[Prognostic value of a number of blood laboratory parameters in the use of erythropoiesis-stimulating agents in anemic patients with lymphoproliferative diseases].

AIM: To clarify the prognostic value of the baseline blood levels of endogenous erythropoietin (EE) and tumor necrosis factor-a (TNF-a) involved in the key components of the pathogenesis of anemia in lymphoproliferative diseases (LPD), the counts of reticulocytes and platelets (hematopoietic preservation indicators) in the use of erythropoiesis-stimulating agents (ESAs) to correct anemia syndrome (AS) in patients with LPD. SUBJECTS AND METHODS: The results of AS treatment with ESAs were analyzed in 48 patients with LPD. A study group comprised patients with chronic lymphocytic leukemia (n=1 3), indolent lymphomas (n=14), and multiple myeloma (n=21). Their hemograms (hemoglobin concentration, red blood cells, packed cell volume, reticulocytes, and platelets) and blood EE and TNF-alpha levels were examined before using ESAs. The hemogram was monitored during treatment. ESAs (eralfon (epoietin alpha) in 21 patients and epres in 27) were subcutaneously injected in a dose of 150 IU/kg thrice weekly (for not more than 16 weeks). A control group included 21 anemic patients with multiple myeloma who did not receive ESAs. Increasing hemoglobin concentrations up to 120 g/l was regarded as a positive response to ESA treatment. RESULTS: By and large, the efficacy of epoietin alpha was 62.5% (61.9% for eralfon and 63.0% for epres), which was significantly higher than that in the control group (23.4%; p<0.05). A number of blood laboratory parameters were found to be of value in predicting the efficacy of ESAs. The patients with the decreased baseline concentrations o EE ( <130 mlU/ml) and TNF- alfa (,15 pg/ml) were ascertained to show a positive response more frequently (80 and 92.9%, respectively; p<0.05) than those with thepredicting the efficacy of ESAs. The patients with the decreased baseline concentrations of EE (<130 mlU/ml) and TNF-a (<15 elevated concentrations of the enzymes in question. In addition, a positive response was more often recorded in patients with reticulocyte counts of more than 1% (77.4%; p<0.05) and platelets of 100-10(9)/1 (70%; p=0.05). CONCLUSION: Estimating the baseline blood levels of EE and TNF-a and the counts of reticulocytes and platelets prior to the use of ESAs enables prediction of the efficiency of erythropoiesis-stimulating therapy in anemic patients with LPD.

[The use of biochips for immunomorphological diagnosis of chronic lymphocytic leukemia].

Immunological biochips (immunobiochips) based on antibodies--test-systems, allowing simultaneously to determine an existence of different antigens in the material. Biochip of this class is usually a plate (substrate), on which antibody molecules with known specificity are immobilized within well-defined areas. The advantage of the use of biochips is the ability to define a large number of antigens at very low flow rates of antibodies. Biochips can be used for many tasks, including immunophenotyping for tumor cells. There are presented the results of testing of biochips made in laboratory conditions to determine surface antigens of cells in patients with chronic lymphocytic leukemia. It is showed a good agreement between the results of immunophenotyping of cells in chronic lymphocytic leukemia patients with the use of biochips with data of flow cytometry.

[The combination of chronic myeloid leukemia and multiple myeloma in one patient].

The article describes the clinical observation of a patient with simultaneous course of lymphoid and myeloid neoplasms. The patient developed two diseases--chronic myeloid leukemia (CML) and multiple myeloma (MM), which were confirmed by corroborated hemogram, myelogram, immunophenotyping of bone marrow cells, biopsy, immunohistochemical, cytogenetic, biochemical and radiological studies. Target therapy of CML with tyrosine kinase inhibitors (imatinib at the standard dose of 400 mg per day) has provided a complete cytogenetic remission at 6 months and major molecular response at 18 months of treatment. Administration of 2 courses of programmed treatment "BD" > (bortezomib + dexamethasone) resulted in a very good partial response, which was maintained through a year and a half. However, against the background of programmed treatment there were developed complications as polyneuropathy of grade 2, which was treated with thioctacide, milgamy, and anemia of grade 2, successfully treated with epoetin beta. Subsequently, the patient was administered continuously with imatinib 400 mg that kept the major molecular response. Relapsed MM was revealed in 20 months and confirmed by a full clinical and hematological examination. The absence of organ dysfunction allowed choosing a supervisory tactics for the patient.

[Molecular biology investigation of respiratory viruses as a factor of infectious complications in hemoblastosis and myelodepression].

Communicable respiratory viruses as a causative factor of infectious complication in hemoblastosis and myelodepression were investigated in 51 patients (aplastic anemia--3, multiple myeloma--10, different patterns of acute leukemia--16, chronic leukemia--8 and non-Hodgkin's lymphoma--14). Our clinical evidence obtained with the aid of polymerase chain reaction featured genomes of adenoviruses, influenza A and B viruses, respiratory-scintillating virus and coronaviruses. On the whole, respiratory viral infections were detected in 27 (52.9%) patients: adenoviruses--23.5%, coronaviruses--13.7%, influenza A and B--5.9% and respiratory-scintillating virus--3.9%. In many cases, herpes was associated with viral respiratory infection. That pathology was most often triggered by severe neutropenia induced by chemotherapy.

[The colony-forming capacity of the precursor cells of granulomonocytopoesis in bone marrow aplasia]. / Kolonieobrazuiushchaia sposobnost' kletok-predshestvennikov granulomonotsitopoéza v usloviiakh aplazii kostnogo mozga.

Retrospective analysis of 80 patients with aplastic anaemia (AA) was performed in order to examine clonogenic properties of granulomonocytopoiesis precursors and to specify the extent of disorder of hemopoiesis in AA. Sharp decrease of clonogenic properties of precursors, especially in severe form of AA was established to be present in 95% of patients, while only in 5% of patients initial indexes of the clonogenic ability were discovered to be normal. After treatment with ALG, prednisolum and androgen and also after splenectomy, clonogenic ability increased appropriately in 43%, 16.6% and 76.9% of patients, although the effect was not steady. The best results were obtained after allogenic transplantation of bone marrow (TBM), when the clonogenic properties normalization was observed against the background of remission 1-3 years lasted. Thus, low indexes of clonogenic properties of the precursors of granulomonocytopoiesis in AA, and positive effect of TBM may indicate the lesion of the precursor. At the same time normal initial indexes in some patients, and diverse effect of different methods of therapy make it possible to admit the probability of the lesion of stromal microenvironment cells.

[Morphological and pathogenetic aspects of aplastic anemia]. / Morfologicheskie i patogeneticheskie aspekty aplasticheskoi anemii.

A complex study of colony-stimulating properties of cells-precursors of granulomonocytopoiesis, morphological parameters of the marrow histological structures and immunological parameters was carried out in 90 patients to specify pathogenic mechanisms of aplastic anemia (AA) development. 95% of patients appeared to have sharp decrease of the marrow colony-stimulating properties and only 5% had normal initial indexes. In most patients endostal cell number increased, while the content of reticulocytes grew higher in more than 30% of patients. Defect of the marrow stroma functioning was registered in 23% of patients. Increase of the osseous tissue volume and osteocyte number was found. Dysbalance in cellular link of immunity was demonstrated. Only temporal increase of the marrow colony-stimulating properties was marked in some patients on the background of treatment with antilymphocyte globulin, despite the clinic-hematological improvement. Multifactor pathophysiological mechanisms, the main of which is the stem cell defect lies in the base of AA pathogenesis. Hemopoietic microenvironment pathology is not the leading reason of the hemopoiesis depression but it contributes greatly in its development. Immunological alterations in patients with AA are secondary and can be partly corrected with treatment with ALG.

[Morphofunctional characteristics of stromal structures of bone marrow in aplastic anemia patients]. / Morfofunktsional'naia kharakteristika stromal'nykh struktur kostnogo mozga u bol'nykh aplasticheskoi anemiei.

Stromal structures of the bone marrow in 22 patients with aplastic anemia (AA) were studied histophotometrically. A significant increase of the fat tissue volume and a decrease of hematopoietic tissue volume were observed. Bone tissue volume was significantly increased in 81.8% of patients, the number of endosteal cells was increased in all the patients and that of reticular cells in one third of them. The conclusion is made that hematopoietic microenvironment of the bone is not a determining factor in the majority of AA patients. Excessive bone formation might be one of the mechanisms of aplasia development.

[Kidney involvement in idiopathic myelofibrosis]. / Porazhenie pochek pri idiopaticheskom mielofibroze.

Functional potential of the kidneys, principal causes of nephrolithiasis and chronic renal failure were investigated in 30 idiopathic myelofibrosis (IMF) patients by combination of different modalities, sonography, in particular. Sonography proved highly informative in diagnosis of nephroliths the formation of which is attributed to derangement of uric acid metabolism, of renal elimination, and anatomical features of the urinary system. A correlation analysis between various factors showed that in IMF hyperuricemia, hyperfiltration and proteinuria damage cortical and medullary layers of the kidneys provoking their functional defects and development of chronic renal failure.

[The use of the preparation bonefos in the combined therapy of multiple myeloma patients]. / Primenenie preparata bonefos v kompleksnoi terapii bol'nykh mnozhestvennoi mielomoi.

A clinical trial of a new drug bonefos (Leiras, Finland) in 13 patients with multiple myeloma confirmed its potent analgetic effect. Alleviation of ostealgia was seen as early as the treatment day 5-7. The drug inhibits the progression of skeletal tumor growth, reduces the frequency of bone fractures, normalizes calcium concentrations in the blood and urine. Side effects such as nausea and short-term epigastric pains occurred in 23% and 15.38% of the patients, respectively.

[The polychemotherapy of patients with multiple myeloma]. / Polikhimioterapiia bol'nykh mnozhestvennoi mielomoi.

The paper deals with the analysis of the results of chemotherapy of 78 patients with multiple myeloma using various combinations of cytotoxic drugs such as vincristine, cyclophosphamide, sarcolysine (melphalan), rubomycin (adriamycin) and prednisolone (dexamethasone). Reaferon was added in some cases. Response was evaluated according to standard criteria. Survival and response were assessed versus treatment modality and immunochemical type of disease. The most effective chemotherapeutic regimens for multiple myeloma are discussed. It is recommended that remission induction be followed by courses of consolidation treatment and then by maintenance therapy. Reaferon used as a component of complex treatment for multiple myeloma was shown to markedly potentiate the antitumor effect.

[The basic mechanisms of the development of kidney failure and the methods for its correction in multiple myeloma]. / Osnovnye mekhanizmy razvitiia pochechnoi nedostatochnosti i metody ee korrektsii pri mnozhestvennoi mielome.

To examine functional capacities of the kidneys, reserve potentialities of the urinary tract and the mechanism of the development of chronic renal failure (CRF) in multiple myeloma (MM), 60 patients were examined. In addition to the routine methods of examination, all the patients were subjected to renal sonography. It has been shown that the main causes of CRF in MM are proteinemia and paraproteinuria. Emphasis is laid on the importance of sonography that enables one to measure not only the size of the kidneys, to estimate the status of the parenchyma and calyceal system, but also to reveal the derangement of urodynamics of the upper urinary tract in the stage of latent CRF. It has been demonstrated that one of the effective methods of removing CRF lies in therapeutic plasmapheresis, which is advisable in MM patients even in latent renal failure, preventing the impairment of the tubular system and increasing the filtration and reabsorption capacity of the kidneys.

[Changes in myocardial function in patients with acute leukemias under the influence of rubomycin]. / Izmeneniia funktsii miokarda u bol'nykh ostrymi leikozami pod vliianiem rubomitsina.

Physical electro- and echocardiographic methods were used to study myocardial function in 70 patients with acute leukemia (AL). 40% of them in the primary active phase had hypokinetic, while 60% hyperkinetic circulation. Leucocytosis and thrombocytopenia proved prognostically unfavorable for myocardium condition. Cardiotoxic rubomycin doses have been established. Pathogenic mechanisms underlying deterioration of myocardial contractility, reduction of stroke volume and rearrangement of central hemodynamics are considered. Administration of riboxin with finoptine promoted normalization of clinical and improvement of echo-CG sings of myocardiopathy in patients given total rubomycin doses 200-450 mg/m2.

[Alpha-2a-interferon (Reaferon) in the treatment of patients with multiple myeloma]. / Al'fa-2a-interferon (Reaferon) v lechenii bol'nykh mnozhestvennoi mielomoi.

Sixty-six patients with multiple myeloma were divided into four groups: treatment with alpha-2a-interferon (reaferon) 3-5 mln MU/m2 alone (group); alpha-interferon + pulsed therapy with dexamethasone (group II); reaferon at high or low dose + different regemens of polychemotherapy (group III), and polychemotherapy followed by therapeutic support with melfalan and prednisone (MP) (control). Patients in group I untreated earlier with MP showed positive response in 80% while only 20% were in partial remission. Chemoresistance was broken in 86% (complete clinico-hematological remission--18%) following administration of high doses of alpha-interferon in conjunction with cytostatics. Reaferon + dexamethasone modality proved less effective. After chemoresistance was broken in 83%, tumor process reached a plateau. Low-dose reaferon was less effective, too, with complete remission never being reported. When administered in high doses as support therapy, it proved fairly effective, with median response being double that registered at low dosage or chemotherapy + MP. Whenever high-dose alpha-interferon tolerability is poor, dosage can be decreased; the patients may continue on low dosage or switch to MP support.

[The importance of sonography in the diagnosis of extramedullary hematopoietic foci in acute leukemia]. / Znachenie sonografii v diagnostike ékstramedulliarnykh ochagov krovetvoreniia pri ostrom leikoze.

Ultrasonographic examination of the abdominal cavity and retroperitoneal space was performed in 102 patients with acute leukemia (AL) of whom 70 suffered acute non-lymphoblastic leukemia (ANLL) while the other 32--acute lymphoblastic leukemia (ALL). All the patients were divided into 3 groups: primary-active disease, complete clinical and hematological remission and patients in relapse. Group 1 revealed hepato- and splenomegaly as well as changes in the ultrasonographic structure of these organs, whatever type of leukemia. Half the ANLL patients had tumor in the abdominal cavity, and splenic changes were more apparent in them. Ultrasonography was shown to be instrumental in evaluating clinical and hematological response, timely diagnosis of slightest hepato- and splenomegaly and detection of changes in the structure of the organs as well as abdominal lymph node hyperplasia. Echography should be also recommended for monitoring the course of leukemia, response and morphologic and functional status of the viscera throughout the disease. Ultrasonography should find wide application in leukemia studies to increase our knowledge of the disease.

[The diagnostic importance of echography of the spleen, abdominal lymph nodes and vessels in chronic lympho- and myeloleukemias]. / Diagnosticheskoe znachenie ékhografii selezenki, abdominal'nykh limfouzlov i sosuodov pri khronicheskom limfo- i mieloleikoze.

Echography of the spleen and abdominal vessels was performed in patients with chronic myeloleukemia (CML) and chronic lympholeukemia (CLL). The patients belonging to these groups manifested enlargement of the spleen, alterations of its echo structure and dilatation of the vessels even at the initial disease stage. Appreciable splenomegaly with a proportional increase of the diameter of the main vessels of the abdominal cavity and derangement of the splenic echo structure were ascertained in patients in the stage of pronounced clinicohematological manifestations. Moreover, provided those diseases run an atypical course, echography of the spleen, abdominal lymph nodes and vessels is of differential diagnostic importance. As compared to patients with CLL, the spleen of those with CML differed as regards the extent of enlargement and alterations in the organ structure in different stages of the tumorous process. There were differences in the diameter of the abdominal vessels. The patients with CML demonstrated splenic infarctions of different standing whereas patients with CLL conglomerates of the abdominal lymph nodes. In patients with CML, remarkable splenomegaly was observed more frequently. Echography of the spleen and vessels in patients with CML and CLL is a highly informative, noninvasive and safe method which is likely to be widely used in hematology.

[The echographic and biochemical signs of liver and splenic involvement in patients with aplastic anemia]. / Ekhograficheskie i nekotorye biokhimicheskie priznaki porazheniia pecheni i selezenki u bol'nykh aplasticheskoi anemiei.

Sonography of the liver, gallbladder, portal and splenic veins, biochemical hepatic tests were conducted in 35 patients with aplastic anemia (AA). The patients were ill from 3 months to 20 years. Depending on AA, duration some patients displayed a small enlargement of the liver, changes in its echo structure, increased calibre of the portal veins. Moderate hepatomegaly was associated with biochemical shifts reflecting dysfunction of hepatic tissue. The above sonographic and biochemical changes observed usually in toxic hepatitis result from different chemical compounds produced within AA genesis, from administration of anabolic hormones and other drugs, frequent transfusion of red cells and other blood components. The size of the spleen was not changed, though its echo pattern was abnormal.

[The necessity for the combined use of the ultrasonic study of the abdominal cavity organs and of the histomorphometry of the bone marrow in chronic myeloleukemia]. / O neobkhodimosti sochetannogo ispol'zovaniia ul'trazvukovogo issledovaniia organov briushnoi polosti i gistomorfometrii kostnogo mozga pri khronicheskom mieloleikoze.

Forty-one patients with chronic myeloid leukemia (CML) were divided into 3 groups: 13 patients in a chronic phase prior to cytostatic treatment group 1; 17 patients in a chronic phase treated with myelosan group 2; 11 patients in a blast transformation phase group 3. All of them underwent abdominal sonography in line with marrow histomorphometry. Ultrasound investigation is thought indispensable in examination of CML patients as it registers negligible enlargement of the liver and spleen and provided their echo structure. It makes possible to trace stages of the tumor process development. CML involves in the pathological process the kidneys as shown by changes in the echo pattern, concrements are often formed in the pelvicalyceal system. Group 1 patients demonstrated reduced area of the bone tissue by morphometrical evaluation of the bone marrow. This means prevalence of osteolysis in CML onset. In group 3 patients this value is higher indicating osteosclerosis predominance. Comparison of the ultrasonic and histomorphometric data suggest that enlargement of the spleen and liver with diffuse vegetations of the connective tissue and their fibrotic lesion of the parenchyma correlated with the severity dissemination of hemopoietic tissue collagen fibrosis. It is evident that CML is characterized by fibrosis involving simultaneously bone marrow, splenic and hepatic parenchyma.

[Immunological and rheological disorders in multiple myeloma patients]. / Immunologicheskie i reologicheskie narusheniia u bol'nykh mnozhestvennoi mielomoi.

Overall 30 patients with multiple myeloma (MM) were examined for immunological and rheological parameters. MM was shown to be marked by imbalance of immunobiological reactivity, with the greatest changes being seen in the B cell immunity system. MM is also characterized by marked rheological shifts related to the immunological alterations and underlying the hyperviscosity syndrome and heart failure. Administration of polychemotherapy resulted in a decrease of the count of B lymphocytes, circulating immune complexes; a tendency toward normalization of the rheological blood properties was observed. Introduction of plasmapheresis into the treatment program of the patients noticeably raised the treatment efficacy.

[The effect of different programs of cytostatic therapy on the blood coagulation and rheological properties in multiple myeloma patients]. / Vliianie razlichnykh programm tsitostaticheskoi terapii na gemokoaguliatsionnye i reologicheskie svoistva krovi u bol'nykh mnozhestvennoi mielomoi.

Three different programs of polychemotherapy (PCT) of multiple myeloma (MM) were compared. The programs included the use of cyclophosphamide (up to 750 mg/m2), vincristine (1.4 mg/m2), rubomycin (40 mg/m2), sarcolysine (7.5 mg/m2), paphencyl (50 mg/day) and prednisolone (from 30 to 60 mg/m2) in different combinations with regard to the hemocoagulation and rheological blood properties. It has been shown that in patients with MM there occur profound hemocoagulation and rheological alterations playing an important part in the genesis of the syndrome of hyperviscosity and circulation failure. The use of the programs of PCT in conjunction with therapeutic plasmapheresis brought about an appreciable improvement of the patients' general health status and correction of hemocoagulation and hemorheological disorders. To control the efficacy of PCT, its individualization, intensity and duration, it is recommended that in addition to the common tests, the activity of the antithrombin-III-heparin complex may be measured and the test for the presence of fibrin monomer in the plasma be made, since these parameters clearly reflect the changes in the system of hemostasis and enable one to discover the early signs of proliferation activation in MM thereby preventing hemorrhages.

[Platelet glycosaminoglycans in paraproteinemic hemoblastoses]. / Glikozaminoglikany trombotsitov pri paraproteinemicheskikh gemoblastozakh.

The content and composition of platelet glycosaminoglycans (GAG) were studied in 24 patients with paraproteinemic hemoblastoses (22 patients with myelomic disease and 2 with Waldenstrom's disease). According to the GAG levels, the patients were divided into 2 groups: 1) 6 patients with its higher levels (181 +/- 8 micrograms of uronic acids per 100 mg of acetone-dried cells) and 2) 18 patients with its close-to-normal levels (129 +/- 4 micrograms per 100 mg of the cells). Marked manifestations of hemorrhagic diathesis were found in 5 patients in Group 1 and in 1 in Group 2. Chondroitin sulfate was demonstrated to prevalent in the platelets of patients with paraproteinemic hemoblastoses, as in those of healthy persons. There was GAG electrophoretic profile depletion due to the reduced number of minor components of non- and low-sulfated GAG in 14 patients. It is suggested that the changes detected in the content and composition of GAG may contribute to platelet dysfunction in these diseases.