[A case of unclassifiable peripheral T-cell lymphoma].
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Biomedical subjects
Publications and source records attributed to R S Samoĭlova.
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AIM: Determination of the importance of serum cytokines (sCD30, sIL-2R, IL-10, IL-6) for diagnosis, response to chemotherapy and remission in patients with lymphogranulomatosis and lymphosarcoma. MATERIAL AND METHODS: Cytokine concentrations were measured in 87 samples of serum (plasma) from 54 patients by ELISA. Diagnosis of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) was made histologically in 24 and 30 patients, respectively. RESULTS: The threshold concentrations of sCD30 (and less specific sIL-2R) for HD and NHL patients allowed to estimate sensitivity to chemotherapy after the second course. The threshold concentration of IL-10 can distinguish HD from NHL. Changes in IL-6 concentrations were nonspecific. CONCLUSION: On the basis of the threshold concentrations of sCD30 and IL-10 we offer the scheme of lymphoma diagnosis and prediction of the disease sensitivity to chemotherapy which reduce the duration of lymphoma restaging.
AIM: To compare forms of chronic lymphoid leukemia (CLL) regarding mutational status of immunoglobulin variable genes. MATERIAL AND METHODS: We have compared clinical, prognostic and immunophenotypic data obtained on 25 cases with different mutational status of IgV genes. There were 10 patients in the mutated group (median age 49.2 years, male to female ratio = 7:3), and 15 patients in unmutated group (median age 46.5, M:F = 13:2). RESULTS: Statistically significant differences were noted in overall survival and CD38 expression. 5-year overall survival in unmutated group was 35%, in mutated group 80% (p = 0.07). In unmutated group CD38 was expressed on more than 50% of cells in 7 out of 14 patients, while in the mutated group in 0 of 8 patients (p = 0.007). We noted high frequency of VH1-69 gene usage in unmutated group (7 of 15 patients), while in mutated group it was used in only 1 case of 10. CONCLUSION: We confirm the differences between groups of CLL with different mutational status of IgV genes. Highly restricted usage of VH-genes and CD38 expression possibly suggest that unmutated group also arises from antigen driven cells.
AIM: To try effectiveness of fludarabine monotherapy in verified chronic lymphoid leukemia (CLL) in pretreated patients. MATERIAL AND METHODS: The treatment effectiveness according to the international criteria of complete and partial remission was assessed in 37 patients with progressive, splenic, tumor and bone marrow forms of CLL given 5-day courses of fludarabine in a single daily dose 25 mg. RESULTS: In progressive CLL, the remission was achieved in 45% of the patients (10% complete and 35% partial), in splenic form--62.5% (12.5% complete, 50% partial), in tumor form--50% (100% partial). In bone marrow form no remissions were obtained. CONCLUSION: Fludarabine is effective in therapy of pretreated CLL patients. The treatment should be adjusted to CLL form.
According to the classification of chronic lymphocytic leukemia (CLL) proposed by A. I. Vorob'ev and M. D. Brilliant in 1983, benign CLL is a distinct form of CLL which is characterized by low level of absolute lymphocytosis, absent or mild peripheral lymphadenopathy, slow progression. No specific therapy is needed. The paper presents clinical, morphological and immunological analysis of 34 cases of benign CLL (17 males and 17 females, mean age 58 years). Patients were included in the study if they had lymphocyte count less than 30,000 and no significant growth of lymphoid tissue for at least 3 years. They were followed up from 3 to 24 years (11 years, on the average). The main features of benign CLL are the following: no "B" symptoms, no essential enlargement of the lymphoid organs, a stable low level of absolute lymphocytosis, low prolymphocyte count in the blood smear (0.95% +/- 0.2), nodular or nodular-interstitial proliferation in the bone marrow. We failed to find any cases with paraprotein secretion. There was immunophenotype typical for CLL in 91% of cases (CD19+, CD20+, CD23+, CD5+, EM+, CR1-/CR2+, sIg+(-)). None was positive for CD38 activation marker. One trisomy 12 cases was detected by FISH method. 8 patients died so far, but not because of the tumor progression or transformation, median survival was 22 years.
The paper presents new findings in favor of recognition of splenic lymphocytoma (SLC). This disease was characterized by A. I. Vorob'ev and M. D. Brilliant in 1982 in terms of detailed clinicomorphological features, prognosis and optimal treatment policy. The study included 52 patients (mean age 53 years) of which 36 were females and 16 males. They were followed up for 5.7 years, on the average. SLC manifested clinically by splenomegaly with minimally enlarged lymph nodes, morphologically by nodular lymphocytic proliferates in the spleen, bone marrow and liver, diffuse or diffuse-nodular proliferation in the lymph node. Peripheral blood contained middle-size lymphoid cells with round nuclei. SLC immunophenotype exhibits moderate or marked expression of CD22 and membrane immunoglobulins, the absence of CD5, CD23 and EM receptor, combination of CR1-/ CR2+. Paraprotein secretion was recorded in 49% of cases. There were frequent autoimmune reactions, especially against erythroid cells and platelets (42%). Optimal therapeutic policy is expectation and eventual splenectomy producing a persistent clinical effect in 94% of patients. In progressive disease long-term therapy with cyclophosphamide is recommended. Thus, SLC is a mature-cell lymphatic tumor growing as a rule in the spleen. Its prognosis in valid therapy is favourable.
The analysis of 67 cases of benign, progressive, tumor CLL, lymph node lymphocytoma, CLL sarcoma transformation showed that the cases were misdiagnosed in 35.8% cases. The most common mistake (25.4%) was aggressive chemotherapy based on histological diagnosis of prolymphocytic, prolymphocytic-lymphoblastic lymphosarcoma without consideration of cytological and clinical evidence, tumor phenotype. The authors think valid to use the following criteria in diagnosis of lymphoproliferative diseases: histological findings, clinical manifestations and blood picture, tumor cell cytology, primary location and predominant dissemination of the tumor, immunophenotype, characteristic chromosomal disorders, response to treatment.
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Immunological and biochemical study of lymphoid cells obtained from 20 patients with various forms of lymphoproliferative disorders has been carried out. It was found that different phenotypes of lymphoid cells at various stages of differentiation have different activity levels of dipeptidyl aminopeptidase IV (DAP IV), plasminogen activator (urokinase type) and cathepsins B + L. The highest proteinase activity values were found in the lysates of just those leukemic T-cells whose phenotypes corresponded to the initial stages of thymic differentiation or to activated T-cells. The 10 times lowered activity was found in the cell phenotypes of mature T-helpers and T-suppressors, and the activity of the both was at virtually the same level. In lymphoid cells of the B-lineage (from pre-B to mature B-lymphocytes) the proteinase activities did not differ essentially: they were 2 to 3 times lower than in the lymphoid progenitors. It was suggested that the regulated activity changes in some proteinases occur during differentiation along the T- or B-pathways. It is likely that the increases in DAP IV and cathepsins B + L activities are associated with the activation of mature lymphoid T- and B-cells. No direct correlation was found between the activity of either proteinase and the expression of any of the surface markers under study.
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Histological and cytological preparations of the lymph nodes, spleen, bone marrow and other tumors from 140 patients with different variants of lymphosarcomas were subjected to a comparative clinicomorphological analysis. The data obtained were correlated to the WHO classification and the working formulation of non-Hodgkin's lymphomas intended for clinical use. It has been found desirable that the working formulation may be used for predicting the disease course and elaboration of the programs of lymphosarcoma treatment.
The activities of seven glycosidases (six lysosomal and one cytosolic) were determined in B- and T-lymphoid cells differing by immunological phenotypes and occurring at various differentiation stages. The cells were isolated from the circulating blood, bone marrow or spleens of patients with various forms of lymphoproliferative disorders. The glycosidase activities varied significantly depending on the phenotype. The highest activity of all glycosidases was observed in cells with a common lymphoid cell progenitor phenotype. In cells having the phenotype of mature T- and B-cells the glycosidase activities were comparatively low. The changes in all glycosidase activities depending on the phenotype and differentiation stage usually occurred in the same direction; however, the degree of elevation or decline of activities of individual glycosidases was different. The activities of N-acetyl-beta-D-hexosaminidase and alpha-D-mannosidase changed dramatically, whereas the changes in the activity of cytosolic neutral alpha-D-glucosidase were less apparent. These data suggest that lysosomal glycosidases play specific roles in lymphoid cell differentiation.
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DAP-IV activity (Gly-Pro-MCA hydrolysis, pH 7.8) was found in lysates of peripheral blood lymphocytes of patients with T- and B-cell forms of malignant lymphoproliferative diseases. The highest DAP-IV activity was seen in the cells of patients with a rare variant of T-cell lymphocytic leukemia (T-CLL); these cells expressed simultaneously the antigens of T helpers and T suppressors (Th and Ts) (OKT4+ and OKT8+). The DAP-IV activity about ten times less was found in the pathological cells with a phenotype of mature Th (Sezary disease), as well as in the cells expressing antigens of both Ts and natural killers (a rare variant of T-CLL). The same activity was also found in Ts (T gamma-lymphocytosis). The data obtained show that the differences in DAP-IV expression are connected with the differentiation step rather than with the belonging to a particular subpopulation of T-cells. DAP-IV activity, which was somewhat lower than that of T-cells, was found in B-lymphocytes of patients with B-CLL, hair-cellular leukemia, and non-Hodgkin's lymphoma. No correlation of DAP-IV activity with the level of E-cellular differentiation was observed.
Interphase lymphoid nucleoli of Ag-NOR stained site areas were measured on the TAS system in peripheral blood lymphoid cells with the known immunologic phenotype of 19 patients with lymphoid neoplasia (non-Hidgkin's lymphoma, CLL, hair-cell leukemia) and 10 healthy donors. The area of Ag-granules in neoplastic cells is much greater than in normal lymphocytes and does not correlate with a proliferation of cells but correlates with a malignancy grade of the disease. These data are discussed in terms of rDNA transcription patterns in malignant cells.
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