Family with Li-Fraumeni syndrome and no evidence of a germline mutation of the p53 gene or chromosomal aberrations.

Li-Fraumeni syndrome is a rare autosomal, dominant trait of diverse types of cancers in children and young adults, with a predominance of soft tissue sarcomas, osteosarcomas, brain tumours, adrenocortical and breast carcinomas, as well as leukaemias. We present a family with an unusual cancer history fulfilling the criteria of Li-Fraumeni syndrome. Mutational analysis of the p53 gene in constitutional DNA of several affected members of the family did not show any germline p53 defect. Cytogenetic studies did not reveal any structural aberrations.

[Chronic eosinophilic leukemia]. / Przewlekla bialaczka eozynofilowa.

In this research one case of chronic myelogenous eosinophilic leukemia (pbe) transformed into myeloblastic crisis in male patient aged 24, efficiently treated chemotherapy with following performing allogenic bone marrow transplantation was represented. The patients was admitted to the Department of Hematology with the cause of increased leucocytosis (up to 19.9 x 10(9)/l), eosinophilia (up to 15.3 x 10(9)/l), enlarged percentage of eosinophillic granulocytes in bone marrow, splenomegaly, anaemia and thrombocytopenia. Cytogenetic tests did not reveal any chromosomal disturbances, and PCR test did not detect bcr/abl rearanzation. After 7 monthly period of chronic phase of disease there was appeared symptoms of blastic acceleration myelogenous disease i.e. enlargement of splenomegaly, intensification of anaemia and thrombocytopenia, very fast increasing leucocytosis in short time together with presence of myeloblasts in blood and bone marrow smear tests. Blastic acceleration pbe with eosinophils dominant in bone marrow was confirmed by flow cytometry. Induction chemotherapy according to schedule HAR (Hydroxyurea--H, Arabinoside Cytosine--A, Doxorubicin--R), consolidation and irradiation of spleen allowed to receive complete remission. The patients was undergone allogenic bone marrow transplantation (allo-BMT) from related donor (younger brother). The follow-up with the period 18 months after allo-BMT has not revealed the relapse of disease.

[Leukostasis syndrome in a case of chronic lymphocytic leukemia]. / Zespól leukostazy w przebiegu przewleklej bialaczki limfatycznej.

The leukostasis syndrome is rare complication of leukemias with extremely high white cell counts. It occurs most frequently in chronic myelosis or acute leukemias and is exceptional in chronic lymphocytic leukemia (CLL). A severe leukostasis syndrome was observed in a case of CLL with peripheral lymphocyte count of 1,120 G/L. Typical symptoms of respiratory and central nervous system were developed (tachypnoe, hypoxia, headache, slurred speech, somnolence and confusion). Leukapheresis decreased the lymphocyte count to 305 G/l rapidly and reversed the leukostasis syndrome.

Blood plasma pseudouridine in patients with malignant proliferative diseases.

The blood plasma concentration of pseudouridine was estimated in 104 healthy adult subjects, and 108 patients suffering from malignant proliferative diseases. The HPLC method for simultaneous determination of pseudouridine and creatinine was applied. The average physiological concentration of pseudouridine in blood plasma was 2.43 +/- 0.97 mumol.l-1 or 29.15 +/- 7.40 mmol.mol-1 creatinine. The physiological urinary excretion of pseudouridine was 14.32 +/- 5.20 mumol.24 h-1.kg-0.75 or 19.60 +/- 5.22 mmol.mol-1 creatinine. Renal clearance of pseudouridine and endogenous creatinine were 4.04 +/- 0.99 and 5.50 +/- 1.46 ml.kg-0.75, respectively. A positive correlation (r = 0.55, P < 0.01) was found between age (in the range 20-92 years) and blood plasma pseudouridine concentration (mumol.l-1). By expressing plasma pseudouridine in relation to plasma creatinine, the apparent influence of non-metabolic factors (age, renal insufficiency, blood dilution) on the plasma pseudouridine concentration were largely excluded. Among haematological proliferative diseases the highest values of plasma pseudouridine concentrations were observed in chronic lymphocytic leukaemia (8.19 mumol.l-1; 54.9 mmol.mol-1 creatinine) and multiple myeloma (7.02 mumol.l-1; 52.5 mmol.mol-1 creatinine). In multiple myeloma, but not in chronic lymphocytic leukaemia, the plasma pseudouridine concentration depended on the clinical stage. A lower, but still significant response in non-Hodgkin's lymphoma was noted (4.03 mumol.l-1; 40.88 mmol.mol-1 creatinine). A significant increase of the plasma pseudouridine concentration was characteristic of adenocarcinomas of the large intestine, and it occurred in the early stages of malignant growth. In patients with lung cancer the plasma pseudouridine concentration was elevated only in advanced cases with metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of urinary neopterin and pseudouridine in patients with malignant proliferative diseases.

The HPLC method for the simultaneous determination of urinary neopterin, pseudouridine, and creatinine allows a rapid evaluation of the activation state of cell-mediated immunity, and the stimulation of whole-body rRNA + tRNA turnover, associated with malignant growth. Urinary neopterin and pseudouridine concentrations in healthy subjects amounted to: 106.6 +/- 34.6 mumol/mol creatinine, and 19.6 +/- 5.2 mmol/mol creatinine (mean +/- SD), respectively. The increase of neopterin excretion in patients with haematological neoplasms ranged from 146% in Hodgkin's disease to 534% in non-Hodgkin's lymphoma, whereas the increase in cancer cases ranged from 95% in adenocarcinoma of the gaster to 741% in hepatocellular carcinoma. The changes in pseudouridine excretion were much less pronounced: 63% in non-Hodgkin's lymphoma and 120% in carcinoma of the urinary bladder. The correlation coefficient between neopterin and pseudouridine was relatively low (r = 0.43), although statistically significant (P < 0.01). In the case of several neoplasms e.g. Hodgkin's disease, polycythaemia vera, and adenocarcinoma of the gaster, neopterin was significantly elevated, whereas pseudouridine remained at a normal concentration. There was a positive relationship between the stage of the disease (primary focus, regional metastases, dissemination) and urinary concentration of pseudouridine in patients with adenocarcinoma of the large intestine. In the same patients the increase of neopterin excretion was noticed both in early and advanced stages, with the highest values in disseminated disease.

[A case of eosinophilic leukemia]. / Przypadek bialaczki kwasochlonnej.

The clinical course and diagnostic difficulties in a case of eosinophilic leukaemia are described. For a long time period the case showed clinical manifestations of a hypereosinophilia syndrome. Shortly before death clinical signs of leukaemia developed, and the diagnosis was confirmed on autopsy.

Heterogeneity of cytoplasmic and nuclear shape of lymphocytes during progression of chronic lymphocytic leukemia.

Peripheral blood from ten healthy subjects and from 44 patients at stages 0, I, II, III, IV of chronic lymphocytic leukemia (CLL), type B, was routinely smeared, fixed and stained by the May-Grunwald-Giemsa method. Fourier analysis of nuclear and cytoplasmic shape of smeared lymphocytes was carried out for the range 1-20 of harmonics (describing the pattern of contour folding in quantitative terms). In addition the roughness coefficients (describing the summarized measure of contour folding of an individual cell) were calculated and computer evaluated. Cytoplasmic contour shape of smeared lymphocytes in the 6-10 harmonic range discriminates well between lymphocytes of healthy subjects and those of each CLL stage. This discrimination was the result of richer folding of CLL lymphocytes. Nuclear contour shape of lymphocytes in the 6-10 harmonic range fails to discriminate between lymphocytes of healthy subjects and those of CLL, but it discriminates well between lymphocytes of various stages of CLL, with the exception of stages I/II and III/IV. When Fourier analysis was carried out on lymphocytes of combined stages I + II and III + IV, the shape differences were even more accentuated. We conclude that nuclear and cytoplasmic contour shape is a phenotypic feature of lymphocytes that is markedly modified in the course of CLL progression; this feature may be used as a new parameter in CLL.

Analysis of chromatin pattern in blood lymphocytes of healthy donors and in lymphoid cells of patients with chronic lymphocytic leukaemia.

The optical Fourier transformation was used to analyse the chromatin/interchromatin pattern of lymphocytes of healthy subjects and lymphoid cells of patients with chronic lymphocytic leukaemia (CLL, type B, stage O). Peripheral blood smears were prepared routinely, fixed, and stained by the Feulgen method, and the photographic images of the nuclei were quantitatively analysed. From the radial distribution of light intensity of diffractograms, several Feulgen chromatin (F-chromatin/interchromatin) descriptors were evaluated. Four showed the strongest discriminant power and these descriptors discriminated well between lymphocytes of healthy donors and lymphoid cells of CLL patients, although F-chromatin/interchromatin components of the same sizes were found in lymphocytes and lymphoid cells.

Fourier analysis of nuclear and cytoplasmic shape of blood lymphoid cells from healthy donors and chronic lymphocytic leukemia patients.

The folding rates of the contours of nuclei and entire lymphoid cells were analyzed by Fourier analysis of the shapes. Smears of peripheral blood from healthy subjects and from patients with chronic lymphocytic leukemia (CLL: type B, stage zero) were routinely prepared and stained. The shapes of lymphoid cells from CLL patients revealed a higher folding rate (from fifth to tenth harmonics) than did those of lymphocytes from healthy subjects. Accordingly, the roughness coefficient (describing the folding rate of the surface) for CLL cells was 0.036, as compared to 0.028 for the cells of healthy subjects. The shapes of nuclei of CLL lymphoid cells also had a higher folding rate than did those of lymphocytes from healthy subjects, but a significant difference was found only for the highest harmonic calculated (the tenth harmonic); the respective roughness coefficients for nuclei were 0.037 and 0.033.

The double gammopathies. Clinical and immunological studies.

A retrospective review of 1135 patients with paraproteinemias recorded 28 (2.5%) as having two M components. This group included 11 patients with myeloma, 6 with lymphoproliferative disease, 5 with a nonlymphoproliferative malignancy, and 6 with a double gammopathy of undetermined significance. In 13 cases in which the M components were measured over a period of time, three distinct patterns were observed, which may reflect the cellular and subcellular origin of the two proteins: 1) In 2 cases the minor component remained relatively stable while the dominant protein changed with time and treatment, suggesting the origin to be two cell lines--the minor arising from a quiescent clone of the monoclonal gammopathy of undetermined significance, and the major M component arising from a more rapidly proliferating plasma cell line; 2) a discordant pattern was seen in 4 patients, suggesting that the two M components arose from two separate plasma cell clones; 3) seven cases in which the proteins behaved in a concordant manner probably arose from a single plasma cell clone with incomplete class switching, producing two M components with different heavy chains.

Immune condition in patients with Hodgkin's disease.

In 40 cases of Hodgkin's disease (24 untreated patients and 16 patients in remission) the immunological humoral and cell-mediated competence was studied using test of hypersensitivity of DNCB and PPD, blastic transformation and the ability of 3H-DNA synthesis in lymphocytes stimulated with PHA and PWM, and in some cases, with PPD. In all patients the concentration of serum immunoglobulins was determined as well. Impairment of immunological reactivity was found in about 40% of patients, on the average, in various stages of the disease and during remissions following treatment with cytostatic agents and radiotherapy. The most frequent abnormality found in 52.5% of cases was impairment of blastic transformation of lymphocytes stimulated with PHA in vitro. In 60% of cases negative results of intradermal test with PPD and in 75% of patients the DNCB test was negative. No correlation could be found between impairment of the immune competence in this disease and the clinical stage and/or type of histological changes in lymph nodes.

Cell-mediated and humoral types of immunologic immunity in idiopathic pancytopenia.

In a majority of 34 patients (including 30 treated with androgens and glucocorticosteroids), the absolute lymphocyte count, percentage of the T population and its reactivity in vitro to PHA, PWM and sheep erythrocytes were normal. In one fourth of cases, serum levels of IgG and/or IgM classes of immunoglobulins were decreased. The deviations in levels of serum immunoglobulins, and in some patients in the lymphocyte count and in the T population and its reactivity to antigens were attributed to complex causes, including immunosuppressive treatment with adrenal glucocorticosteroids. It is suggested that indications for treatment with these hormones in cases of bone marrow aplasia with suppression of the lymphoid system should be restricted.

[Analysis of 300 cases of secondary pancytopenia]. / Analiza 300 przypadków pancytopenii wtórnych.

Clinical analysis of 300 cases of secondary pancytopenia treated in a period of 10 years is reported. The disease was more frequent in women than in men. The most frequent single cause were drugs, among them chloramphenicol. Most patients had pancytopenia and hypoplastic bone marrow. The mortality was 37%. Death occurred most frequently in the first 6 months of the disease due to infection or thrombocytopenic heamorrhagic diathesis. The results of treatment with corticosteroids and androgenic steroids were unsatisfactory.