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Biomedical subjects

P Zák

Publications and source records attributed to P Zák.

At least 19 recordsLinked to original sources
PubMed2007

Is FLT3 internal tandem duplication significant indicator for allogeneic transplantation in acute myeloid leukemia? An analysis of patients from the Czech Acute Leukemia Clinical Register (ALERT).

To assess the prognostic relevance of activating mutations of FLT3 gene on outcome of allogeneic transplantations in AML patients, we performed an analysis of all patients with FLT3 mutations registered in the Czech Acute Leukemia Clinical Register (ALERT) from 2003 till the end of 2005. Within the mentioned period 170 patients with AML of median age 56 years (23-77) were investigated for FLT3 mutation, within them 36 cases (21%) with FLT3 mutations (32 FLT3 ITD and 4 FLT3 D835) were found. Out of FLT3 ITD positive patients 13 had allogeneic transplantation, 20 patients with mutations of FLT3 were treated with chemotherapy without transplantation. Results of the treatment of these patients were compared with the results of the group of patients without FLT3 mutation, which was according to other characteristics identical with the group of patients with FLT3 mutations (n=134). Median overall survival (OS) was significantly shorter for patients with FLT3 ITD (34.8 weeks) than for those without FLT3 mutations (67.7 weeks; P=0.028). Median OS of patients with FLT3 ITD who had allogeneic transplantation was 42.5 weeks; median OS of patients with FLT3 ITD treated only with chemotherapy was 29.6 weeks (P=0.362). After allogeneic transplantation, median OS of FLT3 mutations negative patients was similar to FLT3 ITD positive patients (46.7 versus 42.5 weeks; P=0.443). Our results suggest that at present there is no strong evidence that FLT3 status alone should influence the decision to proceed to allogeneic transplantation in AML patients. Decision to proceed to alogeneic transplantation should not be based on the FLT3 status only, but it should also consider other prognostic factors.

Acute Disease↗
PubMed2006

[Risky medication and contrast media-induced nephropathy in patients with diabetes and hypertension].

Contrast media-induced nephropathy (CMIN) is accompanied by high morbidity, lengthy hospitalization, and a higher mortality rate. In proportion to the rising number of diagnostic and interventional radiological procedures, the prevalence of this complication is also rising The study briefly tackles the currently known pathophysiological mechanisms that lead to CMIN and deals with various risk factors which increase the probability of development of contrast nephropathy. Among these factors are, in the first place, diabetes mellitus, a pre-existing renal illness and hypertension. In addition, the risk of developing CMIN significantly increases in patients on risky medication. In our study, this medication was a combination of ACE-inhibitors (ACEI) and furosemide. Even though none of the patients met the criteria defined for CMIN, radiocontrast examination showed a significant statistical decline in glomerular filtration (GFR) and a rise in proteinuria (PU) in the sub-group which used this combination of medication. The risk level of this medication especially in patients with pre-existing nephropathy is also underlined by the suggested dependency of the relative rise in the serum levels of creatinine in terms of its input value. It is necessary, as early as the radiocontrast examination is being done, to bare in mind the possibility of CMIN occurring and avoid it also through the modification of the risk factors which can be influenced, e.g. elimination of risky medication and in indicated cases, taking preventive measures.

Aged↗
PubMed2005

The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.

Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.

Acute Disease↗
PubMed2004

Effect of 2-chlorodeoxyadenosine therapy on bone marrow fibrosis in hairy cell leukemia.

The study shows the influence of 2-chlorodeoxyadenosine therapy on bone marrow fibrosis in patients with hairy cell leukemia. Eighteen patients were studied; bone marrow fibrosis was graded 0-4 according to the quantity and pattern of distribution of reticulin. The grade of bone marrow fibrosis was established before the therapy and then in 12- and 24-month intervals. Patients showed complete remission after the therapy and remarkable reduction of bone marrow fibrosis.

Adult↗
PubMed2004

[Importance of immunophenotyping in the diagnosis of B-cell lymphoproliferative diseases ].

The immunophenotyping of the lymphoproliferative diseases is considered to be an integral part of the diagnostic process pointing to the correct classification of the individual diseases and to the choice of the most suitable type of therapy. This article describes the immunophenotype of particular types of B-lymphoproliferative disorders included in the World Health Organization classification (WHO) and the prognostic importance of some markers. The panel of specific monoclonal antibodies directed to B-cell lineage used in our department is displayed.

B-Lymphocyte Subsets↗
PubMed2004

[Bone marrow fibrosis during therapy of hairy cell leukemia].

The influence of Cladribin therapy to bone marrow fibrosis in patients with hairy cell leukemia was studied. Eighteen patients were included in the study; bone marrow fibrosis was graded 0-4 according to the quantity and pattern of distribution of reticulin. The grade of bone marrow fibrosis was established before the therapy and then in 12- and 24-month intervals. Patients showed complete remission after the therapy and remarkable reduction of bone marrow fibrosis.

Aged↗
PubMed2004

[Complete regression of bone marrow fibrosis following allogeneic peripheral blood stem cell transplantation in a patient with idiopathic myelofibrosis].

The authors present a case of a 47-year-old man with idiopathic myelofibrosis. The diagnosis of myelofibrosis was made in 1981. Because of progression of the disease and failure of hematopoiesis in 2002, allogeneic peripheral blood stem cell transplantation was performed; the donor was an HLA identical relative. Six months after transplantation, trephin biopsies were made and a complete regression of bone marrow fibrosis was documented. It is the first case of this treatment for idiopathic myelofibrosis in the University Hospital in Hradec Králové.

Adult↗
PubMed2003

[Immunohistochemical detection and quantification of minimal residual disease using DBA.44 antibodies in trephination biopsies of hairy cell leukemia].

Hairy cell leukemia patients treated with 2-chlorodeoxyadenosine or 2-deoxycoformicin achieve a very high number of therapeutic responses. After complete remission, i.e. minimal residual disease, we cannot demonstrate the disease activity, splenomegaly, or lymphadenopathy; moreover, there comes to normalization of hemoglobin concentration, leukocyte count, and platelet count. No leukemic cells in peripheral blood or bone marrow smears can be seen with the use of staining techniques. They can be demonstrated immunohistochemically in decalcified trephine bone marrow biopsies with the use of DBA.44 antibody together with their morphologic features. For quantification of leukemic cells we use LUCIA-M image analysis.

Antibodies, Monoclonal↗
PubMed2002

[Hairy-cell leukemia].

Presented is on overview of hairy cell leukemia problems in diagnostics. Methods of diagnosis--both clinical (clinical course, laboratory findings) and histopathologic are described in detail. There are also immunophenotypic findings described. Furthermore, differential diagnosis together with therapeutic methods, and the prognosis of the disease are depicted, too.

Diagnosis, Differential↗
PubMed2001

Case report. Disseminated infection of Blastoschizomyces capitatus in a patient with acute myelocytic leukaemia.

Blastoschizomyces capitatus infection in a 48-year-old man with acute myelocytic leukaemia is reported. A multiorgan involvement and fulminant course of the fungal infection resulted in the patient's death despite fluconazole prophylaxis, therapy with amphotericin B and administration of granulocyte colony-stimulating factor. Predisposing factors to the infection, clinical relevance of surveillance strains and in vitro antifungal susceptibility testing are discussed.

Amphotericin B↗
PubMed2001

The degree of bone marrow infiltration in patients with hairy cell leukemia treated with splenectomy compatible with long-term hematological remission.

To determine the degree of bone marrow infiltration with hairy cells which is compatible with long-term hematological remission in patients treated with splenectomy, we have investigated 7 patients surviving in hematological remission 61 to 255 months (median 184 months) after splenectomy. As hematological remission has been considered absence of hairy cells (HCs) in the peripheral blood, normalization of peripheral blood cell counts (hemoglobin 120 g/l, white cell count 4.0 x 10(9)/l, absolute granulocyte count 1.5 x 10(9)/l, platelet count 100 x 10(9)/l) and absence of lymfadenopathy and any other activity of the disease. For detection of HCs a very sensitive method of immunostaining with monoclonal antibody DBA.44 in our own modification has been used. Low values of sIL-2R which is considered to be a non invasive marker of tumor burden and activity in HCL were in agreement with the opinion that the bone marrow was the only locality of tumor involvement in splenectomized patients. Infiltration up to 20% with HCs (range 4% to 20%, median 10%) was found to be compatible with long-term hematological remission and long-term overall survival. Patient (No 1) with 30% infiltration of bone marrow with HCs, still normal peripheral blood cell counts, but a very high level of sIL-2R represents extraordinary finding which has been discussed in details.

Adult↗
PubMed2001

[Treatment of paroxysmal nocturnal hemoglobinuria (PNH)].

Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hematopoietic stem cell in which intravascular hemolysis is due to an intrinsic defect in the membrane of red cells that makes them increasingly susceptible to lysis by complement. The phenotypic hallmark of PNH cells is an absence or marked deficiency of GPI-anchored proteins such as CD 59+, CD 55+ and others which normally protect cells from the action of complement. PHN is closely associated with aplastic anemia. Some degree of bone marrow failure is always present. Management of PNH is complicated by a highly variable clinical picture and course. Some patients have severe anemia aggravated by hemolytic crises and associated thromboses. Bone marrow failure is accompanied with frequent infections and hemorrhagic manifestations due to thrombocytopenia. With the exception of marrow transplantation, no definite therapy is available. In the exceptional circumstance in which the patient has a syngeneic twin, bone marrow transplantation is the most appropriate therapy for severe PNH because of absence of graft-versus-host disease. In general syngeneic transplantation without preconditioning has been unsuccessful because abnormal hematopoiesis returns. Allogeneic bone marrow transplantation has been used, but the transplant-associated morbidity and mortality are high due mainly to the fatal graft-versus-host disease and severe posttransplant marrow failure. Use of an unrelated donor transplant has to be considered as contraindicated. PNH is associated with striking predisposition to intravascular thrombosis which often involves the portal system or the brain. Fatal thromboses account for about 40-50% of all deaths in patients with PNH. The etiology of the thrombophilia in PNH is not fully clarified. Anticoagulation or thrombolytic therapy is required for treatment of venous thrombosis, the latter vena cava. Prophylactic anticoagulation in patients without contraindications such as severe thrombocytopenia seems to be justified. However, whether such therapy may be efficacious in reducing the incidence of thromboses or affect survival is conjectural. PNH patients have varying degree of platelet activation and some authors suggest that antiplatelet therapy might be efficacious in reducing the incidence and severity of venous thrombosis in PNH. Pregnancy is hazardous. Female patients should avoid the use of oral contraceptives. Pregnant patients require combined care of an experienced hematologist and obstetrician specialized in the management of high-risk pregnancies.

Anemia, Aplastic↗
PubMed2000

[Determination of intracellular molecules in cells in hematopoietic malignancy using flow cytometry].

BACKGROUND: Detection of membrane molecules by immunophenotypisation is a routine counterpart of the laboratory tests which are needed for the complex diagnostic procedures of hematopoetic malignancies at present. The immunochemical detection of intracellular molecules is essential in such cases, where the expression of surface molecules on malignant cells is poor, or where the results of other diagnostic analyses are unequivocal (cases with ectopic expression of other lineage-specific molecules and cases of biphenotypic leukemias). METHODS AND RESULTS: We followed the procedure using 4% solution of paraformaldehyd in phosphate buffered saline for fixation of cells. Lysing solution G (Becton-Dickinson) was used for permeabilisation of cells to detect nuclear and cytoplasmatic molecules. The permeabilised cell suspension was than washed with 0.5% solution of Tween 20 in phosphate buffered saline. This simple and rapid procedure is readily available for the routine detection of intracellular molecules. This approach is important for the diagnosis of hematopoetic malignancies.

Antigens, CD↗
PubMed2000

[Monitoring minimal residual disease in patients with hairy cell leukemia in complete remission after treatment with 2-chlorodioxyadenosine].

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces in 85% patients complete remission. Complete remission is defined as the condition when signs of activity of the disease are absent, splenomegaly and lymphadenopathy are absent, the hemoglobin concentration is > or = 120 g/l, the absolute number of granulocytes is > or = 1.5 x 10(9)/l and the number of thrombocytes is > or = 100 x 10(9)/l. In complete remission in the peripheral blood, bone marrow aspirate and bioptic samples obtained by trephin bone marrow core biopsy, using standard staining (hematoxylin-eosin and May-Grünwald-Giemsa's method), no leukemic cells are present. When more sensitive methods are used (immunophenotyping, immunohistochemistry or molecular genetic methods), a persisting leukemic population can be detected which is described as minimal residual disease (MRD). For detection of MRD the authors used immunohistochemical examination of bone marrow with DBA.44 antibodies. As leukemic cells they described those which produced intense cytoplasmic and membrane positivity with antibody DBA.44 and corresponded morphologically to hairy cells. For evaluation computer analysis of the picture LUCIA-M was used. The infiltration grade was examined on three areas of standard size (3 x 65,265 micron 2) and expressed in percent. A total of 45 trepanobioptic specimens from 21 patients were examined who achieved after treatment with 2-CdA complete remission. In all samples suitable for evaluation the presence of leukemic cells (MRD) was detected with a median of 3% and a range of 1% to 18%. With induction of complete remission correlates also the low serum level of the soluble receptor for IL-2 (sIL-2R). In a female patient after 24 months of treatment with 2-CdA the grade of leukemic infiltration rose from 1% to 12% and during the 36th month to 50% DBA.44+ leukemic cells. The incipient relapse in this patient was not associated, despite marked infiltration of bone marrow, with failure of hematopoiesis and a marked rise of sIL-2R.

Adult↗
PubMed2000

[The treatment of multiple myeloma with an allogeneic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen].

Between November 1998 and October 1999 authors treated five multiple myeloma patients with an allogeneic peripheral blood stem cell transplantation from HLA-identical sibling using a non-myeloablative conditioning regimen. The median age at the time of transplantation was 58 (range: 47-65) years. In all patients one (n = 3) or two (n = 2) autologous peripheral blood stem cell transplantations were already performed. Conditioning was performed with fludarabine, oral busulfan and anti-T-lymphocyte globulin. All patients engrafted from 13 to 18 (median: 17) days from transplantation. The duration of neutropenia (absolute neutrophiles count < 500/microl) and thrombocytopenia (platelets < 20,000/microl) ranged between 4 and 19 (median: 18) and between 13 and 18 (median: 17) days, respectively. In the period of posttransplant pancytopenia two patients developed mild gastrointestinal mucositis and two pulmonary complications (bronchopneumonia and dyspnoe of unknown etiology). Two patients had grade III-IV acute graft-versus-host disease (GvHD), none had extensive chronic GvHD. Two patients received prophylactic donor-lymphocytes infusions 200 and 225 days from transplantation. One of them developed grade III acute GvHD. All patients responded. One achieved complete and four partial remission of the disease. One patient died 111 days from transplantation due to bronchopneumonia, four are alive and well, in the stable disease, 35, 36, 51 and 52 weeks after transplantation. It can be concluded that allogenic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen is an effective way of the multiple myeloma treatment with an acceptable toxicity.

Aged↗