E rosettes in lymphoproliferative diseases.

Results are given of investigations of E rosettes in patients with chronic lymphadenosis and malignant lymphoma. The quantity of E rosettes was expressed both as per cents and in absolute numbers calculated from the total amount of lymphocytes in peripheral blood. In the normal controls the percentage of E rosettes was 58% on average while in patients with chronic lymphadenosis it was found to have decreased significantly down to a mean of 6%. However, in absolute values the number of rosette forming lymphocytes was normal and even higher. In the group with malignant lymphoma the percentage decrease was less striking than in those with chronic lymphadenosis, however, the absolute number of rosette forming lymphocytes was always found to be lowered because of evident to considerable lymphopenia. A dynamic study of the observed changes might contribute to a knowledge of the pathophysiology of lymphoproliferative diseases.

Monitoring of residual disease in non-Hodgkin's lymphomas by quantitative PCR (preliminary report).

Highly sensitive PCR techniques are often used in molecular monitoring of hematological malignancies, and a quantification of residual disease is important for further prognosis. Here, the limiting dilution methodology and the multiplex IgH/ras PCR are proposed as approaches to molecular monitoring of NHLs. Applying the limiting dilution methodology as a simple dose-response assay for the translocation t(14,18) and CDR3 clonal rearrangement of IgH, critical amounts of total cells determined with stored consecutive diagnostic samples in the same PCR run are compared. Assuming that specific targets are diluted proportionally in dilution of total genomic DNA, the samples showing lower critical concentrations of total DNA are considered as containing higher portion of cells possessing the specific disease marker and vice versa. So far, the correlation of results with the disease outcome confirmed that this simple semi-quantitative approach may in some cases substitute laborious precisely quantifying techniques in the monitoring of the disease. In optimized multiplex IgH/ras PCR co-amplifying clonal CDR3 rearrangement of IgH and the codon 61 of Hras 1 gene, the amount of CDR3 product as the disease marker is related to the ras product as a standard marker of all cells, and quantitative results are obtained by software analyses of detecting gels. Presumably, both approaches may provide clinically useful information on the disease activity and treatment outcome.

[Familial occurrence of malignant hematologic diseases]. / Familiární výstyt maligních hematologických onemocnení.

The cases of first-degree relatives from five families with hematological malignancies are described in this study. The occurrence of non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphoblastic leukemia (B-CLL) in the first family, NHL and chronic myeloid leukemia (CML) in the second one, two cases of Hodgkin's disease (HD) in the third and the fifth one's NHL and acute myelomonocytic leukemia (AMML) in the fourth one observed. Several factors which are considered to be involved in etiopathogenesis of hematological malignancies (virus infection, immune defects, HL-A antigens, cytogenic features) were discussed. Our study confirm other previous findings, that the familial susceptibility results from a combination of genetic and environmental influences.

[Semiquantitative monitoring of molecular markers in non-Hodgkin's lymphoma]. / Semikvantitativní sledování molekulárních markeru u nehodgkinských lymfomu.

BACKGROUND: As quantitative changes of disease specific molecular markers may reflect disease activity, various methods quantifying targets of polymerase chain reaction were developed and their clinical relevance should be established. METHODS AND RESULTS: Here the exploitation of the DNA limiting dilution methodology in molecular monitoring of non-Hodgkin's lymphomas is presented. Long-term stored diagnostic DNAs are checked for their integrity and examined in dose-response assays for semiquantitative estimates of t(14,18) translocations and clonal immunoglobulin heavy-chain gene rearrangement. Assuming that the specific targets are diluted proportionally by dilution of total genomic DNA, sensitivities of polymerase chain reaction expressed as minimal amounts of total cells in reaction initiating positivity are compared. The term PCR-detectability as the ratio of sensitivities determined for preceding and actual samples is introduced. The value of PCR-detectability lower than one is considered as an indicator of a decrease of cells bearing the marker and vice versa. So far, the considerable increases in PCR-detectabilities were found close to relapses and unsubstantial changes at clinical remissions. CONCLUSIONS: It is presumable, that the semiquantitative limiting dilution approach may contribute to the monitoring of disease and treatment outcome.

[Holter monitoring of patients treated with cytostatic agents]. / Holterovské monitorování nemocných lécených cytostatiky.

After cytostatic treatment severe arrhythmias, the development of angina pectoris and even the development of acute myocardial infarction and sudden death were observed. Therefore we made in 42 patients with malignant haematological disease treated with cytostatics 96 Holter monitorings of the electrocardiographic signal. The monitoring was made during the administration of cytostatics as well as during the time interval between the administration of combinations of cytostatics. In both instances (during the administration and during the interval between administration) we recorded a surprisingly high, mean all-day as well as maximal, heart rate. In the group monitored during administration of chemotherapeutic drugs we observed 5-8 hours after administration of cytostatics serious ventricular arrhythmias [incl. ventricular tachycardia], denivelization of the ST segment, paroxysms of supraventricular tachycardia. In the group monitored during the interval between administration of cytostatics the sick-sinus syndrome was recorded, as well as a passive nodal rhythm, disorders of the intraventricular conduction. The described changes are explained by the release of vasoactive substances after administration of cytostatics, by a change of the transmembrane calcium transport leading to an increased excitability of the heart muscle and possibly to coronary spasms and direct irreversible damage of the conduction system.

[Detection and significance of chromosome abnormalities in patients with malignant non-Hodgkin's lymphoma using the polymerase chain reaction]. / Detekce a význam chromozomálních abnormalit u nemocných s nehodgkinskými maligními lymfomy metodou polymerázové retezové reakce.

BACKGROUND: Morphology and immunological marker analysis are insufficient to detect neoplastic population in some cases (15%) of non-Hodgkin's lymphomas (B-NHL). Aim of the study was to detect malignancy at molecular level using polymerase chain reaction. METHODS AND RESULTS: We examined a diverse set of B-NHL (90 patients--48 men, range 18-76 years, mean age 53 years and 42 women, range 20-86 years, mean age 54 years) to detect immunoglobulin heavy chain (IgH) rearrangement. 32 patients with centroblastic-centrocytic lymphomas (12 men, range 45-64 years, mean age 52 years and 20 women, range 29-85 years, mean age 53 years) were also studied for translocation (14,18). DNA was isolated from lymphatic nodes, bone marrows and peripheral blood. Translocation (14,18) was founded in 38% lymphatic nodes, 36% bone marrows and in 50% of peripheral blood. The detection rate of IgH PCR varied according to the morphologic type of the analyzed lymphoma specimen. A high detection rate (100%) was observed in low-grade lymphoma, while in high-grade lymphoma was in 62%. In bone marrows samples from follicular lymphomas, IgH PCR positivity was observed in 50% cases without leukaemic blood picture and in 64% cases with lymphoma cells in peripheral blood picture. In peripheral blood with bone marrow infiltration, but without the presence of lymphoma cells (morphological assessment) we observed 71% IgH PCR positive samples. In case, when bone marrow and peripheral blood were morphologic negative, we identified 64% positive cases. Using t(14,18) and IgH PCR we detected neoplastic population in 81% follicular lymphomas. CONCLUSIONS: IgH PCR and t(14.18) PCR are convenient additional technology for detection of neoplastic lymphocytes in B-NHL, particularly when morphology and immunological marker analysis are insufficient.

[Hypercalcemia as the first manifestation of bone marrow T-cell lymphoma]. / Hyperkalcémie jako první manifestace drenového T lymfomu.

The authors describe the case of a 20-year-old patient where the first leading symptom was hypercalcaemia. A similar case was not published so far in the Czech literature. The disease took a fulminant course and proved fatal nine days after the first symptoms of the disease. The correct diagnosis was established only by necropsy. The adverse course of the disease could not be influenced by repeated haemodialysis nor by the administration of disodium pamidronate (Aredia) and calcitonin. The authors discuss differential diagnostic problems of hypercalcaemias and the pathogenesis of hypercalcaemia in malignant diseases of the haematopoietic system.

[Administration of granulocyte-macrophage colony growth factors in the treatment of postcytostatic myelosuppresion in oncohematologic patients]. / Pouzití rustového faktoru pro granulocyto-makrofágovou radu v lécbe postcytostatické myelosuprese u onkohematologických nemocných.

BACKGROUND: Growth factors for granulocytic and granulocyte-macrophage series (G-CSF and GM-CSF) in the form of recombinant proteins are used in various leukopenias. The aim of this work was to follow the effect of GM-CSF (Leucomax Sandoz) in myelosuppression after the therapy with cytotoxic drugs. METHOD AND RESULTS: Leucomax was given to 22 patients with oncohematological disease (3 patients with acute lymphoblastic leukemia, 5 patients with various myeloid malignacies, 4 myelomas and 10 patients with non-Hodgkin lymphomas). In comparison to the literary data lower doses of Leucomax were used, it is 150-200 micrograms a day and patient. The length of administration of the growth factor was reduced to the shortest possible time according to the leukocyte count monitoring. Leucomax administration was started when leukocytes dropped below 1.10(9), in patients with severe leukopenias after repeated chemotherapy Leucomax was applied earlier. From 17 patients treated for sufficiently long period of time 70% responded to the GM-CSF application without any serious side-effects. In most cases, with the exception of myeloma, the growth factor was applied for 4-10 days. The leukocyte increase above 3 x 10(9) appeared in 3-8 days after the start of the treatment. CONCLUSIONS: Correctly indicated application of growth factors in postcytostatic myelosuppression is a great contribution to antitumor therapy. According to our experience in most cases 5-7 days of the daily dose of 150-200 micrograms of GM-CSF is sufficient for the stimulation of leukopoiesis. In postherapeutic myelosuppression in acute myeloblastic leukemia the growth factor should be used only as a life saving therapy since it can stimulate the leukemic cell population.

[Toxic manifestations in the treatment of leukemias and malignant lymphomas]. / Toxické projevy lécby leukemií a maligních lymfomu.

Toxic effect of chemotherapy was found in 13 dead patients suffering from myeloic leukaemia, Hodgkin disease and malignant lymphoma during past 18 months. Drugs with known toxicity from various sorts of antineoplastic treatment were administered simultaneously or successively what did not allow to differentiate their effects. Clinical symptomatology of the patients comprised respiratory distress syndrome or heart failure which could not be otherwise explained. Pneumopathies prevailed (10 cases) over isolated cardiomyopathies (3 cases), their concurrence was found in 3 other cases. Pneumopathies were mostly (9 cases) characterized by diffuse alveolar damage, by often bizarre proliferating type II pneumocytes and capillary thrombi. Simultaneous organizing processes (7 cases) in alveoli and bronchioli were present and sometimes combined with interstitial lung fibrosis; a single secondary alveolar lipoproteinosis was combined with intraalveolar organization. Cardiomyopathies were mostly characterized by irregular cardiocyte hypertrophy and focal fibrosis, sometimes by distended and waved or vacuolated cardiocytes. Toxic lesions are reversible as usual and risky treatment modalities found out by pathologist are to be early modified.

[Peripheral T-malignant lymphoma (PTML)]. / Periferní T maligní lymfom (PTML).

Twelve cases representing variants of peripheral T malignant lymphoma were described for the first time in this country. Rosette test and immunocytology were crucial for their identification. Convoluted nuclei were a dominant histologiial feature as well as a voluminous water-clear cytoplasm which kept being surprisingly well demarked. Basic features were analogous to the Far East cases. Nevertheless, hypercalcemia and substantial pulmonary lesion were not observed.

[Ring-cell immunocytoma with polyneuropathy associated with dysgammaglobulinemia and amyloidosis]. / Immunocytom z prstencitých bunek s polyneuropatií pri dysgamaglobulinémii a amyloidóze.

Dysgammaglobulinemia, amyloidosis and generalization of tumour occurred step by step in sensomotoric polyneuropathy complicating a nonspecified malignant lymphoma. The tumor was specified later as a IgM lambda immunocytoma with substantial participation of signet ring cells. Their vacuoles were sometimes multivesicular and did not contain immunoglobulins. Final phase of the disease was characterized by nodular AL amyloidosis expressed especially in the lung, retroperitoneum and nervous system. Amyloidosis was connected with the vessel walls and their surroundings. Possible autoimmune pathogenesis of polyneuropathy as well as of immunocyte vacuolization were discussed.

[Comparison of proliferative activity in malignant lymphomas determined by immunohistologic methods with various antibodies]. / Srovnání proliferacní aktivity maligních lymfomu stanovené imunohistologicky ruznými protilátkami.

Proliferation Index (PI) was evaluated in a group of 48 malignant lymphomas. Comparison of 3 antibodies showed that DAKO-EPOS Anti-PCNA/HRP and MIB-1 (Immunotech) suite to routine PI evaluation. Low figures of PI were obtained when using DAKO-EPOS Anti-Ki-67/HRP which did not even discriminate between prognostic groups of malignant lymphomas.

[The second reading of hematologic biopsies]. / Druhé ctení hematologických biopsií.

Occurrence of differences between the first and the second reading was compared in three time periods. The first from the years 1975-1989 showed disagreement in 34%, the second from 1990-1991 in 86%, the latest from 1994-1995 in 45%. The failures of the same sort repeated in 19 from 42 cases. They could be avoided by confining capacities of one's own department and using advantage of consulting reading by other pathologist. The second reading asked by an oncologist represents an independent urgent part of individual patient's treatment and should be generally supported and freed from any hindrance.

The source and clinical significance of serum alkaline phosphatases in neoplastic blood diseases.

Total serum alkaline phosphatase activity and its isoenzymes were studied in 126 patients sent to hospital with a neoplastic blood disease. They comprised 63 patients with a lymphoreticular neoplastic disease, 17 with immature stem-cell leukaemia, 11 with a plasmocytoma, 16 with lymphocytic leukaemia, 4 with polycythaemia and 9 with the myelofibrosis syndrome. Evaluation of the serum alkaline phosphatase isoenzymes significantly enhances the efficiency of the diagnosis and the organ specificity of the enzymes in these conditions. It is particularly important in the above states for studying liver and bone involvement, both from the aspect of the organic localization of the disease and from the aspect of evaluation of the success of therapy.

[Caplan's syndrome]. / Caplanuv syndrom.

The authors describe two cases suffering from Caplan s syndrome, i.e. a combination of pneumoconiosis and rheumatoid arthritis, in miners of deep coal mines in southern Moravia. The finding on the lungs preceded the manifestation of articular symptoms. The disease progressed even after the risk of fibrogenic dust was eliminated. In both patients occupational diseases were involved.