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Biomedical subjects

V G Savchenko

Publications and source records attributed to V G Savchenko.

At least 19 recordsLinked to original sources
PubMed2006

Genetic differences by platelet-specific antigens used for monitoring allomyelotransplant engraftment.

Monitoring of allomyelotransplant engraftment is essential for evaluation of the function of transplanted cells and timely diagnosis of disease relapse. The possibility of using differences by HPA genes for monitoring of survival of transplanted hemopoietic stem cells was studied. Differences by HPA genes in HLA-identical sibs can be used for the analysis of chimerism after myelotransplantation.

Alleles↗
PubMed2006

[Efficacy and safety of transfusion therapy in hematological patients].

AIM: To determine whether probability of hepatitis B and C virus (HBV/HCV) infection of hematological patients depends on intensity of hemotransfusion therapy and to propose possible ways to diminish posttransfusion risk of virus infection with HBV/HCV. MATERIAL AND METHODS; A clinicoepidemiological prospective trial was made to monitor risk factors and indicators of HBV and HCV infection in 216 patients of a hematological department of the Hematological Research Center. A total of 447 hospitalizations (229 rehospitalizations among them) to the department of chemotherapy, depression of hemopoiesis and bone marrow transplantation for 2 years were analysed. Statistics were analysed using SAS computer programs and the "landmark method". RESULTS: Transfusions of blood components before initiation of the trial were performed in 201 (93%) patients, 120 (60%) patients received more than one transfusion (median of the number of donors was 40). Markers of virus hepatitis were initially detected 1 month after hospitalization in 103 (47.7%) patients: HCV--in 26 (12%), HBV--in 77 (35.6%); 18 (17.5%) patients were coinfected (HBV/ HCV). Probability of detection of HBV and HCV markers in patients with multiple transfusions was significantly higher than in patients with a short transfusion history (50% probability of HBV and HCV infection was 153 and 251 days, respectively, p = 0.059). CONCLUSION: Reduction of aftertreatment lethality and, finally, treatment efficacy in hematological patients depends on adequacy of replacement therapy with blood components, platelets first of all. High percentage of HBV and HCV infection confirms dependence of infection probability on the number of donors. Thus, patients with planned massive replacement therapy should be provided with specially selected donors. Blood for transfusion for them should be examined for viruses repeatedly.

Biomarkers↗
PubMed2006

[Characteristics of T-cell immunity in patients with acute leukemia].

AIM: To study a cytokine profile of cytotoxic T-cells and T-helpers at diagnosis of acute myeloid and lymphoblastic leukemia (AML and ALL) and at different stages of its treatment. MATERIAL AND METHODS: T-cell population of peripheral blood lymphocytes was studied in 19 AML patients at diagnosis, 13 AML patients in remission, 5 AML patients in developing recurrence and 5 ALL patients at diagnosis. The control group consisted of 10 healthy donors. A mononuclear fraction of peripheral blood cells was stained with monoclonal antibodies. Surface expression of CD3, CD4, CD8 antigens was estimated with the use of flow cytofluorimeter FACS Calibur. Part of the cells were cultured for production of activated lymphocytes. The cytokine profile of T-cells was investigated according to the modified method of Rostaing et al. in the population of CD3+CD8+ and CD3+CD8- T-cells using the flow cytofluorimeter FACS Calibur. The results were processed with the programs CellQuest and WinMDI, Statistica Module Switcher. RESULTS: The percentage of CD3+CD8+ cells producing interferon-gamma (IF-g) was the same in AML patients and donors. The percentage of CD3+CD8- cells (T-helpers) producing IF-g was similar in the patients at diagnosis and in complete remission being higher than in healthy donors. The number of CD3+CD8- cells producing IF-g was reduced in recurrence while the number of CD3+CD8+ and CD3+CD8- cells producing interleukin-4 (IL-4) increased. In the onset of the disease, ALL patients had significantly increased percentage of CD3+CD8- IL-4 cells. CONCLUSION: The results obtained evidence for different polarization of T-cell immunity in AML and ALL patients at the time of diagnosis, remission and recurrence: in the onset of AML there was an increase in the production of Th1--proinflammatory cytokines, in ALL--in percent of Th-2 cytokines. In AML recurrence the balance of cytokines shifted in the direction of Th-2 response.

Acute Disease↗
PubMed2006

[Monitoring of minimal residual disease in patients with acute promyelocytic leukemia].

AIM: To study efficacy of different programs of maintenance therapy, to create the program of differential therapy of minimal residual disease (MRD) and molecular recurrences at all stages of acute promyelocytic leukemia (APL) basing on the results of monitoring. MATERIAL AND METHODS: A total of 76 APL patients entered the trial. They received therapy by the protocols APL-97/98, APL-01, AIDA, 5D. Expression of chymeric oncogen PML/RARa in the disease onset was estimated by bone marrow and/or peripheral blood examination with RT-PCR. The study of chymeric oncogen PML/RARa was made once in two months. RESULTS: The program of differential therapy of APL is proposed on the basis of molecular-biological monitoring of expression of chymeric oncogen PML/RARa. The results of molecular monitoring of MRD correlated with development of molecular and hematological recurrences. Therapeutic policy is determined after diagnosis of molecular recurrence. Further therapy of APL is determined which allows a rise in overall and recurrence-free survival of the patients. CONCLUSION: The efficacy of maintenance therapy only with cytostatic drugs or their combination with ATRA is similar. The response to biological therapy with ATRA plus interferon-alpha is not sufficient. Molecular recurrences--probable or documented--are detected in maintenance therapy 2 months earlier, on the average, than hematological ones. Changes in the treatment policy in registration of molecular recurrence significantly diminish probability of hematological recurrence (from 36 to 0%, p = 0.001.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

[Clonal chromosomal aberrations in patients with aplastic anemia at the disease onset and transformation].

AIM: To estimate detectability and characteristic features of chromosomal aberrations in bone marrow cells of patients with aplastic anemia (AA). MATERIAL AND METHODS: The trial covered 155 AA patients admitted to the Hematological Research Center in 1987-2002. Cytogenetic study by G-differential staining was performed in 58 patients with AA and 5 patients with AA transforming into myelodysplastic syndrome (MDS) or acute leukemia (AL). Cytogenetic and morphological specimens of the latter's bone marrow were studied retrospectively using fluorescent in situ hybridization (FISH) with DNA probes for detection of monosomia 7 and deletion 7q. RESULTS: Clonal chromosomal aberrations were detected in 4 out of 28 patients. Further examinations revealed no aberrations. Clonal diseases developed in 7 (4.5%) of 155 patients. In 2 patients the disease transformed into paroxysmal nocturnal hemoglobinuria, 5 (3.2%) patients developed variants of MDS and AL. Monosomia 7 or deletion 7q were diagnosed in 3 cases of MDS/AL. In retrospective study of bone marrow specimens of patients with transformation in MDS/AL with monosomia 7, FISH recognized a small elevation over control values in 2 cases. CONCLUSION: Stable clonal chromosomal aberrations are not characteristic of AA. Some AA patients with subsequent MDS/AL may have minor neoplastic clone in the disease onset.

Adolescent↗
PubMed2006

[Effect of cytarabine on expression of cell adhesion molecules and on endothelium-leukocyte interaction in vitro].

AIM: To characterize cytarabine effects on human endothelium expression of cell adhesion molecules (CAM) of various classes and interaction of cultured endothelial cells (EC) with blood leukocytes. MATERIAL AND METHODS: Primary cultures of EC of human umbilical vein were obtained by EC culturing for 24-72 h with cytarabine (10 mcg/ml). They were investigated with phase-contrast microscopy, immunohistochemistry and flow cytometry. RESULTS: Cytarabine effects manifested with EC-induced expression of cell surface P- and E-selectines and VCAM-1; ICAM-1 expression rapidly enhanced, leukocyte adhesion to endothelium also activates. CONCLUSION: Cytarabine, as a pathogenetic factor, induces proinflammatory alterations of the endothelium responsible for development of vascular complications in patients on cytostatic therapy.

Antimetabolites, Antineoplastic↗
PubMed2006

[Effect of parathyroid hormone (PTH 1-34) on hemopoiesis in long-term cultures of human bone marrow].

AIM: To study effects of parathyroid hormone (PTH) used in therapy of osteoporosis on hemopoiesis in long-term culture of human bone marrow (LCBM) in terms of its potential influence on stem hemopoietic and stromal cells. MATERIAL AND METHODS: For a long time LCBM was treated with PTH (1-34) and compared for cell production, concentration of late and early hemopoietic precursors. Maintenance of hemopoiesis and adhesion at early hemopoiesis precursors on the stromal sublayers treated with PTH (1-34) was used as a functional test. A relative level of expression of genes participating in regulating proliferation and self-support of stem hemopoietic cells was studied. RESULTS: PTH (1-34) in the above concentrations did not affect hemopoiesis in LCBM. Stromal sublayer treated with PTH (1-34) for a long time supports cell precursors better, their adhesion to such sublayers enhances. CONCLUSION: PTH (1-34) in pharmacological but small concentrations had no irreversible effects on hemopoiesis, i.e. contraindications for its use in the treatment of osteoporosis were not revealed.

Adult↗
PubMed2006

[Splenectomy in programmed therapy of aplastic anemia].

AIM: To define efficacy of splenectomy (SE) in current programmed therapy of aplastic anemia (AA). MATERIALS AND METHODS: SE efficacy was analysed in 2 stages: a retrospective study of efficacy of surgery as monotherapy (1986-1996) (74 AA patients) and of SE in programs of immunosuppressive therapy (IST) (1991-2002). Program treatment of AA patients was conducted on the base of IST algorithm developed in Hematological Research Center after many year investigations. RESULTS: SE as monotherapy improved AA course in 73.3% patients with non-severe AA (NAA) and 18.2% patients with severe AA (SAA). Three and five year survival in NAA postsplenectomy patients was 80%. One-year survivors after surgery were likely to survive long. Overall survival of SAA after SE was significantly less (p < 0.0001): 3-year survival - 6%. SE efficacy in programs including antilymphocytic globulin (ALG) and cyclosporin A (CsA) was studied in 69 AA patients. A 85.5% response was registered to program treatment including ALG, CsA and SE, being 81% in SAA and 1% in NAA patients. Efficacy of SE in combination with CsA at the first stage NAA treatment (a 30% positive response) was much inferior to ALG+CsA (68% response). At stage two treatment SE improved treatment results in most of SAA patients. Long-term survival in SAA patients after program treatment with SE is 60%. CONCLUSION: SE in the program of combined therapy in adult AA patients including CsA is an alternative to ALG in NAA patients. In SAA, SE can be included in the program at the first stage in ALG intolerance or in the absence of the drug, at the second stage--to overcome resistance to conducted therapy.

Adolescent↗
PubMed2005

[Acute lymphoblastic leukemias with aberrations of BCR-ABL genes].

AIM: To develop an original therapeutic strategy in Ph-positive acute lymphoblastic leukemia (ALL). MATERIAL AND METHODS: In November 2001 Hematological Research Center (HRC) initiated the study of chimeric BCR-ABL gene. During the first stage of the study (November 2001-July 2004), 18 primary ALL patients were recruited in HRC, from July 2004 to January 2005--16 patients in HRC, N.N. Burdenko Central Military Hospital, regional Samara hospital. The diagnosis of Ph-positive ALL was established in detection of translocation t(9;22) by standard cytogenetic test or fluorescent hibridization in situ with double signal (D-FISH), or by polymerase chain reaction with reverse transcription (RT-PCR). In detection of aberration of BCR-ABL gene the patients received stem hemopoietic cells, from June 2004 imatinib was added to chemotherapy in the period of induction and consolidation. RESULTS: Incidence rate of BCR-ABL-positive ALL by standard cytogenetic test and D-FISH makes up 20%, by RT-PCR--25%. Differences in chimeric transcripts detectability by different methods may be explained by different sensitivity of the methods. Complete hematological remissions were achieved in the majority of the patients (6 of 8) irrespective of imatinib administration. Achievement of molecular remission in BCR-ABL-positive ALL occurs also in standard chemotherapy but molecular remissions begin 2-4 months later than clinicohematological ones. CONCLUSION: In using imatinib combination with chemotherapy, molecular remission can be achieved simultaneously with hematological one. Long-term results will be analysed later.

Adolescent↗
PubMed2005

[Renal lesion in hemoblastoses].

AIM: To study morphofunctional condition of the kidneys in patients with hematological malignancies. MATERIAL AND METHODS: Renal function, i.e. concentration ability, glomerularfiltration rate (GFR), concentration of electrolytes and beta2-microglobulin in blood serum and urine was studied at different stages of chemotherapy. Three cases are reported. All the patients have undergone transcutaneous fine-needle puncture biopsy of the kidney with histological and electron-microscopic study of biopsy specimens. RESULTS: Total urinalysis showed minimal changes. Concentration and filtration functions of the kidneys were impaired. Morphologically, glomerular damage was insignificant, there was dystrophy of tubular epithelium and focal interstitial sclerosis. Electron-microscopic examination revealed structural defects of the basal membrane of glomerular capillaries (focal thinning, focal insignificant thickening, the absence of three-layer structure at long distance) in all the patients. Dissection of the basal membrane was seen in one case. All the patients had cytoplasmic viruses: Epstein-Barr, cytomegalovirus, herpes simplex viruses type 1 and 2. In two cases mitochondria were affected with viruses. Dystrophic changes of podocytes and mitochondrial degradation were observed in all the cases. CONCLUSION: Chemotherapy may affect glomerular and tubular system of the kidney increasing probability of complications. Imbalance between cytolysis kinetics and natural clearance of the products of degradation of cells and drug metabolites may lead to nephropathy. Viral infection indicates immunodeficiency due to immunosuppression or is a direct cause of impairment of renal endothelium cells. No definite recommendations can be made still about therapeutic policy.

Adult↗
PubMed2005

[Chromosomal aberrations in myelodysplastic syndrome].

AIM: To analyse incidence rate of chromosomal aberrations in myelodysplastic syndromes (MDS), specification of clinicomorphological features of some cytogenetic variants. MATERIAL AND METHODS: Chromosomal analysis by the method of G-differential staining of chromosomes was made in 209 patients with different variants of MDS. RESULTS; Clonal chromosomal aberrations occured in 60.8%. The following aberrations were found most frequently: deletion of the long arm of the chromosome 5 (del(5q)) - 34.6%, trisomy of chromosome 8 (14.1%), monosomy of chromosome 7 (13.4%), aberrations 3q21q26 (12.6%), aberrations of a long arm of X-chromosome (4.7%), the absence of Y-chromosome (3.1%). Complex aberrations of karyotype were found in 13.5% cases. Chromosomal aberrations determined not only clinical and morphological features but also the prognosis of the disease. CONCLUSION: Cytogenetic examination is an essential component of MDS patients examination. It allows more precise classification of MDS variant and prognostification of the disease course.

Adolescent↗
PubMed2005

[Infectious complications after transplantation of autologous hemopoietic blood cells in patients with hematological malignancies].

AIM: To characterize infectious complications arising within 30 days after transplantation of autologous hemopoietic blood cells in 42 patients with hematological malignancy (HM); to compare the course of early posttransplantation period with reference to a kind of high-dose conditioning and dose of transplanted CD34+ cells. MATERIAL AND METHODS: Autotransplantation (AT) was conducted as consolidation of a complete or partial remission in 20 patients with multiple myeloma, 14 patients with lymphogranulomatosis and lymphosarcoma, 7 patients with acute leukemia and 1 patient with rabdomyosarcoma. The program of pretransplantation conditioning corresponded to the disease form and included: melphalan, BEAM, busulphane-cyclophosphamide. The number of transplanted CD34+ cells was 1.7-20.1 (median 5.3) x l0(6) cell/kg. The transplantation was followed by selective intestinal decontamination and mycosis prophylaxis. Fever was managed with antibiotics. RESULTS: An early period after AT ran without febrile episodes in 7 (17%) patients. This allowed physicians to avoid systemic antibiotic therapy. The infectious focus was not definitely localized in 35 patients with febrile fever in 77% cases. Clinically and bacteriologically verified infections were detected in 8 (19%) patients: 7 cases of pneumonia and 1 of bacteriemia. None of the patients died of infection early after AT. Not a single case of invasive aspergillesis was registered. CONCLUSION: Incidence and features of infections did not vary with the above diseases and did not depend on the dose of transplanted CD34+ cells. The kind of high-dose conditioning had a significant influence on the time of granulocyte recovery, duration of agranulocytosis, duration of one febrile episode and of antibiotic therapy. The dose of transplanted CD34+ cells also influenced the time of granulocyte recovery and duration of antibiotic therapy.

Adult↗
PubMed2005

[Optimization of isolation of the concentrate of stem cells from the umbilical blood].

AIM: To study correlations between body mass and height of the newborn, Apgar scale estimates, gestation time, volume of the obtained umbilical blood (UB), number of nucleated cells (NC); to compare manual and automatic modes of UB processing. MATERIAL AND METHODS: 330 procurements of UB were made, 230 (69.7%) samples were frozen. Comparison of 2 techniques of UB processing was made in 73 cases of double centrifugation with hydroxyethylstarch (HES) and 47 cases of using separator Sepax (Biosafe, Switzerland). Blood cell count before and after UB processing and number of CD34+ cells were estimated. RESULTS: A correlation analysis was made of dependence of the volume of 102 samples of UB on the weight (r = 0.268, p < 0.01) and height of the fetus (r = 0.203, p < 0.05), estimation by Apgar scale (r = -0.092, p < 0.1) and gestation term (r = -0.003, p > 0.1); analysis of the number of NC dependence on the volume of UB (r = 0.102 p < 0.1), mass (r = 0.073 p > 0.1) and fetus height (r = 0.121 p > 0.1), gestation time (r = 0.159 p > 0.1), Apgar scale assessment (r = -0.174 p > 0.1). In manual UB management NC yield made up 71.9 +/- 6.7%, in automatic--81 +/- 8.0% (p < 0.05). Percent of erythrocytes removal was 73 +/- 5.7% and 80.5 +/- 6.1% (p < 0.05), respectively. CONCLUSION: A weak correlation was found between UB volume, mass and height of the fetus. The number of NC in UB depends on none of the parameters. Automatic processing of UB provides a greater release of NC and better elimination of erythrocytes in minimal risk of contamination.

Antigens, CD34↗
PubMed2005

[Invasive pulmonary aspergillesis].

AIM: To evaluate the results of therapy of invasive pulmonary aspergillesis (IPA) in one medical center from 2000 to 2005. MATERIAL AND METHODS: Diagnosis of IPA was made according to the International criteria. Incidence of verified IPA was 2%, probable--84%, possible--14%. RESULTS: IPA was diagnosed in 50 cases in 49 patients aged 16- 78 years, median 35. Most of the patients consisted of acute leukemia cases (54%). Intensive cytostatic therapy was given in 41% cases. In 54% IPA developed in critical neutropenia, median of duration of which being 29 days (3 to 144 days). 29 patients received glucocorticoid drugs. In diagnosis of IPA Aspergillus spp was isolated in 46% cases (A. fumigatus-59%, A. flavus-29%, A. niger-4%, A-versicolor-4%, in 1 (4%) case identification was not made. Positive antigen Aspergillus was detected in 27 cases. All the patients had pulmonary involvement detected at x-ray or computed tomography. Coincidence of pulmonary lesions seen at x-rays and computer tomograms was only in 30% patients. Cure was achieved in 44%, lethality was 56%. Overall survival in IPA for 90 days was 47%. Amphotericine was effective in 29%. Voriconasol--in 3 of 5 patients, kaspofungin--in 3 of 7. Surgical treatment was given to 4 patients. CONCLUSION: Lethality in IPA for 5 years when basic therapy was amfotericin B reached 56%. Reduction of lethality can be achieved due to early diagnosis of the infection and administration of voriconasol at the initial stage of IPA. It is necessary to conduct multicenter studies to ascertain indications for combined antifungal therapy.

Adolescent↗
PubMed2004

[Potentialities of high-resolution computed tomography in diagnosis of pulmonary lesions after bone marrow transplantation in blood diseases].

AIM: To study characteristics of a skialogical picture of pulmonary parenchyma and roentgenomorphological signs of inflammatory changes before and after bone marrow transplantation (BMT); relationship between the data of high-resolution computed tomography (HRCT) and clinical data. MATERIAL AND METHODS: HRCT (computer tomograph of the third generation "Somatom CR-3") was made in fever, changes in physical examination in patients (n = 28) after BMT from November 2001 to January 2003. BMT was made in myelomic disease, lymphogranulomatosis, acute leukemia, chronic myeloid leukemia, lymphosarcoma, autoimmune hemolytic anemia. RESULTS: Twenty four patients were examined before BMT. Of them, 18 patients had roentgenomorphological changes of the parenchyma, primarily, diffuse. Three patients were examined during conditioning, two cases had signs of toxic pulmonitis. One day after allo-BMT all the patients exhibited lowering of densitometric values of pulmonary tissue by 70 HU vs the baseline. Infectious affection of the lungs was diagnosed in 13 cases during day 0-100. From day 100 after allo-BMT 7 recipients were observed. In 6 cases the changes resulted from transplant against host reaction. Infectious affection of pulmonary tissue was observed in 1 case. Characteristic x-ray picture of pulmonary stroma in secondary disease was determined. CONCLUSION: For early diagnosis of pneumonia in myelotoxic agranulocytosis it is necessary to make examination by HRCT before BMT. HRCT of the chest is indicated in even minor changes in the clinical picture. It is necessary to perform a control over water-electrolyte balance and active respiratory exercise in the course of conditioning. Viral pneumonias show the picture of metainflammatory changes for a long time. Fungal pneumonias tend to recurrence at "previous site". HRCT examination of the pulmonary tissue provides more information about pulmonary tissue in patients with secondary disease.

Adolescent↗
PubMed2004

[In vitro cell adhesion and integrin expression by calcium ionophore-treated mononuclear cells from patients with acute myeloid leukemia].

As shown elsewhere, cultured acute myeloid leukaemia blasts acquire certain characteristics of dendritic cells upon stimulation with cytokines and calcium ionophore. The ability of leukaemia-derived dendritic-like cells to express immune costimulatory molecules and dendritic cell marker CD83 has been extensively investigated. Although migratory capacity is a major attribute of dendritic cells, the ability of in vitro modified blasts for adhesion, chemotaxis and homing remain elusive. In the present paper, we show that after stimulation with calcium ionophore acute myeloid leukaemia blasts as well as normal dendritic cell precursors demonstrate increased capacity of binding fibronectin and denatured collagen. The expression pattern of integrins on dendritic-like leukaemic cells in general closely resembles that of monocyte-derived dendritic cells, however, variation in cell properties isolated from blood of individual patients are observed.

Acute Disease↗