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Biomedical subjects

V G Savchenko

Publications and source records attributed to V G Savchenko.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Study of the time course of mixed chimerism by fluorescent in situ hybridization in patients with chronic myeloid leukemia after allogenic transplantation of bone marrow].

AIM: To determine the type of chimerism in patients with chronic myeloid leukemia (CML) in various periods after allogenic transplantation of bone marrow (TBM) and its association with subsequent relapse. MATERIALS AND METHODS: Ten patients were examined after allogenic TBM, which was performed during the chronic phase of CML in 9 patients and during acceleration phase in 1. Two patients received therapy with donor lymphocytes during relapse after transplantation. Time course of chimerism and minimum residual illness was studied by standard cytogenetic methods, fluorescent in situ hybridization (FISH) with DNA probes to centromer sites of X and Y chromosomes and BCR and ABL genes. The studies were carried out 30, 60, 90, 180 days, 9 months, 1 year, and then every 6 months after transplantation. RESULTS: Mixed chimerism was observed in all patients during 9 months after TBM. The count of host cells was 0.1-5.8% in 8 patients; later the count of autologous cells was less than 1% in 5 patients, and in 3 patients complete donor chimerism was observed. Clinical hematological remission was stable in these patients. Relapses of leukemia with 40 and 83.1% host cells occurred in 2 patients 13 and 23 months after transplantation, respectively. Donor lymphocytes were transfused in order to induce the graft versus host effect, and in patient No. 2 restoration of donor hemopoiesis was attained. CONCLUSION: Highly sensitive FISH method with DNA probe to centromer sites of X and Y chromosomes detects early relapse of the disease and demonstrates the time course of donor hemopoiesis recovery after transfusion of donor lymphocytes. The data indicate that 9 months after transplantation molecular cytogenetic studies should be carried out more often (once a month), particularly in patients with poor prognosis, for earlier detection of the relapse and beginning of immunotherapy.

Adult↗
PubMed2001

[Induction of co-stimulatory molecules on the surface of blast cells in patients with acute myeloid leukemia].

AIM: To compare the capacity of ionophore for calcium ions and growth factors (granulocytic-macrophagal colony-stimulating factor, interleukin-4, tumor necrosis factor) to induce costimulatory molecules on the surface of blast cells from patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: The study was carried out in 6 patients with primary and resistant AML using culturing and flow cytometry. RESULTS: Blast cells obtained from patients during diagnosis of AML and after drug therapy of resistant AML acquire the dendrite phenotype under the effects of growth factors and Ca ion ionophore. CONCLUSION: Calcium metabolism modulators can be used for creation of antileukemic vaccines.

Acute Disease↗
PubMed2001

[Apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes as evidenced by trephine biopsy].

AIM: To clarify the effect of cyclosporin A (CSA) on the apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes by trepanobiopsy evidence. MATERIALS AND METHODS: The TUNEL immunohistochemical assay was used to study apoptosis of bone marrow cells in the histological specimens from 24 patients: 8 with refractory anemia (RA), 8 with acute small-proportion leukemias [RA with excessive blasts (RAEB) + RAEB in transformation (RAEBt)], 3 with acute non-lymphoblastic leukemia (ANLL), 5 with lymphogranulomatosis (LGM). Control apoptosis examination was made in 10 patients treated with CSA. The proliferative activity of bone marrow cell was evaluated by bone marrow histological specimens from 10 patients (8 patients with RA and 2 with RAEB + RAEBt) at the onset of disease and during CSA therapy in the immunohistochemical test with primary nuclear antigen Ki-67 antigen antibodies. Changes in the proliferative activity and degree of apoptosis of bone marrow cells were assessed in relation to the cellularity detectable by the histological specimens. RESULTS: Patients with RA showed an increase in bone marrow cell apoptosis to 25.375 +/- 6.874 (-10.8 +/- 5.122 and 8.333 +/- 5.84 in controls and ANLL patients, respectively). The cells of hemopoiesis and stromal microenvironment are in the process of cell death. Higher bone marrow cellularity is observed in CSA-treated patients at clinical and hematological remission, which is followed by rises in the index of proliferation and the degree of apoptosis. CONCLUSION: The clinical effect of CSA in patients with aplastic syndromes is induced by its direct or mediated stimulating effect on pluripotent stem cells of hemopoiesis, by increasing bone marrow cellularity at the expense of clonal and/or normal hemopoiesis.

Acute Disease↗
PubMed2001

[Effectiveness of cyclosporin A in the treatment of adult patients with aplastic anemia].

AIM: To evaluate the efficacy of cyclosporin A (CyA) at different stages of immunosuppressive therapy (IST) in patients with aplastic anemia (AA). MATERIALS AND METHODS: The efficacy of CyA was studied in 56 patients with AA. The agent was orally given in an initial dose of 10 mg/kg as solution or capsules. Its daily dose during a treatment course varies with the serum CyA levels and clinical tolerance. CyA was used in 17 patients at the first stage of treatment, in 8 with recurrent AA, and in 31 after ineffective previous therapy (antilymphocytic globulin therapy--ALGT, splenectomy). Erythropoiesis was evaluated by the count of erythrokaryocytes and by relative erythroid hyperplasia of the bone marrow and by using erythrokaryocytic PAS reaction, by calculating the total count of sideroblasts and ringed sideroblasts. RESULTS: A positive response was obtained in 41% of the patients with AA. Its pattern depended on the severity of AA, on CyA use regimens, and treatment duration: when treatment with CyA lasted 6-12 months, its efficacy considerably increased (positive responses in severe AA and mild AA being in 64 and 94%, respectively). It has been found that high (over 6%) baseline bone marrow ringed sideroblasts in patients with AA may be regarded as a poor predictor in the context of the efficacy of this agent. CONCLUSION: CyA is recommended for combined IST in patients with AA at the second stage of treatment (after antilymphocytic globulin administration) in order to perform long-term (12-month) immunosuppression by choosing the optimum dose on an individual basis and by continuously monitoring the quality of a response.

Adolescent↗
PubMed2000

[The effect of polychemotherapy on the oral mucosa in patients with acute myeloblastic leukemia].

Oral mucosa was examined in 23 patients with acute myeloblastic leukemia before and after cytostatic polychemotherapy. Lesions of the oral mucosa were observed in all patients after polychemotherapy: its color was changed, atrophic processes developed in it, and salivary secretion was impaired. Destructive ulcerative changes were revealed in 35% cases; terms of their appearance, regression, and epithelialization were established and a clear-cut correlation between their development and severity of leukocytopenia was detected. Ranging of stomatitis severity is proposed, according to which medium-severe stomatitis predominates in this patient population. The study will help develop more effective approaches to prevention and treatment of oral complications and improve the results of therapy of this most grave category of hematological patients.

Adolescent↗
PubMed2000

[The induction of the antitumor activity of T-lymphocytes by antigen-presenting cells obtained from the blast cells of patients with acute leukemias].

AIM: To produce antigen-presenting cells (APC) from tumor cells of patients with acute leukemia and to induce autologous cytotoxic tumor-specific T-lymphocytes in vivo and in vitro. MATERIAL AND METHODS: Culture examinations, flow cytofluorometry were made in 3 patients with acute myeloid leukemia (AML) and 1 patient with acute lymphoblastic leukemia (ALL). RESULTS: Culturing of blast cells in the presence of growth factors produced APC in 4 patients with acute leukemia. The use of fibronectin layer with added collagen proved most effective for the above production. In culture, APC induced autologous tumor-specific T-lymphocytes which selectively lysed tumor cells. Pilot clinical trial was made of dendritic cells suspension in a patient with resistant AML. CONCLUSION: A new perspective immunotherapy of acute leukemia is proposed.

Acute Disease↗
PubMed2000

[The efficacy of high-dose chemotherapy and the transplantation of autologous hemopoietic cells in lymphogranulomatosis].

AIM: To determine clinical effectiveness of high-dose polychemotherapy (PCT) and transplantation of autologous hemopoietic cells (TAHC) in patients with lymphogranulomatosis (LGM). MATERIAL AND METHODS: 27 LGM patients aged 16-42 years who have undergone TAHC after high-dose PCT (BEAM--17 patients or CBV--10 patients). 4 patients given high-dose PCT were in the first-second complete remission (CR), 7 patients--in the first partial remission (PR). Prior to TAHC, 8 patients had one, two and more relapses of LGM, and 8 patients had no remission at all. Bone marrow, hemopoietic blood cells and both were transplanted to 17, 2 and 8 patients, respectively. Mobilization of hemopoietic blood cells and stimulation of hemopoiesis after TAHC were achieved using colony-stimulating factors. RESULTS: The treatment resulted in CR or PR (from 6 to 95 months) in 70.4% of patients. The remission duration varied depending on the disease phase at transplantation. Four patients who underwent TAHC in PR maintained it for 13-95 months (median 47.5 months). Lasting remissions (29-59 months) were achieved in 42.9 and 37.5% of patients who underwent TAHC in the first PR or in recurrent LGM. None of the patients was in remission longer than 2 years after TAHC if high-dose PCT was conducted in advanced tumor process due to resistant LGM or inadequate previous treatment. Infectious complications lethality early after the transplantation reached 7.4%(2 patients). CONCLUSION: High-dose PCT followed by TAHC is effective in LGM if the tumor is chemosensitive.

Adolescent↗
PubMed1999

[Results of clinical trials in the treatment of acute myeloid leukemia in adults during a 7-year period].

AIM: Comparison of effectiveness of induction regimens varying in intensity and maintenance variants in patients with acute myeloid leukemia (AML) included in a randomised multicenter trial. MATERIALS AND METHODS: Clinical trial 1 enrolled 185 AML patients. Vepesid-free induction was used in 85 patients (group 1), induction with vepesid--in 99 patients (group 2). 223 AML patients entered trial 2. Of them 37 patients were treated for 3 years 7 + 3 with daunorubicin in the dose 45 mg/m2 in the induction phase (group 1), 85 and 101 patients received 7 + 3 with daunorubicin for a year in the dose 45 mg/m2 and 60 mg/m2, respectively, (group 2 and 3). RESULTS: For group 1 in trial 1 the remission rate, early lethality, resistance were, respectively, 60, 20 and 20%, respectively. For group 2 in trial 1--66, 22 and 12%, respectively. 5-year recurrence-free survival reached 32 and 37% for group 1 and 2, respectively. For trial 2 relevant figures made up 75.5, 16.2, 8.1% for group 1; 60, 17.6 and 22.4% for group 2; 63, 20.8 and 16% for group 3, respectively. The 3.5-year recurrence-free survival in groups 1, 2 and 3, was 16, 46 and 50%, respectively. For both trials, the differences between the groups were insignificant. CONCLUSION: The results evidence that the treatment can be shorter (not 3 but 1 year or even 6 months), the induction more intensive (the dose of anthracycline antibiotics can be elevated up to 60 mg/m2 without a rise in early lethality).

Acute Disease↗
PubMed1999

[Effectiveness of trans-retinoic acid in the treatment of acute promyelocytic leukemia: initial results of a multicenter study].

AIM: Evaluation of trans-retinoic acid (ATRA) in combination with cytostatic drugs in treatment of acute promyelocytic leukemia (APL). MATERIALS AND METHODS: In a multicenter study APL was treated according to protocols APL 01.97 and APL 06.87 in 28 patients (14 males and 14 females, median age 36 years). RESULTS: Administration of ATRA in combination with standard program 7 + 3 (cytosine-arabinoside 100 mg/m2 twice a day v.v. day 1-7, daunorubicin 60 mg/m2 v.v. day 1-3) induced a complete remission in 25 patients (90%). Early lethality was 10% (3 patients died). Resistant APL was not registered. Retinoid syndrome was diagnosed in 15 patients, one patient died. 2-year overall and recurrence-free survival made up 72 and 82%, respectively. CONCLUSION: ATRA combination with cytosine-arabinoside and daunorubicin is a novel treatment of acute promyelocytic leukemia providing a high rate of complete remission and long-term survival.

Adolescent↗
PubMed1999

[Effectiveness of allogeneic bone marrow transplantation in patients with acute leukemia in complete remission and in patients with chronic myeloid leukemia during the chronic phase].

AIM: To study clinical efficiency of allogenic bone marrow transplantation (ABMT) in patients with acute leukemia (AL) in the first remission and in patients with chronic myeloid leukemia (CML) in chronic phase; to analyse overall and recurrence-free survival in relation to the diagnosis and age. MATERIALS AND METHODS: 26 patients with AL and 24 ones with CML (29 males and 21 females) were subjected to ABMT within 10 last years. Median of age in AL and CML was 24.5 and 25.5 years, median of the time since the diagnosis was 9 and 13 months, respectively. Follow-up since the ABMT made up 67.5 months (31-107) and 38 months (6-108), respectively. Conditioning was made with cyclophosphamide (120 mg/kg) plus total radiation of the body (12 Gy) in 16 patients, myelosan (mileran) in a dose 16 mg/kg plus cyclophosphane (120 mg/kg) in 34 patients. The marrow was taken from HLA-identical sibs, enzygotic twins (5 recipients). Cytogenetic investigations were made in CML. The retention of the transplant was controlled by immunological and molecular tests. RESULTS: Among AL patients 50% are still alive. Probability of 80-month survival reached 55%, 110 months--42%. Probable recurrence-free survival was 78%. All the patients are in a complete clinico-hematological remission. Among CML patients 75% are still alive. Of them 89% had a complete hematological remission, 72% are in a complete hematological and cytogenetic remission. Probable 110 month survival equals 75%, probability to survive without recurrence--52%. Early lethality (100 days) of toxic and infectious complications was as low as 10 and 6%, respectively. Frequency of lethal acute secondary disease was under 8%. CONCLUSION: ABMT made in AL patients during the first complete remission and in CML patients in the chronic phase brings about very good results which are much better than after routine cytostatic chemotherapy.

Acute Disease↗
PubMed1999

[Aplastic anemia and viral hepatitis (posthepatitic aplastic anemia)].

AIM: To validate up-to-date policy of immunosuppressive therapy of patients with aplastic anemia (AA) which has developed either at acute or chronic phase of viral hepatitis. MATERIALS AND METHODS: 16 patients with AA detected within 6 months (9 patients) or 12-36 months (7 patients) after acute viral hepatitis received immunosuppressive therapy (antilymphocytic globulin, cyclosporin A, splenectomy). RESULTS: Posthepatitis aplastic anemias ran a severe and treatment-resistant course in most cases. The immunosuppressive therapy produced a response in 44% of the patients. AA following acute viral hepatitis demands intensive and long-term immunosuppressive therapy with antilymphocytic globulin, cyclosporin A, splenectomy (in some cases) to achieve a persistent clinicohematological remission.

Adolescent↗
PubMed1999

[Immobilized forms of daunorubicin in patients with acute leukemia].

AIM: To study pharmacokinetics of liposomal daunorubicine DaunoXome and daunorubicine (rubomycin) associated with red cells: to assess their effectiveness and toxicity in patients with acute leukemia. MATERIALS AND METHODS: 7 patients with resistant or recurrent acute leukemia entered the trial. Of them 2 patients had acute myeloid leukemia. They received DaunoXome in dose 100 mg in days 1, 2 and 3 of 7 + 3 program. 1 patient had pretreated acute promyelocytic leukemia. This patient received 5-day course of DaunoXome in a dose 100 mg in the presence of ATRA therapy. 4 patients were given single dose daunorubicin associated with autoerythrocytes in the courses RACOP and 7 + 3 in a dose 45 mg/m2. Concentrations of free, bound and liposomal daunorubicin were determined spectrofluorimetrically in chlorophorm extracts of plasm, blood, liquor and bone marrow specimens. RESULTS: Immobilization of daunorubicin on the red cells and liposomes changes pharmacokinetics of the drug: peak concentrations change and the area under the concentration curve increases. Tolerance of DaunoXome and daunorubicine associated with red cells was satisfactory in all the cases: clinical and echo-CG signs of cordiotoxicity were absent, myelotoxicity was similar to that of free daunorubicine. DaunoXome was effective in 2 of 3 patients with acute myeloblastic leukemia. CONCLUSION: The findings are of practical interest for physicians designing new programs of therapy of acute leukemia.

Adolescent↗
PubMed1999

[Priorities in research of hemoblastosis].

Evidence is provided for that it is urgent to elaborate a problem of hemoblastosis and hemopoietic depressions within the framework of a special federal research and technological programme. Priorities of research lines in this areas, trends of their development till 2005 are presented.

Hematologic Neoplasms↗
PubMed1998

[Use of meropenem in patients with neutropenia].

Meropenem was used in the treatment of 14 infectious complications in 11 patients including 8 with acute myeloid leukemia due to the cytostatic therapy, 1 with chronic myeloid leukemia, 1 with aplastic anemia and 1 with acute intermittent porphyria. At the moment of the meropenem use critical neutropenia (less than 500 granulocytes per 1 ml) in 11 cases (79 per cent) was stated. The drug was administered as intravenous infusions in a dose of 1 g every 8 hours for 4 to 41 days (the median of 11 days). 9 out of the 14 infectious complications were cured (the body temperature normalized and all the inflammation foci were eliminated), among them 6 out of 8 pyocyanic sepsis. Eradication of gram-negative bacteria was observed in 8 out of 10 cultures of the biological materials. No toxic complications or electrolytic disorders due to the drug use were recorded. The drug tolerance was good.

Adolescent↗