[MALT-lymphomas in Sjogren's disease].

AIM: To develop algorithm of early diagnosis of extranodal lymphoma arising in patients with Sjorgen's disease (SD). MATERIAL AND METHODS: SD diagnosis was made in 457 patients treated in Rheumatology Institute clinic in 1999-2004, 38 (8.3%) females aged 19-82 had lymphoproliferative diseases. MALT-lymphomas were diagnosed in 15 (42.2%) patients. All the patients have undergone morphological, immunomorphological investigations of the salivary glands, postoperative material was analysed in some patients. In addition, the following investigations were made: ultrasonography of the salivary glands, lymph nodes, viscera; scintigraphy; trephine biopsy of the bone marrow; myelograms; CT of the chest, abdomena and brain; tests for monoclonal immunoglobulins in the serum and light chains in urine; biopsy of the parotid gland. Clinical, morphological and immunophenotypical characteristics of MALT-lymphomas were assessed by WHO classification. Lymphoma stages were classified according to Ann Arbor. RESULTS: Parotid glands were affected with MALT-lymphoma most frequently. Predominant were extranodal lymphomas of the parotid submandibular, minor salivary glands of the lip and lacrimal glands of stage I E-II E. Extranodal lymphoma with nodal lesion of stage IV occurred less frequently. Untreated long existing MALT-lymphomas of the parotid glands may transform into B-large cell lymphomas deteriorating SD prognosis. The presence of long-term (> 12 months) massive enlargement of parotid/submandibular salivary and lacrimal glands, massive infiltration, monoclonal immunoglobulins in blood serum and their light chains in the urine predict development of MALT-lymphoma in SD. CONCLUSION: In SD, MALT-lymphomas develop primarily in target organs--salivary and lacrimal glands. SD patients with persistent enlargement of the parotid glands need biopsy for early detection of malignant lymphoproliferation.

[Argyrophilic proteins of nucleolar organizers regions as markers of malignancy grade of anaplastic large-cell lymphoma and Hodgkin's lymphoma]. / Znachenie argirofil'nykh belkov oblastei iadryshkovykh organizatorov kak markerov stepeni zlokachestvennosti anaplasticheskoi krupnokletochnoi limfomy i limfomy Khodzhkina.

Expression of argyrophilic proteins of nucleolar organizers regions (Ag-NOR-proteins) was studied in tumor cells from 17 patients with a classic variant of anaplastic large-cell lymphoma (ALCL) and 22 patients with Hodgkin's lymphoma (HL). Eight cases of p80+ and nine cases of p80-ALCL were studied. HL was represented by 13 cases with lymphoid depletion by a reticular type and 9 cases with nodular sclerosis with a syncytial growth. Ag-NOR-proteins were identified using histochemical method with silver nitrate. The expression of Ag-NOR-proteins in tumor cells of ALCL and HL appeared intensive, being highest in ALCL cells, in p80+ cells of ALCL there was superexpression. The differences in expression of Ag-NOR-proteins point to different proliferative activity and growth of the above variants of ALCL and HL. The test for Ag-NOR-proteins expression can be recommended as an additional tool in differential diagnosis, determination of malignancy grade, assesssment of prognosis and sensitivity to chemotherapy.

[Prognostic implications of mixed monoclonal cryoglobulinemia in Sjogren's disease]. / Prognosticheskoe znachenie smeshannoi monoclonal'noi krioglobulinemii pri bolezni Shegrena.

AIM: To specify the risk of severe systemic manifestations and transformation into malignant lymphoma in Sjogren's disease (SD) patients with monoclonal mixed cryoglobulinemia (MMC). MATERIAL AND METHODS: A prospective study performed in 1985-1990 included 248 SD patients followed up after the initial detection of monoclonal immunoglobulins (Ig) with serum active rheumatoid factor (RF). The patients' cryoglobulins (CG) were examined. The type of CG was determined by electrophoresis in agarose gel combined with immunofixation and immunoelectrophoresis with mono-specific antisera to heavy and light Ig chains. Biopsies of the lower lip salivary glands and skin were made in all the patients with MMC and 40 patients without CG. The biopsies were studied histologically, histochemically and immunomorphologically. Clinical symptoms and prognosis were studied in all the patients observed in 1985-2000 after the initial diagnosis of MMC. In suspected lymphoma development, histological and immunophenotypical studies of lymph node, bone marrow biopsies, trephine biopsies were made as well as myelograms, Ga-67 scintigraphy, CT of the thoracic and abdominal cavities. The total of clinical, morphological, immunophenotypical and cytogenetic characteristics of lymphoma was estimated by REAL classification. RESULTS: CG at first examination was detected in 50 (20.2%) of 248 patients with SD. 20 (40%) of 50 patients were diagnosed to have MMC with monoclonal IgMchi (19) and IgA (1) in the serum with RF activity. Ten (50%) patients with MMC developed lymphoma after 10.9 +/- 3.3 years, on the average. In the absence of CG lymphoma developed in 5.5% (p < 0.001). B-cell intoxication in patients with diffuse lymphadenopathy, foci of lymphoid infiltration in the lungs, ulcers of the crus and such indices as stab neutrophilic shift, monocytosis, hypoproteinemia with hypogammaglobulinemia, disappearance of the RF, CG, low CIC level, immunodeficiency of monoclonal Ig and appearance of the protein BJ in the urine are markers of developing large B-cell immunosecreting lymphomas. Highly aggressive diffuse LCL resulted in death of 70% SD patients with MMC; 30% died of immunocomplex cryoglobulinemic vasculitis. 10-15-year survival of SD patients after detection of MMC was 50%, free of CG - 97% (p < 0.001). CONCLUSION: MMC is a definite serological marker of developing lymphoma and ulcerative-necrotic vasculitis in SD. In detection of MMC in SD patients it is necessary to prescribe early pathogenetically validated treatment before development of life threatening manifestations.

CD95 (FAS/APO-1) antigen is a new prognostic marker of blast cells of acute lymphoblastic leukaemia patients.

We analyzed CD95(Fas/APO-1) antigen expression on bone marrow blasts in 38 children with acute lymphoblastic leukemia (ALL) receiving a treatment in the Department of Leukaemias at the Cancer Research Center in 1987-1989 years (n = 22) and in 1994-1997 years (n = 16). CD95 antigen expression was studied by monoclonal antibodies (MoAbs) IPO-4 in indirect immunofluorescence analysis. CD95 antigen was expressed on 35.8 +/- 7.5% bone marrow blasts, most frequently (63.6%) in the clinically favourable Pre-B ALL. Only in this group CD95 antigen expression was correlated with CD10 antigen expression that has a positive influence to the time of complete remission in ALL patients. Our data showed that CD95 expression on blast cells is a favourable prognostic sign, associated with increased relapse-free and total survival. On the contrary, the absence of CD95 antigen on blasts is an unfavourable sign for disease evolution.

[Diagnostic criteria and prognosis of mediastinal lesions in children with lymphosarcoma]. / Kriterii diagnostiki i prognoza pri porazhenii sredosteniia u detei, bol'nykh limfosarkomoi.

Treatment for mediastinal lymphosarcoma was given to 71 patients, aged 3-14 years, at the Institute's Clinics during 1982-1991. In that group, there were more males than females (3.4:1), mean duration of the condition of 3 months, T-cell immunity pattern (89.9%), enlarged anterior mediastinal lymph nodes and thymus, pleural lesions including pleuritis, mean mediastinal-thoracic index of 0.5, compression syndrome, elevated concentration of lactate dehydrogenase and presence of tumor cells in the bone marrow and peripheral blood. Among major negative factors of prognosis were inadequate therapy, pleural lesions and stage IV tumor.

[The prolymphocytic-lymphocytic leukemization of B-cell lymphosarcomas]. / Prolimfotsitarno-limfotsitarnaia leikemizatsiia B-kletochnykh limfosarkom.

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.

[A comparative clinico-morphological analysis of acute myelo- and myelomonoblastic leukemias in children and adults]. / Sravnitel'nyi kliniko-morfologicheskii analiz ostrogo mielo- i mielomonoblastnogo leikozov u detei i vzroslykh.

Previous morphocytochemical, immunological and cytogenetic analyses of blast cells in 174 children and 188 adults admitted to Cancer Research Center have shown that compared to adults in children leukemic precursors belong to earlier stage of differentiation similar to polypotent cell. The analysis covered 2 FAB-variants of ANLL comparable by the number of patients and intensity of the given chemotherapy (M2 and M4 ANLL FAB variants). The study included 65 children (50 with M2 and 15 with M4 FAB variants) and 43 adults (26 with M2 and 17 with M4 FAB variants) given therapy of standard intensity in the regimen 3+7 and 2+5. The children more frequently demonstrated involvement of the liver, spleen and peripheral lymph nodes. The percentage of complete remissions in both groups was not significantly different. 2- and 3-year recurrence-free survival was similar in two age groups with M2 FAB variants of ANLL. However, in M4 variant in adults this survival made up 18% against 0% in children. The differences may arise from lower peroxidase activity in children than in adults. It is suggested that M4 FAB variant in adults may indicate better prognosis than in children. Therefore, therapy in children with M4 FAB ANLL variant should be intensified.

[Variants of the interaction of the human T-cell leukemia virus (HTLV-I) with the B-cells of lymphoblastoid lines]. / Varianty vzaimodeistviia virusa T-kletochnogo leikoza cheloveka (HTLV-I) s B-kletkami limfoblastoidnykh linii.

B-cell lymphoblastoid lines which are known to be derived by in vitro inoculation of B-lymphocytes with Epstein-Barr herpes virus (EBV) were shown to be infected with HTLV-1. Three possible variants of HTLV-1 interaction with cells were demonstrated by immunoblot, polymerase chain reaction, and virus isolation: (1) prolonged productive infection; (2) infection of the cells manifested only by the presence of "silent" virus sequences; (3) temporary production of HTLV-1 (3.5 months) after the end of which genetic material persisted in the cells. The long-term productive HTLV-1 infection in EBV-infected B-cells was found to influence the functioning of EBV genome which was manifested by expression of two additional proteins of EBNA-5 group and by changes in the intensity and pattern of LMP and EBNA-2 proteins the functioning of which is associated with immortalizing and transforming properties of EBV.

[Immunogenetic prognosis of the effectiveness of cytostatic therapy of rheumatoid arthritis]. / Immunogeneticheskoe prognosirovanie éffektivnosti ysitostaticheskoi terapii revmatoidnogo artrita.

The time course of in vitro cellular immune reactions by using cyclophosphane, prospidin , and methotrexate was examined in 39 patients with rheumatoid arthritis to make predictions of the efficacy of its cytostatic therapy. The agents were evaluated for effects on the expression of Ia-like antigens on the peripheral lymphocytes and synovial fluid of the patients. The optimal doses of the agents for this testing had been chosen in the lymphoid cells from MRL31 lpr mice. The active dosage forms of the cytostatics for the experiment were obtained by administering native agents into the retrobulbar plexus of Balb/c mice, followed by blood isolation of active metabolites . The Ia-like antigen pre-expression index which is the ratio of the proportion of Ia-positive lymphocytes in control cultures to that of the cells in the culture after drug addition was used as a marker of the baseline cellular immunity in the patients. The patients having the index more than 1.5 were considered to be sensitive, those with less than 1.5 were insensitive to the drug. Thus, the Ia-like antigen pre-expression index may be used as a predictor in the assessment of the expediency of prospidine use.

[Immunoglobulin therapy of rheumatoid arthritis]. / Immunoglobulinovaia terapiia revmatoidnogo artrita.

The authors studied the effect of the Soviet-made immunoglobulin drug intended for intramuscular administration on the clinico-immunological indices of 15 patients with rheumatoid arthritis (RA). The drug was administered in a dose of 1500-1800 mg for 7 days running of each month. The control group included 15 patients with RA who received the drug in extremely low doses in accordance with the same pattern. Significant positive changes in the majority of the clinico-laboratory indices were noted in the main group. Individual assessment of the drug efficacy allowed one to note improvement in 8 patients (out of 14) in one month, in 7 (out of 12) in 3 months, in 4 (out of 7) in 6 months. One patient exhibited considerable improvement of her state and one developed fever due to which the treatment was discontinued. The results of the therapy correlated with deexpression of Ia-antigens under the effect of the drug on the peripheral blood lymphocytes.

[Monoclonal antibodies to the antigen of myeloid cells]. / Monoklonal'nye antitela k antigenu mieloidnykh kletok.

ICO-G-2 hybridoma clone was obtained after fusion of spleen cells from BALB/c mice immunized with cells from a patient with acute myelomonoblastic leukemia (AMML) and P3 X 63 Ag8.653 cells, using 50% polyethyleneglycol, molecular weight 1500 KD. The antigen with a molecular weight of 100 KD was present only on polymorphonuclear neutrophils and eosinophils of the peripheral blood. The antigen expression was also found on the majority of myeloid precursors and some nuclear erythroid cells. CFU-GM did not express the antigen. Monoclonal antibodies ICO-G-2 reacted with blast cells of some patients with AML, AMML and CML. The antibodies did not react with cells from patients with AMonL, CMonL, ALL, CLL and LSA. Such pattern of reactivity makes these monoclonal antibodies useful for the differential diagnosis of acute nonlymphocytic leukemias and CML in blast crisis.

[IKO-GM-1 monoclonal antibodies in the diagnosis of acute nonlymphoblastic leukemias]. / Monoklonal'nye antitela IKO-GM-1 v diagnostike ostrykh nelimfoblastnykh leikozov.

The paper deals with the analysis of the phenotype of blastic cells obtained from patients suffering various subtypes (FAB-classification) of acute nonlymphoblastic leukemia. The study used monoclonal IKO-GM-1 antibodies complementary to an antigen common to myeloid and macrophagal cells. Also, previously described monoclonal IKO-11, IKO-1, IKO-02 and IKO-10 antibodies were employed. Application of the above antibodies appeared to provide information necessary for differentiating between myeloblastic and monoblastic leukemia. Complex immunologic and cytochemical investigations are required for identifying leukemia subtypes.