[Current diagnosis of acute leukemia (lecture)].
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Biomedical subjects
Publications and source records attributed to M A Frenkel'.
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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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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.
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Megakaryocytic dysplasia, platelet and megakaryocytic counts were measured in 87 ANLL patients. High megakaryocytic levels were registered in 16.1%, normal in 17.2%, low or negligible in the rest of the examinees. Half of the patients had dysplasia. Thrombocytopenia present in 93% of cases attested to ineffective proliferation of megakaryocytes. Increased number of megakaryocytes with signs of dysplasia occurred more commonly in M0- and M4- variants of ANLL universally in anomalies of chromosome 3 long arm with involvement of q21 and/or q26 segments and occasionally in combination with other chromosome disorders. Megakaryocytosis developed less frequently in patients with ANLL variant M2 with t (8;21) and did not correlate with granulocyte and erythroid cell dysplasia. Pronounced megakaryocytosis in combination with thrombocytosis emerged in 4 patients: 2 of them had typical anomalies of chromosome 3--inv3(q21q26) and dup (3q21q26), 1 had monosomy 7 and 1 normal karyotype. Potential mechanisms responsible for dysplasia of megakaryocytes in ANLL are considered.
The paper presents a detailed clinical, hematological, morphological, ultrastructural and immunological characterisation of T-cell lymphosarcoma with prolymphocytic-lymphocytic leukemic transformation (PLLT). In PLLT the proportion of T-cell immunological subvariant of lymphosarcoma came to 15% being detected only in 8 out of 52 examinees. The patients (6 males and 2 females) varied in age from 24 to 76 years (median 49 years) and had the following histological forms of primary tumor tissue: lymphoblastic lymphosarcoma (n = 3), pleiomorphic small cell lymphosarcoma (n = 1), large-cell anaplastic lymphosarcoma (n = 1), prolymphocytic lymphosarcoma. Immunological characteristics of these 8 cases were heterogeneous: in lymphoblastic variant there was immature T-immunological phenotype. In pleomorphic small-cell lymphosarcoma there were also signs of T-cell activation. In large-cell anaplastic lymphosarcoma an immunological phenotype of lymphoid cells from the primary tumor tissue and bone marrow differed in more advanced immunological differentiation of bone marrow tumor cells. In prolymphocytic variant tumor cells had features of T-helpers or T-suppressors. Most of the patients received polychemotherapy according to the schemes for high-grade lymphosarcomas despite PLLT though the latter is not a universal indicator of late tumor progression, more aggressive course of the disease and poor prognosis.
Bone marrow hairy cells were examined in 36 patients with hairy cell leukemia. Cytograms per 100 of hairy cells were assessed in all the patients. Leukemic cell size, cytoplasm profile, shape of the nucleus, and share of granular cells were under study. Cytochemical examination of hairy cells was carried out in 26 patients. Acid phosphatase and its tartrate inhibition, nonspecific alpha-naphthylacetate esterase, acid nonspecific esterase, and PAS reaction were investigated. In 15 patients hairy cells were immunologically examined using immunocytochemical APAAP method with IKO monoclonal antibodies 1, 91, 20, 124, 115, 92, 105, 30, 31, 86, 80, 87, GM-1. Morphologically two types of hairy cells were detectable: typical, with torn villose cytoplasm with numerous processes, and cells with clearly shaped scalloped cytoplasm. The two types did not differ by nuclear shape or size, presence of granules, but differed by their functions. Process hairy cells were characterized by features most typical of these cells: presence of tartrate-resistant acid phosphatase and CD22 (IKO91) B-cellular marker in the phenotype. In scalloped hairy cells cytochemical and immunological signs were less manifest.
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.
Gene engineering interferon made in Russia (reaferon, realdiron) was given to 40 patients with hairy-cell leukemia. Complete and partial remissions were achieved in 56% and 28% of the patients, respectively. Minimum effect was reported in 3% of the cases. In 5 cases with primary resistance or recurrences the authors used pentostatin which produced complete remissions in all the five patients.
The paper presents the results of the retrospective study of blast cells from 377 patients with acute nonlymphoblastic leukemia (ANLL). Morphocytochemical, immunological, cytogenetic assessments and cloning in semisolid agar were employed. The authors specify blast characteristics with reference to ANLL variants according to the FAB classification, define diagnostic criteria for poorly differentiated myeloblastic (MO), erythroblastic (M6) and megakaryoblastic (M7) leukemia, hybrid variants.
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Results of the treatment of 30 adult patients with acute lymphoblastic leukemia are analyzed. Before the treatment was commenced, the patients were distributed into groups with a favourable, intermediate and unfavourable prognosis depending on the signs previously defined by the authors. In the phase of induction and consolidation of a remission, the treatment intensity in these groups varied. The rate of complete remissions (CR) reached 70% in the whole group; provided Ph-positive ALLs were excluded from the analysis, it was 75%, the median duration of the CR amounted to 21 months, the projected 4-year relapse-free survival was 41%. In the group of historic control (31 patients treated in accordance with the unified program), these indicators were 58 and 69%, 18 months, and 21%, respectively. All the differences appeared statistically insignificant. In spite of the total treatment intensification, the rate of lethal outcomes did not rise during remission induction.
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This method (PAP method) may be used for determining the cellular immunologic phenotype in bone marrow and blood smears, of the blast elements in hemoblastosis patients among other things. The panels of monoclonal antibodies for the PAP method should be selected by their preliminary testing in the PAP method and in immunofluorescence test. PAP method with monoclonal antibodies may be used in both hematologic and cytologic laboratories for determining the histogenetic appurtenance of the cells in dubious diagnostic cases.