Multiple myeloma (Myeloma)

Description:

The multiple myeloma is the malignant new growth of system of blood relating to group of paraproteinemic hemoblastoses, resulting from uncontrolled proliferation in marrow of the plasmocytes having ability to produce a large amount of monoclonal immunoglobulin (IgG, IgA, IgD, IgE) or light chains a kappa or a lambda.
Epidemiology. Incidence of a multiple myeloma makes about 40 cases on one million population. Average age of patients at the time of establishment of the diagnosis - 60-65 years, about 2% of patients is more senior than 40 years. Men are ill more often than women.

Reasons of the Multiple myeloma:

The etiology of a multiple myeloma is not known. Refer contact with radioactive materials, pesticides, benzene, some organic solutions to potential risk factors.
As a rule, the myeloma is shown by multiple lytic tumors in bones, osteoporosis and a diffusion plasmocytosis in marrow. A significant amount of pathological monoclonal immunoglobulin (myelome proteins) which is produced plasmatic by cells circulates in plasma owing to what its volume and the general viscosity of blood can increase. Myelome proteins interact with blood-coagulation factors and, enveloping thrombocytes, influence their function and strengthen bleeding.
Except myelome proteins, plasmocytes have ability also to make various cytotoxic factors, for example a factor which activates function of osteoclasts. Osteoclasts cause a resorption of a bone tissue therefore ostealgias appear, pathological changes and there is a hypercalcemia. Plasmocytes anemia of varying severity, a leukopenia and/or thrombocytopenia are a consequence of infiltration of marrow. Reduction of quantity of leukocytes and disturbance of synthesis of normal immunoglobulins can cause a depression humoral and to a lesser extent, cellular immunity that does such patients very sensitive to many infections (preferential bacterial).

Symptoms of the Multiple myeloma:

Clinical signs of a disease are rather various. Patients, as a rule, complain of constant ostealgias, a back and a waist that is combined with reduction of growth and osteoporosis (especially at men and women till the period have menopauses). The compression of a spinal cord and spinal nerves with emergence of the corresponding neurologic symptomatology (a paraparesis and dysfunction of pelvic bodies) is possible. An everyday occurrence for patients are pathological changes.
Patients with a multiple myeloma suffer from the frequent infectious complications (caused preferential Streptococcus pneumonie, Staphylococcus aureus, gram-negative microorganisms), feel low, the short wind, dizziness connected with anemia and tumoral intoxication existence of the symptoms characteristic of a renal failure is possible. Manifestations of the raised bleeding can be the investigation of a coagulopathy and thrombocytopenia. At a part of patients the asymptomatic current of a myeloma is observed, and diseases comes to light at a blood test research which is conducted in other occasion.

Diagnosis:

In the general blood test the erythrocytopenia, a leukopenia and thrombocytopenia can be noted. Special diagnostic value has increase in SOE. At a blood serum research the expressed proteinemia which arises at the expense of the increased products plasmocytes of monoclonal immunoglobulins of a certain class quite often draws attention. In urine of patients with a multiple myeloma it is possible to find a proteinuria, often positive reaction to Bens-Jones's protein (we will note that this reaction is not pathognomonic for a myeloma and can be observed at others of morbid conditions).
X-ray inspection of bones of a skeleton (a thorax, a basin, a skull, humeral and a femur, a backbone) allows to find in them the centers of a resorption of a bone tissue and osteoporosis. About it it is necessary to remember that the specific radiological characters characteristic of a multiple myeloma, do not exist. Lack of osteodestructions does not exclude a disease, and their existence is considered insufficient for confirmation of the diagnosis.
Verification of the diagnosis of a multiple myeloma requires carrying out a sternal puncture with the subsequent calculation of a miyelogramma, allowing to establish plazmokletochny infiltration of marrow. However at multiple and focal forms of a disease when diffusion damage of marrow is not observed, the miyelograma can be normal. In the presence of other signs of a multiple myeloma (an osteodestrukiiya, a monoclonal imunoglobulinopatiya) for confirmation of the diagnosis it is necessary to appoint repeated punctures of a breast in different places, a trepanobiopsiya of an ileal bone, to carry out punctures in places of bone tumors, at controversial issues carrying out a resection of the affected bone is possible (edges, shovels).
The diagnosis of a multiple myeloma is considered reliable at set of the following signs:
1. The quantity of plasmocytes in marrow> / = 10% and/or is established presence of a solitary plasmacytoma which is confirmed by means of a biopsy.
2. Identification of monoclonal protein in a blood plasma and/or urine (if the monoclonal protein is not found, then quantity of plasmocytes in marrow has to exceed 30%).
3. Calcium level in blood - on the upper bound of norm or above, a renal failure (creatinine> of 20 µmol/l), anemia (hemoglobin less than 100 g/l), the destruction centers in bones or osteoporosis (if there is only osteoporosis, then for confirmation of the diagnosis it is necessary to have more than 30% of plasmocytes in marrow).

Treatment of the Multiple myeloma:

Treatment of patients with a multiple myeloma consists in carrying out the chemotherapy directed to fight against a tumoral clone and in correction of the complications connected with disease (an anemia syndrome, a syndrome of a resorption of a bone tissue, a renal failure, etc.).
It should be noted that the condition of patients who have no clinical symptoms of a disease, the normal level of hemoglobin and calcium in plasma is not present disturbances as kidneys and a syndrome of a resorption of bones, can remain stable for a long time ("smoldering", or a "lazy" myeloma) and not to demand specific treatment. Such patients, however, need to have careful medical examination and a research of a paraprotein in plasma and urine каждык 3 months.
To patients at whom the disease has the expressed clinical signs or progressing of a disease is observed, it is necessary to conduct chemotherapy courses.
Most often at the first stage of treatment to patients Melphalanum combination with Prednisolonum is appointed. As a rule, such scheme is acceptable for patients of advanced age which does not plan performing high-dose therapy with autotransplantation of marrow. Melphalanum apply in a dose 6-8 mg/sq.m a day together with Prednisolonum in a dose of 40-60 mg/days within 4-7 days with 4-6 weeks intervals. Treatment continues before achievement of the maximum response to treatment (only 9-12 months). Such medical scheme allows to reach reduction of level of a paraprotein by 50% at 50% of patients within several months. Duration of positive effect from treatment is equal 18-24 months, average life expectancy of the patients who are treated according to this scheme  increases for 2-4 years. Continuation of chemotherapy after achievement of a stable phase of a disease (a plateau phase) does not influence remission duration. Full remissions are reached seldom. It is necessary to consider that Melphalanum needs to be applied with care at patients with a renal failure.
Enough widely used the VAD protocol is. At treatment under this protocol use Vincristinum and adriamycin within 4 days continuous infusion in combination with oral administration of dexamethasone in a high dose. Takoe treatment allows to reach considerable percent of full remissions (60-70% for a short period). The VAD protocol has not value influence on stem cells and is the ideal mode, is applied before autotransplantation. At the same time performing such treatment has the considerable shortcomings connected with need of use for infusion of himiopreparat of the central venous catheter that can cause emergence a catheter - the associated infection and coagulative complications.
Pulse therapy by dexamethasone in a dose of 40 mg a day within 4 days with a 4-day break in treatment is also considered rather effective method of treatment for the first time of the revealed multiple myeloma. The medical answer makes 40-50% and more, the positive answer is observed after several cycles. However pulse therapy by dexamethasone has many side effects, analogical subjects which arise at use of high doses of glyukokortikosteroidny hormones (disturbance of mood, sleeplessness, irritability, disturbances of attention, a liquid delay in an organism, increase in weight, steroid diabetes, gastrointestinal frustration, infectious complications, weakness of proximal muscles, decrease in sight, including development of a cataract).
In certain cases to patients the combined polychemotherapy is appointed (the Sq.m protocols, AVSM, etc.). As a rule, use of a combination from several himiopreparat has no considerable advantages before the schemes stated above, but increases toxic impact on an organism of patients.
Patients who did not answer positively therapy of the first line are considered as potential candidates for performing autotransplantation of peripheral stem cells.
With the subsequent autotransplantation it is considered high-dose chemotherapy one of enough effective modern methods of treatment of a multiple myeloma (full remission is reached at 24-75% of patients, partial remission - at 76-90%), however this method finally does not cure this pathology (in more than 90% of patients in the future is exposed to palindromias). Average life expectancy at patients after the carried-out high-dose therapy makes 4-5 years, the bezretsedivny period lasts about 18-24 months. The mortality connected with the procedure of transplantation low (about 1%). Autotransplantation is not shown to patients of advanced age (70 years are more senior) and those who has the serious accompanying pathology.
Presently there are no accurate recommendations of purpose of therapy by the patient which reached remission. Within research protocols for this purpose most often apply Prednisolonum, alpha interferon, studying of efficiency of use of a thalidomide is conducted.
For effective treatment of bone defeats at a multiple myeloma appointment from the very beginning of adequate chemotherapy and, if necessary, radiation of bones is extremely important. Radiation of bones is appointed at a compression of a spinal cord, a long strong pain syndrome, for treatment and a preduprzhdeniye of pathological changes.
For the purpose of acceleration of process of a reparation of a bone tissue purpose of bisfosfonat - a pamidronat (Аредиа), zoledronovy acid (Zomet), clodronate (Бонефос) is recommended. The Aredia is applied intravenously once in 3-4 weeks in a dose of 120 mg and it is considered the safest drug for patients with a renal failure. One of the best drugs among representatives of this group for correction of a hypercalcemia is Zometa. Drug is used in a dose of 4 mg in the form of 15-minute infusion of times in 3 - 4 weeks. Бонефос apply in the form of intravenous 2-hour infusion in a dose 300 mg a day within 7 days as the alternative method of treatment can be used oral administration of drug - 1600 mg a day.
New method of treatment of destructions of a backbone is use of a kofoplastika with administration of liquid cement that allows to strengthen a rachis and to reduce a pain syndrome. To patients at whom pathological changes are not revealed, moderate exercise stresses, especially swimming and walking are recommended.
For correction of the syndrome of anemia accompanying with a multiple myeloma use iron preparations, B12 vitamin (in cases of the accompanying deficit of these elements), carry out packed red cells transfusion. Also for treatment of anemia pathogenetic purpose of erythropoetin is reasonable (Epreks, Rekormon, etc.). At the first stage at treatment erythropoetins apply "loading by a dose" when the drug is administered in a dose of 40 000 units in a week. If after 4 weeks of administration of drug in the specified dose there was no increase in hemoglobin, the dose of erythropoetin raises to 60 000 units. Therapy continues until the level of hemoglobin does not increase up to 120 g/l, and stops at hemoglobin of 140 g/l. The maintenance therapy is carried out by erythropoetin three times a week in a dose of 10 000 units with increase in a dose in case of need to 20 000 units.
Important component of treatment of patients with a myelome nephropathy is sufficient hydration, transfusions of alkaline solutions and плазмафарез. At patients with a renal failure it is necessary to limit use of nephrotoxic drugs (intravenous contrasts, aminoglycosides, ванкомидин, Amphotericinum In, an acyclovir, cyclophosphamide, diuretics, bisfosfonata - except for an aredi).
When carrying out chemotherapy at patients from a renal nedostatnistyyu advantage in treatment should be provided to protocols and dexamethasone as monotherapy as they provide bystry medical effect without additional toxic influence on kidneys as it can be observed in a case with Melphalanum.
The reason of infectious complications at patients with for the first time the established myeloma, as a rule, Streptococcus pneumoniae, Hemophilus inflrnse, Herpes zoster. It is established that infectious complications meet in the first 3 months from an initiation of treatment and during the disease recurrence more often. During this period the patient with a myeloma prescription of antibiotics and streptocides (for example, Biseptolum) for the purpose of prevention of infectious complications is possible. Treatments of a bacterial infection it is carried out by the general principles of a rational antibioticotherapia taking into account nephrotoxicity of separate drugs.
Modern therapy promotes extension of life of patients with a myeloma. Average life expectancy at adequate treatment makes 50 months.