnosing multiple myeloma special role belongs to an existing plasma cell tumor lesions.This makes it possible to identify patients with active disease or symptomatic manner.
for the diagnosis of multiple myeloma use X-rays of the skull bones, collarbone, sternum, shoulder blades, ribs, all departments of the spine, pelvis, hip and shoulder bones, and other parts of the skeleton as clinically indicated.Biochemical examination of blood to determine the total protein, albumin, calcium, creatinine, uric acid, alkaline phosphatase, lactate dehydrogenase, transaminase, and bilirubin.In general, the analysis of blood count differential blood count and platelet count.Radial immunodiffusion to determine level of immunoglobulins in the blood.Electrophoresis is used to identify densitometry.
also collected urine for general analysis and Zimnitsky, to determine the loss of protein in the urine daily.And to identify the level of paraprotein immunofixation using proteins and electrophoresis.More
use additional diagnostic techniques such as MRI of the whole spine, cytogenetic studies, immunophenotyping of cancer cells.
Multiple myeloma treatment
In the first stage (A) with indolent form of multiple myeloma treatment does not require immediate treatment.Only with the appearance of enlarged paraprotein, hemorrhagic and hyperviscous syndromes, with the progression of osteolytic nature, such as bone pain, spinal cord compression and spinal pathological fractures, hypercalcaemia, disruption of kidney amyloidosis, anemia syndrome, and complications such as infection, startdestination specific treatment.
When compression of the brain in the spinal canal is performed laminectomy and kyphoplasty in treatment of dexamethasone, local irradiation, and pathological fractures are used orthopedic fixation.
method of radiation therapy in multiple myeloma is considered a palliative treatment of locally located lesions, especially when expressed pain.Dosage of irradiation is from 20 Gy to 24 for two weeks in five - seven sessions.For the treatment of solitary plasmocytomas prescribed total dosage of 35 to 50 Gy.Basically beam radiation is used to treat the affected cranial bones in the face and the base.
The main methods of treatment of patients with a diagnosis of multiple myeloma is chemotherapy with tsiklonespetsificheskih funds, especially alkylating agents such as cyclophosphamide, melphalan supported by corticosteroids.It is also important to consider that all alkylating drugs may give rise in the future, mielodispaticheskogo syndrome or acute form mieloleykemii.In addition, the accumulated toxic effects on bone marrow, which violate the production of stem cells, may interfere in the conduct of an autologous transplant.
most commonly used for the treatment of patients with chemotherapy regimens such as Protocol No. 2, alternating - VMCP / VBAP and AB / CM.However, the conventional treatment of multiple myeloma Alkeran and prednisone, as well as the schemes of chemotherapy does not exceed five per cent to achieve the absolute remission and disappearance of paraprotein in blood and urine.