A reliable average inverse correlation was established between a decrease in the excursion of the diaphragm during forced and quiet breathing and an increase in AHDLA in patients II (r = –0.59; P <0.05 and -0.51; P <0.05) and III (r = – 0.66; P <0.01 and – 0.61; P <0.05) groups. A strong positive correlation was found between a decrease in the MOVP of the sum and a decrease in the pO 2 of blood in patients of the II (0.86; P <0.001) and III (0.9; P <0.001) groups. The inverse correlation relationship between the decrease in blood pO 2 and the increase in SrDLA in patients of the II (r = –0.65; P <0.01) and III (r = –0.9; P <0.001) groups was diagnosed. Smaller correlation coefficient and reliability in group II is explained by insignificant changes in pO 2 indices in these patients. and SrDLA. It can be concluded that a violation of the functional capacity of the diaphragm leads to impaired ventilation of the middle and lower zones of the lungs, as a result of which hypoxemia and PH develop.

A significant increase in the liver and spleen, which occurs in many patients with a progressive course of CLL and in the terminal stage of the disease, contributes to a high standing of the diaphragm case and disruption of its excursion. The diaphragm is the main respiratory muscle, which, under physiological conditions, provides 2/3 of the vital capacity of the lungs, and 70–80% of inspiration with forced respiration [208]. So, according to J.L. Shika and V.I. Sobolev, as a result of the movement of the diaphragm, the lower and 40-50% of the ventilation volume of the upper lobes of the lungs is fully ventilated. Violation of the excursion of the diaphragm, the main respiratory muscle, is an important factor in the violation of respiratory function in the late stages of tumor progression in patients with CLL. Compression of the lower parts of the lungs with enlarged liver and spleen is an important factorreducing respiratory volume lower zones and redistribution of ventilation in the upper zones of the lungs. It can be argued that mechanical compression of the diaphragm with enlarged liver and spleen and its specific leukemic lesion contribute to impaired contractility of the diaphragm, which is one of the reasons for the development of hypoxemia and PH in patients with CLL II group without an associated broncho-obstructive process. This group included a greater number of patients with the splenic CLL.

Other causes of hypoxemia and PH in patients with CLL in stage B are a decrease in microhemocirculation and a severe, prolonged course of infections of the bronchopulmonary system, accompanied by impaired ventilation and hemodynamics of the pulmonary circulation.

In the later stages of tumor progression of CLL, the lymph nodes in the chest cavity acquire a dense texture, lymphoid infiltration appears in the lungs and pleura (with the development of specific lymphoproliferative pleurisy), a compression syndrome develops, leading to impaired bronchial patency and pulmonary ventilation, as a result of the pulmonary pulsations of the pulmonary pulmonary regimen. – gain a heavy and long current. These changes contribute to a decrease in pO2 and an increase in pressure in the aircraft system. This explains the higher value of SrDLA in patients of group III. As CLL progresses, myocardial dystrophy develops in such patients, which contributes to impaired hemodynamics of the ICC and an increase in pressure in the PA.

Thus, four mechanisms of LH development in patients with CLL who do not have a concomitant bronchial obstruction process can be distinguished: 1) thoracodiaphragmatic due to decreased excursion of the diaphragm, when it is compressed with enlarged liver and spleen and leukemic lesion 2) bronchopulmonary – severe and prolonged course of infectious and specific leukemic processes; 3) vascular due to impaired blood rheology in the vessels of the ICC; 4) myocardial degeneration.

For the first time, a comprehensive examination of the bronchopulmonary system (spirography, traditional X-ray, regional lung rheography) was performed in 1997 (at that time stage B according to the Binet classification was at that time). On radiographs and tomograms, an increase in mediastinal lymph nodes was determined. No other pathology was identified.

In 2006, the patient was diagnosed with stage J. according to J. Binet’s classification: hemoglobin – 75g / l, erythrocytes – 2.6 × 10 12 / l, platelets – 70 × 10 9 / l, leukocytes – 280 × 10 9 / l, lymphocytes – 98%, segmented – 2%; marked lymphadenopathy – lymph nodes of all groups up to 3-4 cm in diameter, with a densely elastic consistency; splenomegaly was the leading clinical syndrome — the spleen occupied the entire left half of the abdominal cavity; the liver was significantly enlarged .

As a result of a comprehensive examination of the bronchopulmonary system of patient A. in 2006, the following changes were diagnosed. With CT of the lungs – a significant increase in lymph nodes in the chest cavity, the high position of the dome of the diaphragm. During spirography, there were no impairments in the ventilation function of the lungs. During peak flow measurements, the PSV indicators were as follows: in the morning hours – 96% D, in the evening hours – 101% D. During pneumotachography, an increase in bronchial inhalation resistance was observed (3.3 cm.vod.st / l / s) and on exhalation (3.6 cm.v.st./l / s). When fibrobronchoscopy was diagnosed with bilateral diffuse endobronchitis, IV Art. LDF data: PM – 23.09 PE, σ – 10.89 PE, Kv – 47.16%, Ae – 6.2 PE, An – 3.93 PE, Am – 3.18 PE, Ad – 2.7 PE, Ac – 1.6 PE.

During the 13-year study period, a fatal outcome was found in 95 CLL patients. The mortality of patients with CLL was analyzed and morphological changes in the lungs, bronchi, and pleura in these patients were studied according to autopsy data. The terminal stage of CLL is more often manifested by the transformation into a large cell lymphosarcoma, the development of cachexia. Prolymphocytic crisis was observed in only two patients. Blast crisis CLL in our study is not registered. The immediate causes of death of patients with CLL are given.

Histological examination of autopsy material showed lymphoid infiltration of the lungs and bronchi in 43 patients (45%). However, only 5 patients had massive leukemic infiltration, which was radiologically detected in the form of focal or infiltrative shadows, and then the diagnosis was made after long-term follow-up of the disease and exclusion of other local processes in the lungs. In the same patients, lymphoid infiltration was diagnosed macroscopically at autopsy. Histological examination of the lungs in these situations revealed a total monomorphic leukemic infiltration along the interalveolar septa, filling the lumen of the alveoli and vessels with lymphocytes . In all other cases, lymphoid infiltration was detected only with microscopic Optical research . Lymphoid infiltration in the lungs was predominantly interstitial. Often, in the stage of malignant transformation, there was a total infiltration of the interstitial lung tissue. Lei goat infiltration was very pronounced along the bronchi, small vessels and in the interalveolar septa, often it was of a confluent nature. Hemorrhages were observed in the interstitial and respiratory tissue with a perivascular edema. Foci of leukemic infiltration in respiratory structures were less frequently observed.

Histological examination in the lungs showed an expansion and congestion of blood vessels, the lumens of many vessels were filled with lymphocytes (leukostasis) . Leukostasis was especially frequently detected in small-caliber vessels. The accumulations of lymphocytes in these situations completely blocked the gaps of small vessels, causing a significant disruption of microcirculation . In some patients, infiltration of the walls of the pulmonary vessels with tumor cells and multiple perivascular arteries of lymphoid cells were noted.

Peribronchial, perivascular, interstitial sclerosis was revealed in many patients. Multiple atelectasis of the lung tissue alternated with areas of emphysematous dilatation of the alveoli, as well as edema and sclerosis of the interalveolar septa . In patients with CLL, it is possible to express an assumption about the compensatory nature of the localized pulmonary emphysema. In some areas, in the presence of diffuse lymphoid infiltration of the pulmonary tissue and an increase in bronchopulmonary lymph nodes, alveoli are excluded from ventilation due to atelectasis. A decrease in the area and ventilation capacity of other alveoli due to edema, sclerosis of the interalveolar septa, lymphoid infiltration of the interalveolar septa, desquamation of the alveolar epithelium is noted. In the remaining parts of the lung, the expansion of the alveoli occurs compensatory. These changes are more pronounced in CLL patients in the later stages of the tumor progression. Speaking of emphysema in patients with CLL, it is also necessary to take into account the elderly age of most patients,in this case, senile emphysema may occur.

Morphometric studies were conducted in patients who died in the presence of CLL. When performing a morphometric study of the bronchi and alveoli, a comparative analysis was carried out with similar indicators of 30 absolutely healthy people, equal in age and sex, who died from injuries incompatible with life and who did not have a history of hemoblastosis and bronchopulmonary pathology (control group).

A morphological study of segmental bronchi in patients with CLL showed a decrease in the number of neutrophils, eosinophils, plasma and mast cells in the submucosal layer. In patients who died due to the progression of CLL, an increase in the number of lymphocytes at all levels of the bronchial tree was observed. In most patients, the height of the mucosal epithelium and the thickness of the mucous membrane of the segmental bronchi were significantly reduced. In many patients, thinning of the basement membrane is noted, and growth of connective tissue in the submucosal layer. Atrophic changes of the mucous membrane should be explained by a violation of endobronchial microhemocirculation, which largely depends on the extent of leucostasis .

The walls of many vessels of the bronchopulmonary apparatus in patients with CLL, compared with the control group, looked somewhat thickened due to edema and lymphoid infiltration. Dilation of the vessels of the lungs and bronchi, some of which was filled with lymphocytes, was noted. The ratio of vascular diameter to thickness in patients with CLL was 12.9 ± 0.05, in the control group it was slightly lower – 11.8 ± 0.04. The degree of vascular plethora was changed, in CLL patients (67 ± 2.7%) it was higher than in the control group (55.3 ± 3.7%; P <0.05).

The thickness of the interalveolar septa in many of the dead was increased due to their edema (55 ± 5.2 compared to 40 ± 0.08 μm in the control; P <0.01). Due to the large number of emphysematous transformed tissue in patients with CLL, an increase in the area of ​​the alveoli is observed (172 ± 28 μm 2 ), but due to the large variability of this indicator, this increase, compared with the control, was not significant (132 ± 10 μm 2 ; P> 0.05).

Specific lymphoproliferative pleurisy was diagnosed in 21 patients. 19 found to be fatal. In cytological examination of exudate, lymphocytes were found in a large number of these patients. Histological examination revealed diffuse or focal lymphoid pleural infiltration .

The study of the diaphragm in 45 patients with a significant increase in the liver and spleen revealed the predominance of myocytes of medium size (cross-sectional area – 501 ± 14.2 μm 2 ), but there was an increase in the newly formed large myocytes (1969 ± 31 μm 2 ) and small (286, 8 ± 17 microns 2 ) sizes. Necrobiotic changes in myocytes were diagnosed . In these patients, a significant growth of stroma was observed around the vessels and the intermuscular space. Revealed large areas lipomat Oz . Such dystrophic changes are caused by dysfunction of the diaphragm, due to its compression with enlarged liver and spleen. A histological examination showed lymphoid and filtration of the diaphragm and lymphocytic stasis in the vessels, which also contributes to the violation of the contractile ability of the diaphragm and dystrophic changes in muscle fibers. In 30 patients there was no significant increase in the liver and spleen. The sizes of myocytes of the diaphragm in such patients did not have significant differences with those of practically healthy individuals, without concomitant bronchopulmonary diseases and hemoblastosis, who died from injuries (96% were also average myocytes) . However, many patients without severe hepato – and splenomegaly showed lymphoid infiltration of the diaphragm and accumulation of lymphocytes in the lumen of the vessels. Lymphoid infiltration of the diaphragm has never reached a size where it could be determined macroscopically, in all cases these were histological findings.

An enlarged lymph nodes in the chest cavity was detected in 73 (76.8%) deaths from CLL (according to the data of an intravital radiological study of 228 patients with CLL, an increase in the lymph nodes in the chest cavity was diagnosed in 66.7% of patients). At the same time, an increase in mediastinal lymph nodes was observed in 65 patients, aortic arches in 30 people, paratracheal in 10, paraesophageal in 8, bifurcation in 12, bronchopulmonary in 65 cases.

In 14 patients, the enlarged bronchopulmonary lymph nodes appeared in the form of large packages, dense, rocky consistency, were brazed into conglomerates and caused compression, infiltration, and lung tissue and bronchi. Histological analysis of these lymph nodes revealed signs of transformation into large-cell lymphosarcoma (Richter syndrome). In all these patients, death occurred when pneumonia was added. For patients who died without obvious signs of sarcoma transformation, compression syndrome in the chest cavity is not typical. The lymph nodes of the mediastinum, even with a significant increase, remained soft consistency and did not squeeze the surrounding tissue.

Leukostasis in vessels with CLL is not clinically determined, as a rule [237]. But as mentioned earlier, their presence explains the impaired microhemocirculation , which contributes to the development of morphological changes in the bronchi and lungs, a severe and prolonged course of inflammatory processes of the bronchopulmonary system. In order to identify statistically significant indicators that could indicate the presence of leukostasis in the pulmonary vessels, a discriminant analysis was carried out for which the statistical package STATISTIKA 6.0 was used. The study included patients who did not have a concomitant pulmonary disease. All this sick a full instrumental examination of the bronchopulmonary system was performed in vivo, and after autopsy, morphological changes in the lungs and bronchi were studied. The results of discriminative analysis are as follows:

Statistically significant signs (P <0.05): 1) Leukocytosis in peripheral blood is more than 100 × 10 9 / l (p = 0.0001); 2) Reduction of PM during endobronchial LDF less than 50 PE (p = 0.001); 3) Reduction of Ac when performing endobronchial LDF less than 2.5 PE (p = 0.0015); 4) Reducing Hell when conducting endobronchial LDF less than 2.5 PE (p = 0.0025); 5) prolonged and recurrent infections of the bronchopulmonary system (bronchitis, pneumonia) (p = 0.032); 6) B – symptoms, p = 0.035.

The combination of the above indicators with a high degree of probability may indicate the presence of leucostasis in the vessels of the microcirculatory bed of the bronchopulmonary system in patients with CLL. As it was established by previous studies, the risk of developing leukostasis occurs with an increase in leukocytosis more than 50 × 10 9 / l, with leukocytosis more than 200 × 10 9 / l, they almost always develop . The decrease in the microhemocirculation parameter, the amplitudes of oscillations in the cardiac and respiratory ranges in CLL is largely due to the presence of leucostasis in the vessels of the microvasculature. “B” symptoms (fever, night sweat and weight loss) in CLL appear in the later stages of tumor progression, when the tumor process gets out of control of cytostatics and progressive leukocytosis is observed in the blood. In these patients, a prolonged and recurrent AML is observed.

Statistically insignificant signs: 1) A decrease in hemoglobin of less than 100 g / l (p = 0.2); 2) Increase in bronchopulmonary lymph nodes according to CT data (p = 0.28); 3) Reduction of the total MPKr index during lung rheography of less than 50 ohms / min (p = 0.9).

In CLL, a decrease in the hemoglobin level can be caused not only by bone marrow infiltration with tumor cells with crowding out all the hemopoiesis sprouts, but also autoimmune conflict. An enlarged lymph node, including bronchopulmonary, is not always accompanied by high leukocytosis in the peripheral blood. In the rheographic method of studying pulmonary blood flow, pulsatory vibrations of large vessels are detected. Therefore, these indicators for the diagnosis of leukostasis in the vessels of the lungs and bronchi are not reliable.

Classifying functions: Group1 = -1.21-0.57 * X1-1.62 * X2 + 0.87 * X3 + 1.77 * X4 + 0.74 * X5 + 1.07 * X6 + 0.63 * X7 + 1.05 * X8 + 1.46 * X9. Group 2 = -86.8 + 46.5 * X1 + 41.1 * X2 + 32.2 * X3 + 25.5 * X4 + 39.2 * X5- 9.7 * X6 + 4.7 * X7-2 , 8 * X8 + 1.9 * X9.

The obtained classification functions can be used to assign a patient to group 1 or group 2. For this indicator values ​​obtained from the newly admitted patient, are entered into the classification functions for groups 1 and 2. The classification functions are calculated, and the patient relates to the group for which the calculation gave a greater value.

As an example, here is an extract from the case history No 12368. Patient S., born in 1940. Diagnosis: Chronic lymphocytic leukemia, splenic form, stage C according to the classification of Binet. The diagnosis was made in 2002, death was ascertained in 2006.

Clinical research data from 2005. Peripheral lymph nodes of all groups up to 2 – 3 cm in diameter, soft-elastic consistency. The spleen is significantly enlarged, occupies the entire left half of the abdomen. The lower edge of the liver is palpable 14 cm below the right costal arch. Blood count: hemoglobin – 106 g / l, erythrocytes – 3.3 × 10 12 / l, platelets – 50 × 10 9 / l, leukocytes 150 × 10 9 / l, lymphocytes – 80%, segmented core – 12% , eosinophils – 3%, monocytes – 5%.Immunophenotyping of peripheral blood lymphocytes – CD5 +, CD19 +, CD20 +, CD22 +, CD23 +. Radiographic examination of the chest: mediastinal lymph nodes are not enlarged, the high position of the diaphragm dome. These endobronchial LDF: PM – 23.8 PE, σ – 11.7PE, Kv – 45.1%, Ae – 6.1 PE, An – 3.5 PE, Am – 3 PE, Hell – 2.4PE, Ac – 1.65 PE. When conducting a regional rheography, MOVr (soum) -70 ohm / min, MPKr (soum) – 65 ohm / min.

During the discriminant analysis, the following data was available: leukocytosis> 100 × 10 9 / l (1), PM <50 PE (1), Reduction of Ac <2.5 PE (1), Reduction of Ad <2.5 PE (1 ), relapsing and protracted AML (1), B-symptoms (1), MPKr <50 ohms / min (0), Decrease in hemoglobin <100 g / l (0), increase in bronchopulmonary lymph nodes at CT (0 ).

The following classification functions were calculated: Group 1 = -1.21-0.57 * 1-1.62 * 1 + 0.87 * 1 + 1.77 * 1 + 0.74 * 1 + 1.07 * 1 +0, 63 * 0 + 1.05 * 0 + 1.46 * 0 = 2.19. Group 2 = -86.8 + 46.5 * 1 + 41.1 * 1 + 32.2 * 1 + 25.5 * 1 + 39.2 * 1-9.7 * 1 + 4.7 * 0- 2.8 * 0 + 1.9 * 0 = 88.0.

As can be seen from the calculation results, the value of the classifying function for group 2, equal to 88.0, is greater than the value of the function for group 1. Consequently, the patient was assigned to group 2, the combination of the listed symptoms most likely indicated the presence of leucostasis in the vessels of the lungs and bronchi.

Morphological study of the lungs, bronchi and diaphragm after autopsy. Histological examination revealed lymphoid infiltration of the interstitial lung tissue. The lymphoid infiltration of the bronchi of all calibers was diagnosed. The foci of tumor infiltrates were determined in the peribronchial tissue. Marked dilation and congestion of blood vessels, the lumens of many vessels were filled with lymphocytes with the formation of leucostasis. Hemorrhages in the intestine and respiratory tissue were observed. Multiple atelectasis of the pulmonary tissue alternated with areas of emphysematous enlargement of the alveoli. There were abnormalities and sclerosis of interalveolar septa, peribronchial, perivascular, interstitial sclerosis. The mucous membrane of the bronchi over a considerable distance was thinned, sclerosed,the preserved epithelium is partially metaplaced into a stratified flat. The diaphragm thickness is 3.7 mm. Myocytes have prevailedmedium sized. However, there was a marked increase in myocytes of large and small sizes (15.2 and 39.1%), a significant growth of the stroma around the vessels, in the intermuscular space, and large areas of lipomatosis. Lymphoid infiltration of the diaphragm and lymphocytic stasis in small vessels was revealed.

After analyzing and comparing data from studies of regional ventilation and pulmonary blood flow with X-ray and morphological studies of the bronchopulmonary system in CLL patients, it was concluded that the functional disorders of the respiratory system are directly dependent on the morphological changes in the lungs, bronchi and diaphragm in these patients in different stages of tumor progression. In the process of tumor progression of hemoblastosis, lymphoid infiltration of the lungs and bronchi appears, in the lungs pneumosclerosis, localized emphysema, is noted. As a result, there is a morphological change in the alveoli and a violation of their functional ability. There is a significant violation of endobronchial microhemocirculation, one of the reasons for which is high leukocytosis,contributing to the formation of leukostasis in the vessels of the bronchopulmonary system. Disorders of microhemocirculation are progressing with the development of anemic syndrome. As a result, trophic tissue suffers. The metabolism in cells of a mucous membrane of a bronchial tube is broken. Thinning, hardening of the mucous membrane occurs. Against this background, due to pronounced immunodeficiency, an inflammatory process joins. In 60% of patients with progressive CLL, there is a latent course of chronic non-structural bronchitis. Excursion of the diaphragm is reduced due to its compression by significantly enlarged liver and spleen and specific leukemic lesions. The hemodynamics of a small circle of blood circulation is broken. All of the above leads to impaired general and regional ventilation and lung perfusion.In addition to the above, the progression of impaired lung ventilation in the terminal stage of CLL is facilitated by the sarcoma of the lymph nodes of the mediastinum with the development of compression syndrome, hemorrhage into the lung tissue and bronchi due to the development of thrombocytopenia.

Decreases in regional ventilation and pulmonary blood flow account for a decrease in pO2 during tumor progression of CLL. Severe and protracted obstructive processes in the bronchi, restrictive processes in the lungs, impaired function of the diaphragm and hemodynamics of the ICC, pathology of the microvasculature, contribute to the development of hypoxemia and pulmonary hypertension. Therefore, in the process of tumor progression of CLL, the pressure in the system of the pulmonary artery increases.

By prevalence in the Amur region MM is located on the 5th place . In the general structure of hemoblastosis MM takes 9.8%. Since the mid-1990s, there has been an increase in the incidence of MM, if in 1994 it was 0.5 per 100,000 of the population, then in 2004 it was 1.7 per 100,000 of the population. The average annual incidence of MM for the period studied was 1.4 per 100,000 population. The distribution of patients with MM by age at the time of detection of the disease is presented in Table 23. The average age is 57 ± 5.8 years. There was a slight predominance of men over women (52 and 48%, respectively).

In the study of immunochemical variants of MM, it was found that myeloma G is most often detected – 72 people (58.5% of the total number of patients with MM), less often Myeloma A – 27 people (22%), Bens-Jones myeloma – 11 people (9% ), non-secretory myeloma – 1 3 patients (10.5%) .

The study of clinical and anatomical features of myeloma showed that diffuse – focal (80 people – 65%), diffuse (18 people – 14.6%) and multiple – focal (16 people – 13%) forms of MM . Solitary myeloma was diagnosed in 8 patients (6.5%). The diagnosis of predominantly visceral form of MM is made for 1 patient (0.9%).

When diagnosing the disease, 31 patients (25.1%) were diagnosed with stage IA, 12 (9.8%) stage IIA, 55 (44.7%) stage IIA. In 25 patients at the time of diagnosis, myeloma nephropathy was detected, complicated by chronic renal failure: IB stage was diagnosed in 3 (2.4%), IIB in 5 (4.1%), IIIB in 17 (13.9%) patients (table 24). Staging was carried out according to the B. Durie and S. Salmon classification [310].

For the treatment of solitary myeloma, radical surgical or / and radiation treatment was used, chemotherapy was not performed. Further, in 4 patients , generalized myeter myeloma was noted . In 10 patients with “smoldering ” myeloma , a waiting tactic prevailed . When signs of growth of the tumor mass appeared, chemotherapy was prescribed. The life expectancy of patients with “smoldering” myeloma is 10–15 years.

For patients with stage I, the median survival was 79 months, regardless of the treatment protocol. In the group of patients with stage IIA, the median survival was 47.6 months for patients treated with the MP protocol, for patients treated with the 1st line polychemotherapy protocols (M 2 -VBMCP, AVBMCP, VMCP / VBAP, ABCMP, CBMP, AVMP, ABCM) 53 months. In the group of patients with stage IIIIA, the median survival was 33.9 months for patients treated with the MP protocol – 50 months for patients treated with the 1st line polychemotherapy protocols. Since the polychemotherapy protocols of the reserve (VAD, VAMP, VCAD, CEVAD, pulsotherapy with dexamethasone, etc.) were performed in patients with aggressive MM with primary and secondary resistance to other protocols, the survival rate of such patients rarely exceeded 36 months.

Since the spring of 2006, Velcade (bortezomib) has been used in the hematology department of the Amur Regional Clinical Hospital for the treatment of recurrent and resistant forms of MM. As a second-line therapy, treatment with this drug was carried out in 20 patients with MM. In 13 cases, a recurrence of the disease occurred, in 7 patients, primary resistance to therapy was ascertained. In 17 cases, IIIA occurred, in 3 cases, stage IIIB (according to B. Durie and S. Salmon, 1975). The duration of illness of patients taken for bortezomib treatment ranged from seven years to six months. Depending on the age and somatic status of the patients, velcade was administered both as monotherapy and in combination with other cytostatics — VMP protocols (velcade, melphalan, prednisolone), Velc + dexa (velcade and dexamethasone),PAD (velcade, dexamethasone and adriablastin). All patients are currently undergoing the necessary treatment. In 4 patients, a fatal outcome was noted due to the progression of the underlying disease. In 10 patients managed to reach the phase of “plateau”. In 6 patients, complete remission of the disease was achieved. Complete remission in MM patients, prior to the use of velcade, during chemotherapy, was achieved extremely rarely, in most cases only after autologous bone marrow transplantation. It is particularly encouraging that complete remission was achieved in patients with a disease duration of more than 5 and 7 years. Combineddue to the progression of the underlying disease. In 10 patients managed to reach the phase of “plateau”. In 6 patients, complete remission of the disease was achieved. Complete remission in MM patients, prior to the use of velcade, during chemotherapy, was achieved extremely rarely, in most cases only after autologous bone marrow transplantation. It is particularly encouraging that complete remission was achieved in patients with a disease duration of more than 5 and 7 years. Combineddue to the progression of the underlying disease. In 10 patients managed to reach the phase of “plateau”. In 6 patients, complete remission of the disease was achieved. Complete remission in MM patients, prior to the use of velcade, during chemotherapy, was achieved extremely rarely, in most cases only after autologous bone marrow transplantation. It is particularly encouraging that complete remission was achieved in patients with a disease duration of more than 5 and 7 years. Combinedin most cases, only after autologous bone marrow transplantation. It is particularly encouraging that complete remission was achieved in patients with a disease duration of more than 5 and 7 years. Combinedin most cases, only after autologous bone marrow transplantation. It is particularly encouraging that complete remission was achieved in patients with a disease duration of more than 5 and 7 years. Combinedtherapy was much more effective than bortezomib monotherapy. Of the 6 patients in whom complete remission was achieved, four received combination therapy.

Since June 2008, in the hematology department of the Amur Regional Clinical Hospital, Velcade has been used as a first-line therapy in combination with other drugs (protocols VMP, Velc + dexa, PAD). To date (September 2009), 7 patients have been assigned as first-line therapy. In all patients, therapy started in stage IIIA of the disease. Complete remission was achieved in 2 and partial remission in 3 people, the minimum response in one patient. In this case, three patients have not completed the full course of treatment. Only one patient admitted to the ward with the presence of multiple visceral lesions has a progression of the disease.

All patients had two side effects of the drug: peripheral sensory neuropathy of the 2nd and 3rd degrees and thrombocytopenia. More rarely, they were diagnosed: intestinal paresis, exacerbation of chronic pancreatitis, reduced visual acuity. In all patients, the common side effects of chemotherapy were noted – weakness, loss of appetite, and increased fatigue. Complications were amenable to correction, and there was an opportunity to continue therapy.

In this study, there was no registered worse tolerance of polychemotherapy protocols compared to monotherapy with Velcade. However, no protocols containing high doses of dexamethasone (PAD, Velc + dexa) were prescribed to patients with severe cardiovascular diseases and diabetes mellitus. Considering the better and more durable clinical effect of the polychemotherapy courses, compared with Velcade monotherapy, it was concluded that it is advisable to administer combined therapy, including bortezomib, to patients with the first diagnosed MM (except for cases of “smoldering” myeloma), in the absence of severe concomitant pathology.

As a symptomatic therapy in the treatment of MM, plasmapheresis was used with high protein content in serum; with deep anemia transfusion of red blood cell mass, erythropoietin. Local radiation therapy was carried out in the presence of limited tumor nodules in the bones, severe compression syndrome, the threat of pathological fractures. Bisphosphonates were used to prevent and treat hypercalcemia, to improve the repair of bone destruction.

Patients have not established a connection in life expectancy with age less than 70 years, gender, type of monoclonal secretion. Survival of patients primarily depended on the sensitivity of the tumor to chemotherapy and on the stage at the time of detection of the disease. The effect of the following indicators on the overall survival of patients was established: 1) myeloma nephropathy complicated by chronic renal failure (median survival was 16 months); 2) severe pancytopenia, diagnosed in the debut of the disease; 3) mielemia in the debut of the disease; 4) age over 70 years due to the presence of severe concomitant pathology in most such patients and poor tolerance to cytostatic therapy; 5) plasmocytosis in the bone marrow> 40% with unripe plasmablast morphology of plasma cells;6) increase in lactate dehydrogenase (> 300 IU / l), β – microglobulin (> 60 mg / l) in the blood.

The main cause of death in most cases was the presence of myeloma nephropathy, complicated by chronic renal failure (CRF). Less often, death occurred due to the addition of infectious complications, hemorrhagic , anemic syndromes, the presence of concomitant cardiovascular pathology in patients with MM.

Since the majority of patients with MM are patients over the age of 50 years, many have associated comorbidity, often influencing the course of the underlying disease .

Group I consisted of 43 patients with IA and IIA stages of the disease. Patients of this group lacked or had single focal bone destruction, the hemoglobin level was above 85 g / l, normal serum calcium level and a low level of the M-component were observed (Ig G <70 g / l or Ig A <50 g / l; protein BJ <12 g per day). All patients with solitary myeloma and “smoldering myeloma” were included in this group. Analyzing the immunochemical variants of MM patients in group I, 27 patients with myeloma G, 13 with non-secreting myeloma, 2 with myeloma A and 1 with Bence-Jones myeloma should be noted. The average age of patients of group I was 56 ± 4.6 years.

Group II included patients in stage IIIA of the disease (55 people). A pronounced osteodestructive process was characteristic of these patients. The level of the M-component was high: Ig G> 70 g / l or Ig A> 50 g / l; protein BJ> 12 g per day. Characterized by anemia (HB <85 g / l), hypercalcemia. The average age of patients in this group was 58 ± 6.5 years. In the majority of patients of group II, there was a developed clinical picture of MM with the presence of bone marrow, hypercalcemic, anemic, hemorrhagic syndromes, syndromes of increased blood viscosity, antibody deficiency, neurological manifestations, etc. This group included 33 patients with myeloma G, 17 with myeloma A and 5 with myeloma Bens-Jones.

Group III consisted of 25 patients in whom myeloma nephropathy and chronic renal failure (stages IB, IIB, IIIB) had already occurred during the initial diagnosis of MM. The average age of patients in group III was 57 ± 6.6 years. Most of this group included patients in Stage III with multiple bone destruction, severe anemic syndrome, high paraprotein secretion. Only in 8 people the myeloma nephropathy was the leading syndrome, in the absence of a pronounced osteo-destructive process in the bones, satisfactory indicators of red blood and serum calcium level. Group III included 12 people with myeloma G, 8 with myeloma A, and 5 with myeloma Bens-Jones.

The control group consisted of 30 people without hemoblastosis and AML. The 2nd control group included 25 patients with pneumonia. The 3rd control group included 25 patients with COPD.

The clinical characteristics of the bronchopulmonary system in patients with MM, without exacerbation of AML, depended on the stage of tumor progression. Patients of group I had no osteodestructive syndrome. In patients of this group who did not abuse smoking and who did not have concomitant bronchopulmonary pathology, the chest was regular in shape, painless on palpation, percutaneous over the entire lung surface was determined by a clear pulmonary sound, during auscultation listened to vesicular breathing, adverse respiratory sounds not noted.

Patients of group II are characterized by a pronounced osteodestructive syndrome, including in the bones that form the chest. In 24 patients of group II, percussion over the entire lung surface was determined clear pulmonary sound, vesicular breathing was heard, there were no side respiratory sounds. In 10 patients with a significant deformation of the chest, who were in a forced position during percussion and auscultation of the lungs, the changes were interpreted as interpreted as manifestations of circulatory failure, emphysema, and pulmonary fibrosis; lower parts of the lungs. In 8 patients, MM was complicated by myelomatous lesion of the pleura with the development of exudative pleurisy; in the affected area, weakening of breathing, dulling of the pulmonary sound, and increased voice tremor were observed.

In 17 patients with MM of group III (stage IIIB), a pronounced osteo-destructive process of the chest occurred. In 8 people (IB and stage IIB), the osteodestructive syndrome was absent. In patients with MM of group III, with the initial manifestations of renal failure, with percussion and auscultation of the lungs there were no significant violations. In the terminal stage of chronic kidney disease, all had nephrogenic pulmonary edema. Clinical manifestations of nephrogenic edema were shortness of breath, bouts of shortness of breath, or choking with increased respiration, occurring with a rapid increase in body weight. During bouts of nephrogenic edema, a boxed shade of percussion sound or shortening of sound over the lower parts of the lungs and in the interscapular region was determined. Auscultation noted weakened or hard breathing, dry scattered rales, less often moist fine wheezing, with uremic lesions of the pleura – pleural friction noise (5 patients).

All 123 patients with multiple myeloma were x-rayed. The study began with traditional radiography of the lungs in two projections or large-frame x-ray of the chest, later on, when detecting pathological changes in the lungs, ERTG and CT were performed.

In the majority of cases (72 people — 58.5%), when conducting traditional X-ray diffraction, interstitial changes were detected: increased vascular pattern, pneumosclerosis and emphysema. Radiographic signs of damage to the intestinal lung tissue were more often recorded in patients with stage III disease, especially in the presence of myeloma nephropathy and renal failure. Very rarely, interstitial changes were found in the early stages of tumor progression (IA, IIA stages according to the classification of B. Durie and S. Salmon, 1975). Gain and deformation of the pulmonary pattern in MM is explained by stagnation of blood in small vessels and the development of pneumosclerosis, since blood flow in the pulmonary capillaries is slowed down due to increased plasma viscosity. Analyzing the group of patients with MM with interstitial changes in the lungs, it was found that in most cases these were patients over the age of 50 years (52 people — 72.2% of the total number of patients with interstitial changes in the lungs), with pronounced monoclonal secretion (G or A) and high serum total protein content (45 people – 62.5%). In 25 patients with interstitial changes in the lungs, renal failure was diagnosed (34.7%).