Myeloma is a malignant proliferation of mature differentiated plasma cells, accompanied by increased production of monoclonal immunoglobulins, infiltration of the bone marrow, osteolysis and immunodeficiency. Disease occurs with pain in the bones, spontaneous fractures, the development of amyloidosis, polyneuropathy, nephropathy and CRF, hemorrhagic diathesis. The diagnosis is confirmed by the data of radiography of the skeleton, complex laboratory examination, bone marrow biopsy and trepanobiopsy. In myeloma, mono- or polychemotherapy, radiation therapy, bone marrow autotransplantation, plasmocytoma removal, symptomatic and palliative treatment are performed.
Myeloma (Rustitsky-Kaler’s disease, plasmocytoma, multiple myeloma) is a disease from the group of chronic myeloblastic leukemias with a lesion of the lymphoplasmocytic series of hematopoiesis, leading to the accumulation of abnormal immunoglobulins of the same type in the blood, violation of humoral immunity and destruction of bone tissue. Pathology is characterized by a low proliferative potential of tumor cells affecting mainly bone marrow and bones, less often – lymph nodes and lymphoid tissue of the intestine, spleen, kidneys and other organs.
Pathology accounts for up to 10% of cases of hemoblastosis. The incidence of myeloma disease averages 2-4 cases per 100 thousand population and increases with age. As a rule, patients over 40 years old are ill, children – in extremely rare cases. Representatives of the Negroid race and males are more susceptible to myeloma.
The causes of myeloma have not been clarified. Quite often, different types of chromosomal aberrations are determined. There is a hereditary predisposition to the development of myeloma. The rise in morbidity is associated with the influence of radiation exposure, chemical and physical carcinogens. Disease is often detected in people who have contact with petroleum products, as well as in tanners, carpenters, farmers.
The degeneration of lymphoid germ cells into myeloma begins in the process of differentiation of mature B-lymphocytes at the level of proplasmocytes and is accompanied by stimulation of a certain clone of them. The growth factor of myeloma cells is interleukin-6. In this disease, plasmocytes of various degrees of maturity with atypical features are found, differing from normal ones in large size (>40 microns), pale coloration, multinucleation (often 3-5 nuclei) and the presence of nucleoles, uncontrolled division and a long life span.
The proliferation of myeloma tissue in the bone marrow leads to the destruction of hematopoietic tissue, inhibition of normal sprouts of lymph and myelopoiesis. The number of erythrocytes, leukocytes and platelets in the blood decreases. Disease cells are not able to fully perform the immune function due to a sharp decrease in the synthesis and rapid destruction of normal antibodies. Tumor factors deactivate neutrophils, reduce lysozyme levels, and disrupt complement functions.
Local bone destruction is associated with the replacement of normal bone tissue by proliferating myeloma cells and stimulation of osteoclasts by cytokines. Foci of bone tissue dissolution (osteolysis) form around the tumor without osteogenesis zones. Bones soften, become brittle, a significant amount of calcium enters the blood. Paraproteins, entering the bloodstream, are partially deposited in various organs (heart, lungs, gastrointestinal tract, dermis, around joints) in the form of amyloid.
According to the type and prevalence of tumor infiltrate, local nodular form (solitary plasmocytoma) and generalized (multiple myeloma) are distinguished. Plasmocytoma more often has bone, less often – extra-bone (extramedullary) localization. Bone plasmocytoma is manifested by a single focus of osteolysis without plasmocellular infiltration of the bone marrow; soft tissue – a tumor lesion of lymphoid tissue.
Multiple myeloma is more common, it affects the red bone marrow of flat bones, the spine and the proximal sections of long tubular bones. It is divided into multiple-nodular, diffuse-nodular and diffuse forms. Taking into account the characteristics of myeloma cells, plasmocytic, plasmoblastic, and low-grade (polymorphocellular and small-cell) myeloma are isolated. Myeloma cells excessively secrete immunoglobulins of the same class, their light and heavy chains (paraproteins). In this regard, immunochemical variants of myeloma are distinguished: G-, A-, M-, D-, E- myelomas, Bence-Jones myeloma, unclassifying myeloma.
Depending on the clinical and laboratory signs, 3 stages of myeloma are determined:
- I – with a small tumor mass;
- II – with an average tumor mass;
- III – with a large tumor mass.
Myeloma in the preclinical period proceeds without complaints of poor health and can only be detected by laboratory blood testing. Symptoms of myeloma are caused by bone plasmocytosis, osteoporosis and osteolysis, immunopathy, impaired kidney function, changes in the qualitative and rheological characteristics of blood.
Usually, multiple myeloma begins to manifest itself with pain in the ribs, sternum, spine, collarbones, shoulder, pelvic and femoral bones, spontaneously arising during movements and palpation. Spontaneous fractures, compression fractures of the thoracic and lumbar spine are possible, leading to shortening of growth, compression of the spinal cord, which is accompanied by radicular pain, impaired sensitivity and motility of the intestine, bladder, paraplegia.
Myeloma amyloidosis is manifested by damage to various organs (heart, kidneys, tongue, gastrointestinal tract), cornea, joints, dermis and is accompanied by tachycardia, cardiac and renal insufficiency, macroglossia, dyspepsia, corneal dystrophy, joint deformity, skin infiltrates, polyneuropathy. Hypercalcemia develops in severe course or terminal stage of myeloma and is accompanied by polyuria, nausea and vomiting, dehydration, muscle weakness, lethargy, drowsiness, psychotic disorders, sometimes coma.
A frequent manifestation of the disease is myeloma nephropathy with stable proteinuria, cylindruria. Renal insufficiency may be associated with the development of nephrocalcinosis, as well as with AL-amyloidosis, hyperuricemia, frequent urinary tract infections, hyperproduction of the Bence-Jones protein, leading to damage to the renal tubules. With myeloma, Fanconi syndrome can develop – renal acidosis with impaired concentration and acidification of urine, loss of glucose and amino acids.
Myeloma is accompanied by anemia, a decrease in erythropoietin production. Due to pronounced paraproteinemia, there is a significant increase in ESR (up to 60-80 mm / h), an increase in blood viscosity, and a violation of microcirculation. With myeloma, an immunodeficiency condition develops, and susceptibility to bacterial infections increases. Already in the initial period, this leads to the development of pneumonia, pyelonephritis, which have a severe course in 75% of cases. Infectious complications are one of the leading direct causes of mortality in myeloma.
Hypocogulation syndrome in myeloma is characterized by hemorrhagic diathesis in the form of capillary hemorrhages (purpura) and bruises, bleeding from the mucous gums, nose, digestive tract and uterus. Solitary plasmocytoma occurs at an earlier age, has a slow development, is rarely accompanied by damage to the bone marrow, skeleton, kidneys, paraproteinemia, anemia and hypercalcemia.
If myeloma is suspected, a thorough physical examination, palpation of painful areas of bones and soft tissues, chest and skeleton radiography, laboratory tests, aspiration biopsy of the bone marrow with a myelogram, trepanobiopsy are performed. Additionally, the levels of creatinine, electrolytes, C-reactive protein, b2-microglobulin, LDH, IL-6, and plasmocyte proliferation index are determined in the blood. Cytogenetic study of plasma cells, immunophenotyping of mononuclear blood cells is carried out.
In multiple myeloma, hypercalcemia, an increase in creatinine, a decrease in Hb < 100 g / l, and a proliferation index > 1% are noted.. With plasmocytosis >30% in the absence of symptoms and bone destruction (or its limited nature), they speak of a sluggish form of the disease.
The main diagnostic criteria for myeloma are atypical plasmatization of the bone marrow > 10-30%; histological signs of plasmocytoma in trepanate; the presence of plasma cells in the blood, paraprotein in urine and serum; signs of osteolysis or generalized osteoporosis. Radiography of the chest, skull and pelvis confirms the presence of local areas of rarefaction of bone tissue in flat bones.
An important stage is the differentiation of myeloma with benign monoclonal gammapathy of uncertain genesis, Waldenstrom’s macroglobulinemia, chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, primary amyloidosis, bone metastases of colon cancer, lung, osteodystrophy, etc.
Treatment and prognosis
Treatment of myeloma begins immediately after verification of the diagnosis, which allows prolonging the patient’s life and improving its quality. With a sluggish form, a wait-and-see tactic with dynamic observation is possible until the clinical manifestations increase. Specific therapy of myeloma is carried out when target organs are affected (so-called CRAB hypercalcemia, renal insufficiency, anemia, bone destruction).
The main method of treatment of multiple myeloma is long–term mono- or polychemotherapy with the appointment of alkylating drugs in combination with glucocorticoids. Polychemotherapy is more often indicated in stages II, III of the disease, stage I of Bence-Jones proteinemia, progression of clinical symptoms.
After treatment of myeloma, relapses occur within a year, each subsequent remission is less achievable and shorter than the previous one. To prolong remission, maintenance courses of a-interferon drugs are usually prescribed. Complete remission is achieved in no more than 10% of cases.
In young patients, in the first year of detection of myeloma after a course of high-dose chemotherapy, autotransplantation of bone marrow or blood stem cells is performed. With solitary plasmocytoma, radiation therapy is used, providing long-term remission, if ineffective, chemotherapy is prescribed, surgical removal of the tumor.
Symptomatic treatment of myeloma is reduced to correction of electrolyte disorders, qualitative and rheological parameters of blood, hemostatic and orthopedic treatment. Palliative treatment may include painkillers, pulse therapy with glucocorticoids, radiation therapy, prevention of infectious complications.
The prognosis of myeloma is determined by the stage of the disease, the patient’s age, laboratory parameters, the degree of renal insufficiency and bone lesions, and the timing of the start of treatment. Solitary plasmocytoma often recurs with transformation into multiple myeloma. The most unfavorable prognosis for stage III B of myeloma is with an average life expectancy of 15 months. At stage III A, it is 30 months, at stage II and I A, B – 4.5-5 years. With primary resistance to chemotherapy, survival is less than 1 year.