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We report a case of aceptic osteonecrosis (AON) of the left hymerus epiphysis in programmed treatment of a male patient with lymphoblastic lymphoma to illustrate clinical, laboratory, epidemiological, pathogenetic, diagnostic and therapeutic aspects of AON in programmed therapy of acute lymphoblastic leukemia (ALL). We believe that AON is a rather frequent but often missed for early diagnosis complication of ALL treatment. Even a weak pain in bones and joints under mechanical load in patients on long-term treatment with glucocorticosteroids is an alarming symptom which may indicate a risk of an osteodestructive process and relevant diagnostic and therapeutic measures may be needed.

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AIM: To study morphoimmunological and clinical features of primary mediastinal large B-cell lymphoma (PMLBCL). MATERIAL AND METHODS: We analysed the results of biopsy material study and treatment of 86 PMLBCL patients, effects of different factors on the disease prognosis, efficacy of some therapeutic programs and overall therapeutic efficacy. RESULTS: PMLBCL manifests mainly with massive lesions of anterior upper mediastinum with involvement of adjacent organs and tissues, absence of bone marrow involvement, frequent affection of CNS. Many primary patients have resistance to treatment, sensitive patients have no late recurrences. CONCLUSION: PMLBCL is an independent extranodal variant of non-Hodgkin's lymphoma with special clinical and morphoimmunological characteristics. Criteria are proposed for differential diagnosis of different variants of PMLBCL. New approaches to PMLBSL patients' management are outlined.

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AIM: To study efficacy of velcade therapy in patients with progressive or refractory multiple myeloma (MM). MATERIAL AND METHODS: From April 2005 to November 2006 velcade was used in therapy of 18 patients (11 females and 7 males) with progressive or refractory to prior standard therapy MM course. The patients' age median was 55 years (36 to 76 years). Velcade was injected intravenously on the course days 1, 4, 8 and 11 with interval 10 days between the courses. A total of 77 courses were made (median 4.5). RESULTS: Overall efficacy was assessed according to EBMT criteria in 16 (68%) patients. Partial remission (PR) was achieved in 9 patients, complete remission (CR)--in 1, minimal response (MR)--in 1 patient. Five patients failed the treatment. In 5 of 11 patients with confirmed efficacy of velcade the drug was used in induction of remission before high-dose chemotherapy (HDC) and autotransplantation of hemopoietic stem cells (HSC), in 3--as monotherapy, in 1--in combination with high-dose dexamethasone, in--with high dose dexamethasone and doxorubicin. Four patients achieved PR, one--MR. HSC were obtained before velcade therapy in one patient, in 4--after its conduction. After HDC there were one CR and 4 PR. Recovery of hemopoiesis after HDC took the same time as after standard induction therapy. In 6 of 11 patients HDC was not performed. Velcade therapy is continued in 2 patients, in 1 case with CR the treatment was stopped. In 3 cases PR for 2 to 6 months was followed by the disease progression. CONCLUSION: Velcade as a new effective antitumor drug can be used for treatment of progressive and refractory forms of MM.

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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.

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Clinicomorphological analysis of T-cell-rich B-cell lymphoma in a 50-year-old female and literature data revealed objective difficulties in morphological diagnosis using cytological and histological methods. Large number of epithelioid histiocytes and tumor cells polymorphism resembled Lennert's lymphoma (peripheral T-cell lymphoma). Immunohistochemical study confirmed B-cell origin of tumor cells and large number of reactive T-cells. It is suggested that it would be more correctly to use the term "Lennert-like areas" in such cases with subsequent immunohistochemical study.

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AIM: Review of literature data and original experience with Richter's syndrome. MATERIALS AND METHODS: 250 patients suffering from malignant lymphoproliferative diseases with blood and bone marrow lymphocytosis were observed. 8 (3.2%) of them developed diffuse large-cell lymphoma (criteria and classification of REAL). RESULTS: 5 of the above 8 patients demonstrated spontaneous regression of lymphocytosis. These cases may illustrate transformation (clonal progression) of one morphological variant of malignant non-Hodgkin's lymphoma into another one, more aggressive. For this rare variant of Richter's syndrome running with regression of lymphocytosis the term Richter-Lortolary syndrome is proposed. Lortolary was the first who revealed a decrease of lymphocytosis in Richter's syndrome. The studies of the genome structure, first of all, of immunoglobulin genes show that in Richter-Lortolary syndrome it is easier, to confirm monoclonality of the two tumors (lymphocytic and large-cell) than to reject it. However, the idea of transformation has not been confirmed morphologically yet. CONCLUSION: Development of diffuse large-cell lymphoma in the course of chronic lymphatic tumor does not always indicate terminal state, later stage of tumor progression and poor prognosis.

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The paper presents clinical, hematological, morphological and immunological characteristics of B-cell lymphosarcoma with prolymphocytic-lymphocytic type of leukemization in 50 adult patients (9 females and 41 males aged 29-86 years). In B-cell immunological subvariant of prolymphocytic-lymphocytic leukemization changes in the primary tumor always corresponded to prolymphocytic variant of lymphosarcoma. This distinguishes B-cell lymphosarcomas from previously described T-cellular ones in which the type of eventual leukemic changes did not always correspond to the kind of initial tumor. The presence or absence of prolymphocytes with split nuclei in bone marrow puncture samples was neither of clinical nor of prognostic significance. In leukemization of B-cell prolymphocytic lymphosarcoma from the cells with split nuclei or cells with different configuration of the nuclei, immunological phenotype typical for B-cell chronic lymphoid leukemia did not occur. In prolymphocytic lymphosarcoma from cells with round nuclei one-third of patients had immunological phenotype more typical for B-cell chronic lymphoid leukemia. However, among them were patients with aggressive course with predominant extranodal location of tumor and prolymphocytic type of leukemization. Tumor nodes in B-cell prolymphocytic lymphosarcomas, irrespective of leukemization morphological variant, proved rather resistant to therapy. A complete clinicohematological remission according to the international criteria occurred in 2 of 50 patients, only.

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The authors studied a blast cell immunological phenotype in 50 adults with lymphosarcoma undergoing leukemization following the pattern of acute leukemia. Among the patients there were 12 females and 38 males aged 14-61. Immunological phenotyping of tumor cells was performed using a panel of monoclonal antibodies to T- and B-lymphocyte antigens, to myelomonocytic cells, some nonlinear and activation antigens. T, B and zero variants of blast cells were identified. Occasionally, blast cells carried nonlymphoid antigens and those corresponding to the common lymphosarcoma subvariant. Leukemization in the direction of lymphoblastic leukemia is associated with greater frequency of lymphosarcoma T subvariant (46%). B-cell and zero subvariants occurred in 28% and 20% of the patients, respectively. The number of complete remissions in the group of patients with T-cell subvariant was greater than in the group with B-cell subvariant. The survival in these two groups, however, was almost similar (median up to 8-12 months). Further studies into lymphoblastic leukemization immunophenotyping can help design programs of differentiated polychemotherapy.

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Metabolism of arachidonic acid in neutrophils was studied in vitro in blood samples obtained from 36 patients with Hodgkin's disease of various stage and histology and 32 healthy donors. The basic metabolites were: leucotriene B4, such products of its omega-oxidation as 20-hydroxy-leucotriene B4 (20-OH-LTB4) and 20-carboxy-leucotriene B4 (20-COOH-LTB4), and 5-hydroxyeicosatetraenic acid. Their profile proved identical in patients with Hodgkin's disease and healthy donors. Most patients with Hodgkin's disease showed a decrease in leucotriene B4 and 5-hydroxyeicosatetraenic acid and an increase in the level of omega oxidation of leucotriene B4 as assessed by omega catabolite/leucotriene B4 ratio. The levels of 5-hydroxyeicosatetraenic acid and leucotriene B4 omega-oxidation were found to depend upon histology and stage of Hodgkin's disease. They were nearly normal in patients with stage III, mixed cellular disease, B-symptoms and signs of biologic activity of tumor. A direct correlation was established between the level of leucotriene B4 omega oxidation in neutrophils and that of ceruloplasmin in blood serum of patients with various stages of Hodgkin's disease.

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The authors reported some data on the frequency and spectrum of mycotic infections in 76 adult patients with different types of acute leukemia over the last 3 years. The growth of fungi of various species was noted in 50 (23%) of 213 bacteriological tests, candidomycetes being the most common type. Three patients with aspergillosis were described in detail, in 2 of them intravital diagnosis was established. One of these patients with a complete response received amphotericin B therapy despite the fact that acute leukemia in this case was refractory to therapy. The other patient died of profuse pulmonary hemorrhage. The main nosological types of systemic mycoses, their clinical picture, prevention, therapy and characteristic features in acute leukemias were under consideration.

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The paper is concerned with the development of extramedullary blast infiltrates in Ph-positive chronic myeloid leukemia. Two cases are described. In one case during the blastic phase lasting 27 months, a female patient developed by turn skin leukemids, lesions of the soft tissues in the knee joint, lesions of the stomach, lungs and heart. Administration of the treatment according to the "3 + 7" scheme (an anthracycline antibiotic plus cytosar) and to the TRAMPCOL scheme brought about the reverse development of the infiltrates. In the second case a male patient in the 12th year of the disease developed, in the absence of the blastic phase, massive blast lesions of the lymph nodes of the mediastinum followed by neuroleukemia. The lesions were removed by the treatment according to the ACOP scheme and endolumbal injections of methotrexate and cytosar. Ten months after diagnosing the enlargement of the lymph nodes of the mediastinum the picture of the blood and the bone marrow remained typical of the marked stage of the disease. The authors provide brief data on 27 patients with extramedullary blast infiltrates in the terminal stage of chronic myeloid leukemia together with short reported data.

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The authors describe a female patient with acute lymphoblastic leukemia. After the first chemotherapy cycle according to the VAMP program the patient developed a complete remission. Further on, repeated extramedullary relapses (neuroleukemia, involvement of the mammary gland tissue and lymph nodes of the mesentery) were observed over 7 years, the data of blood and bone marrow analyses being within normal. At the end of the disease the patient developed a relapse with changes in the blood and bone marrow, however the blast cells were sudan and peroxidase-positive i.e. could be classified as myeloblasts.

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