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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.

The authors examined 8 patients with pretreated relapsing or resistant solid tumors (Wilms'--4, rhabdomyosarcoma--3, synovial sarcoma--1) who received 16 courses of chemotherapy: iphosphamide, 1800 mg/m2/day (days 1-5), vepeside, 100 mg/m2/day (days 1-5), and carboplatin 500 mg/m2/day (day 1) (IVC) and 18 courses of therapy wherein iphosphamide was replaced by cyclophosphanum, 400 mg/m2/day (days 1-5) (CVC). The patients received 2-4 induction courses (n = 18) and 1-5 consolidation courses (n = 16) with reinfusion of peripheral stem cells (PSC). All PSC separations were performed after the first or second courses of IVC/CVE. There were no significant increases in the duration of leukopenia and thrombocytopenia, in the incidence of infection with a higher ordinal of a course performed by PSC maintenance. The findings suggest that the small doses of PSC stimulated by colony-stimulating factor can maintain hemopoiesis and decrease the rate of the estimated bone marrow depletion long after repeated courses of chemotherapy in patients with prognostically poor solid tumors.

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.

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.

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 authors discuss the existence of polypotent hemopoietic stem cells in the peripheral blood as well as a possibility of restoring hemopoiesis by means of the given cells after the lethal myelotoxic exposure. In 5 patients with hemoblastoses, suspension of mononuclear leukocytes in an amount of 0.5 X 10(9) per kg bw was obtained using short-interval leukocytapheresis on blood cell separator. After carrying out different schemes of pretransplantation preparation the defrosted suspension of mononuclear cells was injected without wash out to the patients' central vein. The recovery of the peripheral blood indicators was attained on days 10-30 after the autotransplantation of stem blood cells.

The antiserum was obtained from horses immunized with cells from patients with blastic crisis of CML and completely absorbed with normal white blood cells (WBC). The absorbed antiserum remained cytotoxic to blast cells from nearly half of the patients in blastic crisis and did not react with WBC from patients with Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL), Chronic Lymphoid Leukemia (CLL) and Chronic Myeloid Leukemia (CML) in its chronic phase as well as with cells of human normal bone marrow or fetal liver.

The results of experiments carried out to test some of the consequences of the earlier general theory of oncogenesis, according to which the malignant tumor cell can arise as a result of somatic hybridization of cells of different organ- and tissue-specificity, are described. In the first series a tumor induced by cellophane film, was grafted into syngeneic and allogeneic mice, and antilymphocytic serum (ALS) was then injected. Metastases occurred only in allogeneic recipients receiving ALS. It was thus shown that the ability of cells of this particular tumor to metastasize is not a property inherent in its cells but is acquired by them as a result of interaction with the recipient organism. In the second series it was shown by two immunological methods that the cells of metastases arising under these conditions contain tissue compatibility antigens of donor and recipient origin, i. e., that they are somatic hybridsmin the third series skin from individuals of another strain was grafted on to mice and ALS was injected; hepatomas developed in 74% of these mice. The theory is used to explain several phenomena of carcinogenesis not explicable by other theories: the phenotypic nature of cell transformation, the causes and nature of the duration of the latent period of tumor development, the mechanism responsible for the ability of tumors to overcome the system of immunological defense, the mechanism of activation of endogeneous oncogenic viruses, etc. Finally an answer is given to the question: what is a tumor?

Oral administration of deoxycytidine simultaneously with intraperitoneal injections of toxic doses of cytosine arabinosidetomice with advanced L1210 leukemia diminished the toxic effects preventing drug death of these mice. They developed a marked antitumor effect. The mean survival time of these mice was considerably extended as compared to that of untreated animals or those given one of these drugs alone. At the optimum schedule of treatment about 23% of the mice survived over 60 days. Deoxycytidine protection reduced the antileukemic effect of cytosine arabinoside administered in nontoxic doses. The deoxycytidine plus cytosine arabinose combination was ineffective in the treatment of transplantable myeloid leukemia in mice.

Oral administration of deoxycytidine simultaneously with intraperitoneal injections of cytosine arabinoside reduced toxicosis preventing drug death of mice with L1210 leukemia. These animals developed a marked antitumor effect having the median survival time (MST) considerably longer than that of untreated animals or of those receiving either of these drugs alone. At the optimal dose schedule 23% of mice survived 60 days. Under similar conditions mice with myeloid Graffi leukemia showed no antitumor response.