[Prophylaxis of fungal infection in patients with hematologic neoplasms and severe neutropenia after high-dose chemotherapy]. / Profilaktika gribkovoi infektsii u bol'nykh s gematologicheskimi novoobrazovaniiami i glubokoi neitropeniei, razvivsheisia posle provedeniia vysokodoznoi khimioterapii.

Infection is one of the main causes of death in patients with hemoblastoses. Within the last years there was observed an increase in the ratio of fungal infections in the structure of mortality among hematologic patients with neutropenia. The present study was aimed at comparative estimation of the efficacy of the prophylactic use of various azole antifungal agents in patients with hematologic neoplasms and severe neutropenia. The trial enrolled 88 patients comparable by the diagnosis and chemotherapy characteristics, in whom severe neutropenia developed after intensive therapy. Antifungal drugs were used prophylactically when the neutrophil count lowered below 1.0 x 10(9)/l until its increasing above 1.0 x 10(9)/l or when the signs of fungal infection were evident. Itraconazole was used in cyclodextrin solution in 30 patients in a dose of 0.2 g orally twice a day and fluconazole was used in capsules in 24 patients in a dose of 0.2 g orally once a day. The results were compared with those of the ketoconazole use in a dose of 0.2 g orally twice a day (n = 34). The frequency of fungal infection proved by the clinical documentation was 20.5% in the ketoconazole group (k) (7 out of 34 patients), 8.3% in the fluconazole group (f) (2 out of 24 patients) and 6.6% in the itraconazole group (i) (2 out of 30 patients), p (k-f) = 0.21, p (k-i) = 0.11 and p (f-i) = 0.74. The frequency of fungal infection proved by the microbiological documentation was statistically much higher in the ketoconazole group (38.2%) vs. the fluconazole group (8.3%) (p = 0.013) and the itraconazole group (6.6%) (p = 0.004). The prophylactic use of itraconazole and fluconazole was efficient in preventing development of invasive mycoses in the patients with hemoblastoses and severe neutropenia. Their efficacy was much higher than that of ketoconazole.

[Use of Mabtera (rituximab) in treating patients with refractory courses of B-cell lymphoma, along with high-dose chemotherapy and autologous transplantation of hematopoietic stem cells]. / Primenenie mabtery (rituksimab) u bol'nykh refrakternym techeniem B-kletochnym limfom, poluchaiushchikh vysokodoznuiu khimoterapiiu s autologichenoi transplanttatsiei kletok-predshestvennits gemopoéza.

AIM: To study efficacy of rituximab in patients with resistant B-cell lymphoma on high-dose chemotherapy. MATERIAL AND METHODS: From September 2000 to April 2002 we studied efficacy and tolerance of rituximab at different stages of high-dose chemotherapy. The treatment was given to 10 patients with histologically verified CD20+ non-Hodgkin's lymphoma: diffuse large-cell (n = 4), Berkitt's (n = 2), follicular (n = 3), mantle-cell (n = 1). Five patients with diffuse large-cell lymphoma and Berkitt's lymphoma had a primary resistant course of the disease, one patient with diffuse large-cell lymphoma had a refractory recurrence. Follicular and mantle-cell lymphomas were characterized by a resistant course and large tumor masses. The patients received 1-2 courses of induction chemotherapy with dexa-BEAM with collection of peripheral stem cells followed by high-dose chemotherapy (BEAM-9, CBV + mitoxantron-1) with transplantation of autologous stem blood cells. Rituximab infusion (375 mg/m2) was conducted before the collection of the stem cells, prior to high-dose chemotherapy and in posttransplantation period after recovery of hemopoiesis. RESULTS: 4 patients achieved complete remission, 3-partial remission, 2 had progression and 1-stabilization. In mean follow-up 11 (2-20) months 7 of 10 patients were alive, overall survival being 15 +/- 2.4 months (95% confidence interval 10-19.7), median was not reached. 5 patients are in complete remission: 2 of them without further treatment, 3-after progression and repeat therapy including rituximab and interferon-alpha or rotuximab and CHOP chemotherapy. CONCLUSION: The addition of rituximab can improve the results of high-dose chemotherapy of patients with non-Hodgkin's lymphoma resistant to standard doses of cytostatics. Repeat use of this drug can be effective in some patients with progression after high-dose chemotherapy with rituximab.

[Benzylpenicillin efficacy for neutropenic infection prophylaxis in patients with cancer and postcytostatic neutropenia]. / Effektivnost' naznacheniia benzilpenitsillina dlia profilaktiki neitropenicheskoi infektsii u bol'nykh s opukholevymi zabolevaniiami i posttsitostaticheskoi neitropeniei.

Evaluation of benzylpenicillin (penicillin G) effect for infection prophylaxis at the oncological patients with severe postcytostatic neutropenia was performed. All the patients with neutrophils levels lower than 0.5 x 10(9)/L were recommended to use antibiotics for infection prophylaxis. Test-group (n = 40) used ciprofloxacin (0.5 g twice daily, per os) combined with benzylpenicillin (1.0 g four times daily, i/v); control group was treated by ciprofloxacin in the same dose only. Combination with benzylpenicillin resulted in statistically significant reduction of infections frequency among oncological patients.

[Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis]. / Izuchenie chuvstvitel'nosti opukholevykh kletok bol'nykh ostrym leikozom k tsitokinam i ikh sochetannomu primeneniiu s khimiopreparatami in vitro metodom MTT-analiza.

MTT analysis has yielded data on the sensitivity of leukemia cells isolated from 64 patients with acute leukemia to the cytokines G-KSF?, GM-KSF, interferon-alpha 2b and their combined use with drugs, such as cytosar, vepeside, doxorubicin, vincrastine, L-asparaginase. The mean in vitro survival of leukemia cells in children with acute lymphoblast cell leukemia (ALCL) was 1.9 times less than that in acute myeloblast cell leukemia (AMCL) (p < 0.001), that in new cases of ALL was 2.3 times less than in relapses (p = 0.024). The stimulating effect of GM-KSF on the survival rates of leukemia cells was seen in 64.7% of patients with AML. That of GM-KSF was recorded in 21.4% of cases. The survival of lymphoblast cells isolated from children with ALL did not differ greatly in the absolute majority of cases (by more than 30%) in the presence of growth factor in the medium. The cytotoxicity of XII with medium growth factor decreased in most cases. However, some cases (more frequently in AML than ALCL) displayed a higher cytotoxicity of XII, particularly cytosar in the presence of G-KSF and GM-KSFG; LC50 of Ara-C decreased by 30% or more in the presence of growth factor in 36% of patients. Incubation with interferon alpha 2b caused a reduction in the survival of leukemia cells, which was more pronounced in children with ALL. Interferon-alpha 2b caused an increase in the cytotoxic effect of XII on leukemia cells in ALL to a greater extent; cytosar, vepeside, and doxorubicin enhanced the effect by 1.47, 1.39, and 2.35 times, respectively.

Effects of CSFS and their combinations with chemotherapeutic agents (CH) on leukemic blasts (LB) in children (MTT-assay).

Thirty-five samples of bone marrow (BM) from 17 patients (pts) with ALL and 18 pts with AML (aged 9 m-20 yrs, median 7.7 yrs) were obtained. Using MTT-assay the sensitivity of LB to Ara-C, VP-16, DOX, G(GM)-CSF and their combinations was measured. LC50 was higher in pts with AML than with ALL: to Ara-C 1.94-fold (p < 0.05), to VP-16 1.62-fold (p = 0.2), to DOX 3.9-fold (p < 0.05). Incubation with G-CSF increased the viability of ALL and AML LB--104.3% and 104.1% respectively (the viability of leukemic cells without CSF accepted as 100%). Incubation with GM-CSF decreased the viability of ALL LB (96.5%) and increased the viability of AML LB (139.1%) (p = 0.08). Combining Ara-C with G- or GM-CSF resulted in equal or increased LC50 (compared with LC50 of Ara-C alone) in 100% cases of AML. For ALL: LC50 of "Ara-C+G-CSF" was equal or increased in 63.6% cases; LC50 of "Ara-C+GM-CSF"-in 62.5%. For VP-16 and DOX all pts (ALL, AML) except two had equal or increased LC50 of "CH+CSF" (compared with LC50 of CH alone). These data show: 1) AML LB were less sensitive to the investigated CH than ALL LB. 2) The LC50 of "CH+CSF" was equal or increased compared to the LC50 of CH for the absolute majority of cases with VP-16 and DOX. The same results were obtained with AML and in about 60% cases of ALL. The effect of the increasing of cytototoxity of CH in presence of CSF probably exists mostly at higher concentrations of CH than those that can be achieved in clinical practice.

[The role of high-dose chemotherapy with hemopoietic stem cell transplantation in the treatment of breast cancer with unfavorable prognosis]. / Rol' vysokodoznoi khimioterapii s transplantatsiei kletok- predshestvennikov gemopoèza pri lechenii prognosticheski neblagopriiatnykh form raka molochnoi zhelezy.

High-dose chemotherapy using transplantation of hemopoietic precursor cells offers much advantage for treatment of prognostically unfavorable cancers of the breast. Both experimental and clinical evidence points to a potential of raising antitumor effect by increased dosage of chemical drugs. Clinical studies using high-dose chemotherapy for treating patients with stage II-III tumors or with greater than or equal to 10 positive axillary lymph nodes, and locally-advanced and disseminated tumor established a relative rise in overall and recurrence-free survival, as compared with standard treatment. Hazardous cytopenia and related complications can be significantly reduced when hemopoietic precursor cells are transplanted from peripheral blood.

[Superhigh-dosage chemotherapy with the transplantation of autologous hemopoietic precursor cells in patients with a prognostically unfavorable relapse and resistant course of lymphogranulomatosis]. / Sverkhvysokodoznaia khimioterapiia s transplantatsiei autologichnykh kletok predshestvennikov gemopoéza u bol'nykh s prognosticheski neblagopriiatnym retsidivom i rezistentnym techeniem limfogranulematoza.

Eighteen patients with relapsed or refractory Hodgkin's disease (HD) have been treated with high-dose chemotherapy (BEAM regimen) followed by autologous peripheral stem cells and/or bone marrow rescue. There were no treatment-related deaths. Overall response rate was 82%. With a median follow-up of 10 months (3-24 months) overall survival and freedom from progression were 100 and 94% (95% confidence interval 58-97%), respectively. The use of peripheral stem cells in addition to bone marrow resulted in a significant shortening of the time to engraftment (p < 0.01). The BEAM regimen is an effective conditioning schedule which is well tolerated.

[Use of autologous hematopoietic stem cells from peripheral blood for transplantation in patients with hematologic and solid neoplasms after high-dose chemotherapy]. / Primenenie autologichenykh kletok-predshestvennikov gemopoéza ia perifericheskoi krovi dlia transplantatsii u bol'nykh s gematologicheskimi i solidnymi novoobrazovaniiami posle vysokodoznoi khimioterapii.

Peripheral mononuclears under normal hemopoiesis and after chemotherapy or/and cytokin were isolated on blood cell separator and cryopreserved. The cells from 22 patients with different hematological and solid malignancies were examined. Mononuclears with high content of hemopoiesis precursors may be collected rapidly after stimulation. Fast and persistent recovery of hemopoiesis in transplantation of this material after superhigh-dose chemotherapy of prognostically unfavourable patients is demonstrated. Cytokin (granulocytic and granulocytic-macrophagal growth factors) promoted fast and reliable production of sufficient quantities of peripheral blood hemopoiesis cells precursors.

[The induction of tolerance in mice for a human melanoma graft]. / Induktsiia tolerantnosti u myshei k transplantatu melanomy cheloveka.

Mouse skin allografts and intramuscular BRO human melanoma xenografts were successfully established in phenotypically normal mice after inducing immunological tolerance in the recipients. Tolerance was achieved by inoculating allogenic embryonic liver cells after the whole-body irradiation. No immunological rejection was evident in BRO xenografts for 34 days after transplantation. During this period the BRO cells invaded neighboring tissues and formed distant micrometastases in the lungs.

[Modeling of the "universal" bone marrow using monoclonal antibodies]. / Modelirovanie "universal'nogo" kostnogo mozga s pomoshch'iu monoklonal'nykh antitel.

The data on the application of monoclonal antibodies (ICO-10) and rabbit complement for working the conditions of allogeneic bone marrow transplantation are presented in the paper. The treatment with monoclonal antibodies and bone marrow complement from BALB/c mice for 2 times prevented the development of transplant versus host reaction and completely protected lethally irradiated (CBA X X C57B1/6)FI mice-recipients from death. Thymus atrophy and the absence of T-cells in the peripheral blood was observed in these mice. The erythrocytes had markers characteristic of BALB/c and (CBA X C57B1/6)FI mice. Mouse splenocytes did not respond to the cells of donors and recipients in mixed lymphocyte culture reaction.

[ICO-10 monoclonal antibodies to the Thy-1 antigen]. / Monoklonal'nye antitela IKO-10 k antigenu Thy-1.

Mouse monoclonal antibodies (MAB) ICO-10 to Thy-1 antigen were obtained. MAB ICO-10 reacted in indirect immunofluorescence test with 5.7 +/- 0.8% human thymocytes. Antibodies did not react with granulocytes, monocytes, T- and non-T cells from peripheral blood, and with marrow cells of healthy donors. MAB ICO-10 reacted with blast cells from 25 of 53 patients with T-cell acute lymphoblastic leukemia (ALL), from 2 of 5 patients with B-cell ALL. This antigen was absent on blood and marrow cells from some patients with ALL, 80 patients with chronic lymphoid leukemia, 54 patients with chronic granulocytic leukemia at the stage of blastic crisis, 128 patients with acute nonlymphoblastic leukemia. Antibodies are specifically bound to thymocytes and spleen cells of Thy 1.1 and Thy 1.2 mice. MAB ICO-10 detect Thy-1 antigen expressed on human hematopoietic cells. MAB ICO-10 may be applied for human leukemia and lymphoma immune diagnosis.

[Inhibition of the growth of the Ca-755 tumor in mice with reconstitution of hematopoiesis]. / Tormozhenie rosta opukholi Ca-755 u myshei s rekonstitutsiei krovetvoreniia.

Data on the growth inhibition of Ca-755 tumor transplanted to mice two months after hemopoiesis recovery with syngeneic bone marrow cells or allogeneic fetal liver are presented.

[Quantitative changes in the cellular makeup of the spleen in mice infected with the Rauscher leukemia virus and Brucella abortus]. / Kolichestvennye izmeneniia kletochnogo sostava selezenki myshei, zarazhennykh virusom leikoza Raushera i Brucella abortus.

Changes in the absolute number of splenic cells of mice infected with Rauscher leukemia virus (RLV) and a day later--with living Brucella (BA) were studied. The increase in the absolute number of splenic cells of mice infected with RLV + BA was initially caused by the lymphoid tissue reaction to Brycella and then by the development of leukemia. The number of reticular cells in the spleen appeared to be larger than the control (RLV) within all observation periods; the number of basophilic normocytes amounted to the control, but an increase in the erythroblasts number was noted a week later and reached the control level by the 30th day, practically being unchanged subsequently. In mice receiving RLV + BA there was the increased monocyte, plasmatic cell, megakaryocyte, myeloid series cell count. The shift of splenic granulocytes to the "left", the development of leukocytosis, blood neutrophilia, in particular, lagged 1--2 weeks behind in such mice. The number of normocytes getting into the blood was decreased. All this would result in a significant extension of the lifespan in mice RLV + BA.

[Increase in the content of thymus hormone sensitive rosette-forming cell precursors in the spleen of mice vaccinated against smallpox]. / Uvelichenie soderzhaniia chuvstvitel'nykh k gormonu timusa predshestvennikov rozetkoobrazuiushchikh kletok v selezenke vaktsinirovannykh ospennoi vaktsinoi myshei.

Smallpox vaccine injection to 2-month-old C57BL/6j female mice caused during the first days significant rise in the number of precursor cells of rosette-forming lymphocytes, sensitive to the differentiating thymus extract effect. The number of these cells returned to the normal level by the 10th day after vaccination.

[The effect of Trichinella spiralis on the susceptibility and antibody production to vaccinia virus]. / Deîstvie Trichinella spiralis na vospriimchivost' i obrazovanie antitel k virusu ospovaktsiny

Trichinella spiralis exerts an immunodepressive effect on production of antihemagglutinins to vaccinia virus in mice, increases the susceptibility to the virus in mice and rabbits. Deaths of mice inoculated with vaccine virus and generalization of the vaccination process in rabbits were observed at 33 days of invasion.

[Approach to the development of an actovaccine using vaccinia virus as a model]. / O podkhode k pazrabotke aktovaktsiny na modeli virusa ospovaktsiny

Injection of living vaccinia virus to the mesenteric vein of rabbits leads to its accumulation in liver in high concentration. In the other series of experiments vaccinia virus inactivated with gamma-radiation was inoculated into the mesenteric vein. Later on the animals were sacrificed at various dates. Homogenates were prepared from their liver. Comparative study of these homogenates made it possible to reveal increased immunogenic activity of homogenate obtained 24 hours after intravenous inoculation of inactivated vaccinia virus into animals. Immunogenic activity of this homogenate was more clearly manifested than immunogenic activity of the antigen itself--inactivated vaccinia vorus. Neither original inactivated vaccinia virus nor inactivated virus absorbed by Kupffer cells induced antibody formation. It is supposed that vaccines may be prepared from various viruses or tumor cells treated with macrophages with subsequent chemical extraction of the most immunogenic fraction.

[Effect of Trichinella spiralis infection on the development of Rauscher leukemia]. / Vliianie invazii Trichinella spiralis na razvitie leikoza Raushera

The influence of Trichinella spiralis on the course of Rausher leukemia in mice was studied. Inoculation of mice with Trichinella spiralis larvae 15, 16 and 30 days before infection with Rausher leukemia virus was shown to stimulate splenomegaly, whereas preinoculation of Rausher leukemia virus at 6, 12 and 18 days before infection with Trichinella spiralis resulted in inhibition of splenomegaly. Under the experimental conditions used, no effect of T. spiralis on reproduction of Rausher leukemia virus was observed, as virus titers in the plasm of mice with marked stimulation or inhibition of splenomegaly were identical and did not differ from those in mice without Trichinella spiralis invasion.