Myeloma, myeloma: symptoms, treatment, prognosis

Myeloma belongs to the group of paraproteinemic hematological malignancies in which the malignant transformation of plasma cells is accompanied by hyperproduction of their abnormal proteins of immunoglobulins. The disease is relatively rare, the average sick 4 persons on 100 thousand population. It is believed that men and women are equally prone to tumors, but, according to some, women get sick more often. In addition, there are indications of a greater risk of myeloma among the blacks of Africa and the United States.

The average age of patients ranges between 50 and 70 years that is the bulk of the patients are elderly people, who, in addition to myeloma, there are other pathology of the internal organs, which significantly worsens the prognosis and limits the use of aggressive therapies.

Myeloma is a malignant tumor, but it is a mistake to call it by the term «cancer», because it is not from the epithelium, and hematopoietic tissue. The tumor grows in the bone marrow, and its basis is formed by the plasma cells. Normally, these cells are responsible for immunity and formation of antibodies, needed to fight different infectious agents. The plasma cells originate from b-lymphocytes. In violation of the ripening of cells appears tumor clone, which gives rise to myeloma.

Under the influence of adverse factors in the bone marrow an increased reproduction plazmoblastov and plasma cells that acquire the ability to synthesize abnormal proteins are detectable. The same proteins are considered to be immunoglobulins, but to fulfill their immediate protective function, they are not able, and their greater number leads to blood clots and damage to internal organs.

Миелома, миеломная болезнь: симптомы, лечение, прогноз

The proven role of the various biologically active substances, in particular interleukin-6 in patients elevated. Stromal bone marrow cells engaged in supportive and nutritive functions (fibroblasts, macrophages) secrete interleukin-6 in large quantity, resulting in active proliferation of tumor cells, inhibited their natural death (apoptosis) and the tumor is actively growing.

Other interleukins are able to activate osteoclasts, cells that destroy bone tissue, so bone lesions is so characteristic of myeloma. While under the influence of interleukins, myeloma cells acquire an advantage over healthy, displace them and other sprouts of hematopoiesis, resulting in anemia, impaired immunity, bleeding.

In the course of the disease there are chronic and acute.

  • In chronic stages of multiple myeloma cells do not tend to reproduce quickly, and the tumor does not leave the limits of the bone, patients feel well, and sometimes do not suspect about the beginning of tumor growth.
  • Progression of myeloma, there will be additional mutations in tumor cells, resulting in the emergence of new groups of plasma cells, capable of rapid and active division; the tumor beyond the bone and begins his active settlement of the body. The defeat of the internal organs and inhibition of hematopoiesis germs lead to serious symptoms of intoxication, anemia, immunodeficiency, which makes the acute stage of the terminal disease that could lead to the death of the patient.

The main violations in multiple myeloma believe the pathology of the bones, immune deficiency and the changes associated with the synthesis of a large number of abnormal immunoglobulins. The tumor affects the pelvis, ribs, spine, in which there are processes of tissue destruction. Involvement of the kidneys can lead to chronic failure, which is quite typical for patients suffering from myeloma.

Causes of multiple myeloma

The exact causes of myeloma continue to be studied, and a considerable role in this belongs to genetic studies designed to find genes, mutations of which can lead to cancers. So, in some patients, marked activation of certain oncogenes, and the suppression of suppressor genes that block tumor growth.

Миелома, миеломная болезнь: симптомы, лечение, прогноз

There is evidence of the ability of tumor growth with prolonged contact with petroleum products, benzene, asbestos, and about the role of ionizing radiation, says the increase in the incidence of multiple myeloma among the people of Japan who suffered the atomic bombing.

Among the risk factors scientists note:

  • Old age – the vast majority of patients crossed the age of 70 and only 1% younger than 40 years;
  • Race – black population of Africa suffers from myeloma is almost twice as often as whites, but the reason for this phenomenon was never established;
  • Family history.
  • The selection of types and stages of tumors reflects not only the peculiarities of its growth and forecast, but also determine a treatment plan, which will choose a doctor. Myeloma can be a solitary when one focus of tumor growth within bone and can be uncustomarily the proliferative neoplasias, and multiple, in which the lesion is generalized.

    Multiple myeloma is capable to formation of lesions in various bones and internal organs, and depending on the nature of the prevalence of it is nodular, diffuse and multi-nodular.

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    Morphological and biochemical features of tumor cells determine the priority of the cellular composition of the myeloma – plasmocytoma, plasmablast, small cell, polymorphonuclear cell. The degree of maturity of tumor clones affect the rate of growth of the malignancy and aggressiveness of the disease.

    Clinical symptoms, features of bone pathology and disorders of protein spectrum of blood to determine the allocation of clinical staging of multiple myeloma:

  • The first stage of myeloma is relatively favorable, when it has the highest life expectancy of patients with good response to treatment. This stage is characterized by: the level of haemoglobin more than 100g/l, absence of bone lesions and, as a consequence, the normal concentration of calcium in the blood. The tumor mass is small, and the number of allocated paraprotein may be small.
  • The second stage has no strictly defined criteria and is exposed when the disease can not be attributed to the other two.
  • The third stage reflects tumor progression and occurs with a significant increase in calcium level due to the destruction of bone, hemoglobin drops to 85 g/l or less, and the growing tumor mass produces a significant amount of tumor paraprotein.
  • Level indicators such as creatinine, reflects the degree of metabolic disorders and disorders of the kidney, which affects the prognosis, therefore, in accordance with its concentration each stage is divided into podstudio and when the creatinine level is less than 177 mmol/l (A) or above stage IB, IIB, IIIB.

    Manifestations of myeloma

    Clinical signs of multiple myeloma are varied and fit into different syndromes – and-bone pathology, immune disorders, pathologies of blood coagulation, increased blood viscosity, etc.

    Миелома, миеломная болезнь: симптомы, лечение, прогноз

    the main syndromes in multiple myeloma

    The development of the expanded picture of the disease is always preceded by an asymptomatic period which can take up to 15 years, while the patients feel well, go to work and doing the usual things. About tumor growth may indicate a high sedimentation rate, unexplained appearance of protein in the urine and the so-called M-gradient in electrophoresis serum proteins, indicating the presence of anomalous immunoglobulins.

    The growth of the tumor tissue, the disease progresses and symptoms appear first disadvantage: weakness, fatigue, dizziness, and possible weight loss and frequent respiratory infections, bone pain. These symptoms it becomes difficult to stack in age-related changes, so the patient goes to a specialist who can put an accurate diagnosis on the basis of laboratory studies.

    Bone lesions

    Syndrome lesions of the bones, is a popular choice in the clinic multiple myeloma, as neoplasia in them begins to grow and leads to destruction. It first affects the ribs, vertebrae, sternum, pelvic bones. Such changes are typical for all patients. The classic manifestation of myeloma consider the presence of pain, tumor and fractures.

    Pain syndrome are experiencing up to 90% of patients. Pain as the growth of the tumor become quite intense, bed rest does not bring relief, patients may have difficulties with walking, movement of limbs, the bends. Severe pain can be a symptom of fracture, the occurrence of which is enough even a slight movement or just depression. In the area of the hearth of tumor growth, the bone breaks down and becomes very brittle, flattened vertebrae, and are susceptible to compression fractures, and the patient may experience decreased growth and visible tumor nodules on the skull, ribs and other bones.

    Миелома, миеломная болезнь: симптомы, лечение, прогноз

    the bone destruction in myeloma

    Against the background of myeloma bone disease is osteoporosis (bone thinning), which also contributes to pathological fractures.

    Disturbances in the hematopoietic system

    At the very beginning of multiple myeloma appear violation of hematopoiesis associated with the growth of the tumor in the bone marrow. At first, clinical signs can be erased, but with time it becomes obvious anemia, the symptoms of which are paleness of skin, weakness, shortness of breath. The displacement of the other germs of hematopoiesis leads to a deficiency of platelets and neutrophils, so hemorrhagic syndrome and infectious complications are not uncommon in myeloma. A classic symptom of myeloma is the acceleration of the ESR, which is characteristic even for the asymptomatic period of the disease.

    Syndrome pathology protein

    Protein pathology is considered the most important characteristics of the tumor, because myeloma is capable of producing significant amounts of abnormal protein – protein paraproteins or Bence-Jones (light chains of immunoglobulins). With a significant increase in the concentration of abnormal protein in the blood serum there is a decrease in normal protein fractions. Clinical signs of this syndrome are:

    • Persistent urinary protein excretion;
    • The development of amyloidosis with deposition of amyloid (a protein that appears in the body only in pathology) in the internal organs and the violation of their functions;
    • Hyperviscosity syndrome – increased viscosity of blood in connection with the increase in the content of protein in it, which manifests as headaches, numbness in the extremities, decreased vision, trophic changes until the gangrene, bleeding tendency.
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    Kidney damage

    Kidney damage in multiple myeloma affects up to 80% of patients. The involvement of these bodies is due to their colonization of tumor cells, deposition of abnormal proteins in the tubules and the formation of calcification when bone destruction. Such changes lead to disruption of the filtration of urine, the seal body and the development of chronic renal failure (CRF), which is often the cause of death of patients («myeloma kidney»). Chronic renal failure occurs with severe intoxication, nausea and vomiting, refusal of food, worsening anemia, and in the end it becomes uremic coma, when the body is poisoned nitrogenous wastes.

    In addition to the described syndromes, patients experience severe nerve damage with infiltration of the brain and its membranes by tumor cells, often affects the peripheral nerves, then there is a weakness, disturbance of skin sensation, pain, and the compression of the spinal roots is possible even paralysis.

    The bone destruction and leaching of calcium contribute not only to fractures, but also hypercalcemia, when the rise of calcium in the blood leads to nausea, occurrence of vomiting, drowsiness, change in consciousness.

    The growth of the tumor in the bone marrow becomes the cause of immunodeficiency States, patients prone to recurrent chest infections, pneumonia, pielonefrita, viral infections.

    End-stage multiple myeloma occurs with the rapid development of symptoms of intoxication, with worsening anemia, hemorrhagic syndromes and immunodeficiency. Patients lose weight, fever, suffer from serious infectious complications. In this stage possible transition myeloma acute leukemia.

    Diagnosis of myeloma

    Миелома, миеломная болезнь: симптомы, лечение, прогноз

    Diagnosis of myeloma involves carrying out a number of laboratory tests that allow accurate diagnosis at the first stages of the disease. Patients spend:

  • General and biochemical blood tests (hemoglobin, creatinine, calcium, total protein and fractions, etc.);
  • Determination of the level of protein fractions in the blood;
  • The urine, which increased the protein content can be identified light chain of immunoglobulin (a protein Bence-Jones);
  • Bone marrow biopsy in order to detect myeloma cells and evaluation of the nature of the defeat germs of hematopoiesis;
  • Radiography, CT, MRI bone.
  • For a correct evaluation of the results of research it is important to compare them with clinical signs of the disease, and conducting a single analysis is not sufficient for the diagnosis of myeloma.

    Миелома, миеломная болезнь: симптомы, лечение, прогноз

    histology bone marrow: normal (left) and myeloma (right)

    Treatment

    Treatment of myeloma is a haematologist at the hospital hematological profile and includes:

    • Cytostatic therapy.
    • Radiation therapy.
    • The appointment of an ALPHA2-interferon.
    • Treatment and prevention of complications.
    • Bone marrow transplantation.

    Multiple myeloma refers to an incurable tumors of hematopoietic tissue, however, timely therapy can make the swelling controllable. It is believed that recovery is possible only in case of successful bone marrow transplantation.

    To date, chemotherapy remains the main treatment for myeloma, allowing to extend the life of patients until 3.5 to 4 years. The success of chemotherapy associated with the development of the group of alkylating chemotherapy (alkeran, cyclophosphamide), which was used in combination with prednisone since the middle of last century. The purpose of chemotherapy is more effective, but survival of patients has not significantly improved. The development of chemoresistance of the tumour to these drugs leads to a malignant course of the disease, and to combat this phenomenon were synthesized fundamentally new drugs – inductors of apoptosis, proteasome inhibitors (bortezomib) and immunomodulators.

    Expectant management acceptable in patients with IA and IIA stages of the disease without pain and risk of bone fractures in ongoing monitoring of the composition of the blood, but in the case of signs of progression of the tumor cytotoxic agents are assigned is mandatory.

    Миелома, миеломная болезнь: симптомы, лечение, прогноз

    Indications for chemotherapy consider:

  • Hypercalcemia (increased calcium concentration in the serum);
  • Anemia;
  • Signs of kidney damage;
  • Involvement of the bones;
  • Development hypervigilance and hemorrhagic syndromes.
  • Amyloidosis;
  • Infectious complications.
  • The main treatment for myeloma is considered as the combination of alkeran (melphalan) and prednisone (M+P), which inhibit the proliferation of tumor cells and decrease the production of paraproteins. In case of resistant tumors, and initially severe malignant course of the disease may be chemotherapy, when additionally appointed vincristine, adriablastin, doxorubicin, in accordance with the developed chemotherapy protocols. Scheme M+R is assigned cycles every 4 weeks, and if signs of kidney failure alkeran replaced with cyclophosphamide.

    A specific program of cytostatic treatment the doctor chooses based on the characteristics of the disease, condition and age of the patient, tumor sensitivity to certain drugs.

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    The effectiveness of treatment is evidenced by:

    • Stable or rising hemoglobin level (90 g/l);
    • Serum albumin above 30 g/l;
    • Normal level of calcium in the blood;
    • The lack of progression of bone destruction.

    The use of this drug, like thalidomide, has shown good results in myeloma, especially in resistant forms. Thalidomide inhibits angiogenesis (the development of tumor vessels), enhances the immune response against tumor cells, provokes the death of malignant plasma cells. The combination of thalidomide with standard schemes of cytostatic therapy gives a nice effect and allows in some cases to avoid prolonged administration of chemotherapy, fraught with thrombosis at the site of installation of a venous catheter. In addition to thalidomide to inhibit angiogenesis in the tumor can drug shark cartilage, (neovastat), who also is appointed with multiple myeloma.

    Patients younger than 55-60 years of age is considered to be optimal conduct of chemotherapy followed by transplantation of own peripheral stem cells. This approach increases the average life expectancy of up to five years, and complete remission is possible in 20% of patients.

    The appointment of an ALPHA2-interferon in high doses is carried out at the exit of the patient in remission and is a component of maintenance therapy for several years.

    Video: lecture on the treatment of multiple myeloma

    Radiation therapy has no independent value in this pathology, but it is used for the bone lesions with large foci of destruction of bone tissue, a strong pain syndrome, solitary myeloma. The total radiation dose is usually not more than 2500-4000 Gr.

    Treatment and prevention of complications include:

  • Antibiotics drugs wide spectrum of complications of an infectious nature;
  • Correction of renal function for their deficiency (diet, diuretics, plasmapheresis and hemosorption, in severe cases – hemodialysis apparatus «artificial kidney»);Миелома, миеломная болезнь: симптомы, лечение, прогноз
  • Normalization of calcium level (forced diuresis diuretics, glucocorticoids, calcetin);
  • The use of erythropoietin, transfusion of blood components in severe anemia and hemorrhagic syndrome;
  • Detoxication therapy with the intravenous introduction of drug solutions and adequate pain relief;
  • In the pathology of the bones used calcetin, anabolic steroids, drugs from the group bifosfonatov (clodronate, zometa), which reduce the destructive processes in the bones and prevent them from fractures. At the onset of fracture are shown osteosynthesis, distraction, possible surgery, physical therapy, and preventive measure can serve as a local irradiation at the proposed location of the fracture;
  • In marked hyperviscosity syndrome and kidney pathology caused by the circulation of a significant number of neoplastic paraprotein, patients hemosorption and plasmapheresis helps to remove from the blood large protein molecules.
  • Bone marrow transplantation has not yet found widespread use in myeloma because the risk of complications remains high, especially in patients older than 40-50 years. Most transplants of stem cells taken from the patient or a donor. The introduction of the donor stem cells may even lead to a complete cure for myeloma, but this phenomenon happens rarely due to the high toxicity of chemotherapy prescribed for it in the largest possible doses.

    Surgical treatment of myeloma is rarely applied, mainly in localized forms of the disease, when the tumor mass compressing vital organs, nerve roots, blood vessels. Possible surgical treatment in the case of lesions of the spine aimed at eliminating spinal cord compression in compression fractures of the vertebrae.

    The duration of life during chemotherapy in sensitive patients up to 4 years, but a resistant form of tumor reduce it to a year or less. The highest life expectancy observed in stage IA – 61 a month, and for IIIB, it is not more than 15 months. Prolonged chemotherapy is possible not only complications related to toxic effects of drugs, but also the development of secondary resistance of the tumour to the treatment and its transformation into acute leukemia.

    In General, prognosis is determined by the shape of multiple myeloma, its treatment response and patient’s age and presence of comorbidity, but he’s always serious and remains unsatisfactory in most cases. Cure is rare and severe complications in the form of sepsis, bleeding, renal failure, amyloidosis, and toxic lesions of the internal organs on a background of application of cytostatic drugs in most cases lead to a fatal outcome.

    Video: myeloma in the program «Live healthy!»

    Video: doctors and patients about multiple myeloma