The effect of cytostatic therapy on microcirculation in patients with CLL was studied. Currently, in patients with a progressive course of CLL, in the absence of severe concomitant pathology and autoimmune complications, the treatment of choice are protocols containing fludarabine (monotherapy with fludarabine or its combination with cyclophosphamide, rituximab, mitoxantrone). The use of these protocols allows in most cases to achieve complete or partial remission of the disease. One of the criteria for complete remission is a reduction in the number of lymphocytes <4.0 × 10 9 / l, partial remission , a reduction by 50% in the number of lymphocytes of peripheral blood . In patients with groups II and III treated according to these protocols, after the normalization of the number of leukocytes, endobronchial LDF was repeated. All of them showed a significant improvement in the PM indicators, but in no case did the PM indicators completely normalize. An improvement (but not normalization) of the oscillation amplitudes in the respiratory and cardiac ranges was noted .

The persistence of endobronchial microhemocirculation disorders in patients with CLL, after achieving complete remission, is explained by the etiology of factors affecting the microcirculation indices. In addition to leukocytosis and anemia, abnormalities of platelet and plasma hemostasis, the state of the endothelium of the vessels, regulation of tissue vascular tone, pH and pO 2 , hormonal function and many other factors affect the reduction of microhemocirculation parameters .

Chlorambucil therapy, at present, is regarded only as a palliative treatment and is used in cases of a calm course of B-CLL in elderly patients with an adverse somatic status. In case of chlorambucil therapy, complete remission of CLL was not achieved in any case, leukocytosis was preserved. In patients treated with this drug, there was no significant improvement in microhemocirculation indices.

Advantage of modern CLL chemotherapy protocols (FC, FCR, FCM, etc.) when using which appeared the possibility of achieving complete remission, besides a significant reduction in the tumor mass, is an improvement in microcirculation in the vessels of the bronchopulmonary system. The restoration of microhemocirculatory blood flow contributes to the improvement of tissue trophism and, accordingly, to a decrease in the incidence of AML in CLL patients in remission.

Note: P 1 – significance of differences compared with control; P 2 – the significance of the difference between the indices of LDF, before and after achieving remission.

Thus, the study of endobronchial microhemocirculation can help predict the occurrence of inflammatory diseases of the bronchopulmonary system in patients with CLL. The informativity of the endobronchial LDF method is highly informative in diagnosing vascular and intravascular disorders of the microcirculatory bed of the bronchial mucosa, in identifying early signs of microhemocirculation disorders. The use of this method allows the assessment of the dynamics of microcirculatory disorders in the mucosa of the proximal bronchi during the treatment of CLL.

In the study of general and zonal ventilation of the lungs using the rheography method in patients of group I, no significant changes were found, compared with the control. In group II, there was a decrease in the eographical index of the respiratory volume (DOR) and the eographical indicator of the minute ventilation volume (MVD) of the middle and lower zones of both light, and an increase in the DOF and MVR of the upper zones. The total value of the MPR from all zones of the lungs was reduced by 25.9% (P <0.05) as compared with the control. The greatest changes in regional ventilation were found in patients of group III, they showed a significant decrease in dose rates and MOP in each zone of the lungs, a decrease in the total indicator of MOV from all zones of the lung, compared with controls , by 43.8% (P <0.001) . In patients with groups II and III, there was a redistribution of ventilation from the lower and middle zones to the upper zones of both lung, as can be seen from the increase in the MOVr ratio of the upper zones / MOVr of the lower zones of the lungs .

Indicators of eographically minute minute pulsatory blood flow (MCR) from each of 6 light zones in group I did not significantly differ from those of control. In patients of group II, there was a decrease in perfusion in the middle and lower zones of both lungs and its increase in the upper zones (since areas with increased ventilation are supplied with blood), the overall intensity of MPKr from all zones of the lungs is reduced by 17.4% (P <0.05). In group III, a significant decrease in perfusion was noted in the middle and lower zones of both lungs, in the upper zones, the perfusion indices did not significantly differ from the control, the total intensity of MPCr from all lung zones was reduced by 34.3% (P <0.001). In patients with groups II and III, there was a redistribution of pulmonary blood flow from the lower and middle zones to the upper zones of both lungs. . Redistribution of blood flow to the upper zones was achieved by increasing vascular resistance in the lower and middle zones of both lungs, as evidenced by a decrease in the average blood filling rate (SSC) and lengthening the a-Q interval in these zones . An important rheographic sign indicating the state of venous resistance in the pulmonary circulation is the diastolic-systolic coefficient (DSC), the highest coefficient values ​​were recorded in patients of groups II and III in the middle and lower zones of the lungs.

The development and progression of hypoxemia is associated with an increase in pressure in the pulmonary artery (LA) system. In Group I, the SrDLA indicator (14.7 ± 0.7 mm. Hg. Art.) Did not have significant differences compared with the control group (14.99 ± 0.61 mm Hg. Art.). Patients II (18.2 ± 1.08 mm. Hg. Art.) And III (22.16 ± 1.6 mm. Hg. Art.) Groups showed a significant increase in SrDLA compared with control (P <0 , 05 and Р <0.001, respectively).

EHOKG and IDKG were performed on 54 CLL patients aged from 40 to 70 years, without concomitant COPD (13 out of I, 26 out of II and 15 out of III groups). Patients with heart defects, atrial fibrillation, high blood pressure and other diseases accompanied by primary lesions of the left heart areas were excluded from the study, since this pathology has a significant impact on intracardiac hemodynamics [149, 170, 254]. In 34 patients (63%) SrD-LA indices in conditions of rest did not exceed 20 mm. Hg Art. Of these, 28 people (52%) had SrDLA values ​​within 9–16 mm. Hg Art., in 6 patients (11%) – 17 – 20 mm. Hg Art. Pulmonary hypertension (PH) was detected in 20 (37%) people. Indicators SrDL were within 21 – 32 mm. Hg St, on average – 22.5 ± 0.7 mm. Hg Art. These are patients from groups II and III, of whom 3 had progressive, 9 had tumor and 8 had splenic CLL. The highest rates of SrDLA were found in patients with splenic and neoplastic forms of CLL in the later stages of tumor progression, with a significant increase in the liver and spleen. Progressive hemoblastosis was noted in all patients with high rates of SrDLA, 6 patients were diagnosed with terminal stage of the disease.

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.

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%).

Endobronchial biopsy was performed on 10 patients of group I, 10 patients of group II and 5 patients of group III. The biopsy specimen was the same as in patients with CLL. Patients of group I were diagnosed with moderate proliferation or dystrophy of the bronchial epithelium. In patients with groups II and III, histological examination of biopsy specimens determined edema, atrophy of the bronchial mucosa, and in some cases focal squamous metaplasia of the epithelium was observed. In some patients of groups II and III, lymphocytic and plasma cell infiltration of varying severity was detected under the basement membrane. In patients of group I, there was a slight dilatation of capillaries, plethora of arterioles, capillaries and venules. Protein stasis in the vessels of the microcirculatory bed of the bronchi in patients with MM in stages IA and IIA would not be detected lo In patients with group II, dilatation and plethora of arterioles, capillaries, and venules were observed with varying degrees of severity. The number of arterio-venous anastomoses was increased. In some vessels of the microvasculature, accumulation of protein masses was noted. In patients with group III, dilatation of arterioles, capillaries, and venules was also diagnosed with varying degrees of severity. In patients with MM, complicated by CRF, in the vessels of the microvasculature, the accumulation of protein masses was more pronounced than in patients of group II. This can be explained by increased lung function in conditions of azotemic uremia .

In order to study microhemocirculation in the proximal parts of the bronchial tree, 30 patients with MM underwent endobronchal LDF (10 patients from group I, 10 from II and 10 from group III). The results were compared with the data of 20 people from the control group, who were conducted PBS and LDF. In patients with MM in the course of tumor progression, disturbances of microcirculatory blood circulation in the bronchial mucosa were recorded in terms of the nature and severity of the microcirculatory circulation.

The indicator of the microcirculation parameter (PM), which characterizes the state of tissue perfusion, was significantly reduced as MM progressed. In multiple myeloma, impaired microhemocirculation in the lungs and bronchi is primarily due to the syndrome of increased blood viscosity and anemia. In order to minimize the effect of anemia on the PM indicators, in patients with MM groups II and III, the anemic syndrome was stopped before the study. The hemoglobin level during LDF was not lower than 100 g / l, the content of erythrocytes was not lower than 3 × 10 9 / l. Thus, they tried to establish a decrease in the speed of red blood cells in the microvessels, which, in MM, is primarily due to the syndrome of increased blood viscosity. A significant inverse correlation was established between an increase in the serum paraprotein level and a decrease in PM (r = –0.8, P <0.01), between the duration of the disease MM and a decrease in PM (r = –0.64, P <0.05). ), between an increase in the level of creatinine in the blood and a decrease in the PM (r = –0.5, P <0.05).

The values ​​of the mean square deviation of PM (σ), reflecting the preservation of the mechanisms of blood flow regulation in the microcirculatory bed, in patients of groups I and II did not have significant differences compared with the control (P> 0.05), and decreased in group III ( P <0.001) . The coefficient of variation (Kv), which characterizes the dependence of tissue perfusion on blood flow modulation, increased during tumor progression and in all groups significantly exceeded control (P <0.001) .

When analyzing the rhythmic components of blood flow oscillations, a decrease in e-range fluctuations was observed in patients of groups II and III. In group I patients, the amplitude of oscillations in the E-band did not differ from the control indices (Table 30). A decrease in the amplitude of oscillations in the E-band indicates endothelial dysfunction and a decrease in the production of nitric oxide in MM patients in the later stages of the tumor progression. The decrease in endothelial oscillations correlated with the stage of the disease (r = –0.72, P <0.01), the level of paraprotein (r = –0.56, P <0.05) and blood creatinine (r = –0.56 P <0.05). Since in patients with another lymphoproliferative disease – CLL, there are no changes in endothelial oscillations, it can be assumed that, in MM, important factors for the development of endothelial dysfunction are paraproteinmia,dysproteinemia and uremic intoxication. Endothelial dysfunction of the microvasculature vessels contributes to a severe and prolonged course of inflammatory processes of the bronchopulmonary system in patients with MM and an increase in pressure in the pulmonary artery system.

In patients with MM, no significant changes in the oscillations in the H-, M-, D- bands were detected. The amplitudes of oscillations in the C-band in patients with MM decreased in the course of tumor progression; in group I, they did not have significant differences compared to control; in groups II and III, the indices of cardiac waves decreased significantly (P <0.05 and P <0.001, respectively). A decrease in cardiac wave values ​​indicates a decrease in arterial blood flow into the microvasculature due to the development of a syndrome of increased blood viscosity. According to the data of endobronchial biopsy, in patients of the third group, protein stasis is more pronounced than in patients of the second group; therefore, in the presence of renal insufficiency, the smallest indicators of vibration amplitudes in the C-band were recorded.Significant inverse correlations were found between the level of serum paraprotein of the blood and a decrease in fluctuations in the C-range (r = –0.7, P <0.01), between the duration of MM disease and a decrease in the fluctuations in the C-range r = – 0.58, P <0.05), between the level of blood creatinine and the decrease in fluctuations in the C-band (r = –0.5, P <0.05).

It is obvious that similar violations of microhemocirculation occur in the lungs. Thus, in a significant number of patients with MM II and III groups, during radiological methods of examination, there is an increase and deformation of the pulmonary pattern, which is caused by stagnation of blood in small vessels with the development of pneumosclerosis, since due to the increased viscosity of the plasma, blood flow slows down pulmonary capillary system.

Disruption of microhemocirculation contributes to the violation of tissue trophism, the development of tissue hypoxia, metabolic disorders in the cells of the bronchial mucosa. The consequence of this are atrophic changes in the bronchial mucosa. In 40% of MM patients, bilateral diffuse atrophic endoscopy develops. At the same time, in patients with MM, in contrast to patients with CLL, outside the attachment of AML, in no case was a latent inflammatory process occurring in the bronchial mucosa, despite the fact that CLL also shows markedly abnormal microhemomas in the process of tumor progression. – circulation. This can be explained by a more pronounced decrease in cellular and humoral immunity in patients with CLL compared with patients with MM . In patients with CLL, due to the deep mismatch of all parts of the cellular and humoral immunity, against the background of a violation of the trophism of the bronchial tissues, the inflammatory process quickly develops and then acquires a chronic course.

Disruption of microhemocirculation in the vessels of the lungs and bronchi, along with pronounced secondary immunodeficiency, lymphoid and plasma cell infiltration of the lung tissue, paraproteoinosis of the lungs, contribute to the occurrence of severe and prolonged pneumonia in patients with MM. So in patients with MM I group, where no microcirculation disorders were detected, pneumonia was not registered. In group II, pneumonia was diagnosed in 10 patients (18% of the total number of patients in this group), in group III in 23 patients (42%).

The effect of cytostatic therapy on microhemocirculation indices in patients with MM was studied. In cases where, after carrying out cytostatic treatment, it was possible to reach the phase of a stable “plateau”, a decrease in blood paraprotein was noted, endobronchial LDF was repeated for MM patients. In all, an increase in the PM indices was noted, but in no case did the PM indices completely normalize. An improvement in the amplitudes of oscillations in the endothelial and cardiac ranges was noted. (Table 31).

The persistence of endobronchial microhemocirculation disorders in patients with MM, after reaching the “stable plateau” phase, is explained by the multifactorial nature of the microcirculatory disorders. In addition to the syndrome of increased blood viscosity and anemia, impaired platelet and plasma hemostasis, vascular endothelium, regulation of tissue vascular tone, pH and pO 2 , hormonal background and many other factors affect the microcirculation . In the majority of patients with MM, the plateau phase maintains a minimum PIg production.

As in CLL patients with MM, a high degree of effectiveness of the endobronchial LDF method was noted for identifying vascular and intravascular disorders of the microvasculature of the mucous bronchi in the early stages of the pathological process. The role of LDF in the diagnosis of endothelial dysfunction of microvasculature vessels is very important . The use of this method allows to assess the dynamics of microcirculatory disorders in the mucous membrane of the proximal bronchi during the treatment of myeloma.

According to the data of zonal rheography of the lung in patients of the I group, there were no violations of the general and regional ventilation of the lungs, the vertical gradient of ventilation characteristic of healthy people remained unchanged . The ratio of MOVR of the upper zones / MOVR of the lower zones did not have significant differences compared with the control . No significant impairment of the pulsatory blood flow in this group was also detected. The regional VPO indicators and the total VPO indicator of both lungs did not differ from the control indicators.

Note: P 1 – the significance of differences compared with the control; P 2 – the significance of the difference between the indices of LDF, before and after achieving remission.

In patients with MM of group II, during reopulmonography, there is a decrease in general and regional ventilation of the lungs . A significant decrease in ventilation in the middle and lower zones of both lungs, a decrease in the total MOBP from all zones of the lungs by 29.4% (P <0.05) and redistribution of ventilation from the lower and middle to the upper zones of both lungs were diagnosed . A decrease in the rheographic index of systolic blood filling (SCR) and the index of minute pulsatory blood flow (MPCr) in the right lung was diagnosed. The mccr of the right lung is reduced, compared with the control, with a reliability of <0.05. In the left lung, a significant decrease in blood flow occurred only in the middle zone. The cumulative index of MCR had no significant difference with the control (P> 0.05) . A significant increase in vascular resistance was noted in the lower and middle (to a lesser extent) zones of both lungs, which can be judged by the decrease in HSC and in the length of the Q-interval . But there was no significant redistribution of pulmonary blood flow in patients of group II. Estimating the state of the venous outflow in the small circle of blood circulation due to DSC change, an increase in this index was found in the middle and lower zones, with the greatest values ​​of the coefficient in the basal regions of the lungs. Significantly reduced VPO upper and lower zones and the left lung as a whole (P <0.001). Despite the fact that in the right lung the integral indicator of HPE did not have significant differences with the control, the total index of HPE of both lungs was reduced .