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B Jaksić

Publications and source records attributed to B Jaksić.

At least 19 recordsLinked to original sources
PubMed2003

Prolegomenon for chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a unique lymphoproliferative disorder that scarcely occurs under the age of 40; thereafter the incidence of CLL increases exponentially with age. CLL is characterized by progressive expansion of malignant CD5+ME+ B-cell clone accompanied by a myriad of cellular and humoral immune defects. Each of them might be linked to different clinically manifested complications such as increasing rate of infections, autoimmune disorders and disturbed immune surveillance against tumour cells. We assume that CLL occurs as a consequence of age-dependent, genetically related functional restrictions of the thymic microenvironment in supporting common lymphoid progenitor cells (CD5+ME+CD4-CD8-) to differentiate into mature T-cell and B-cell descendants. In conjunction with genetic abnormalities developing in B-cell progenitors, presumably expressing P glycoprotein (Pgp+), we postulate that developmentally altered T-cell descendants, along with quantitative imbalance among CD4+, their subsets and CD8+ lymphocytes in the peripheral blood, play an important additional role in facilitating the malignant B-cell clone emergence and in modulating the CLL clinical evolution. Namely, imbalance of any of T-cell-mediated cell interactive homeostatic mechanisms accompanied by imbalance in the production of various cytokines might in CLL influence leukaemic B-cell growth by deregulating inducer (c-myc and p53) and/or suppressor (bcl-2 and mutant p53) oncogenes responsible for the promotion or suppression of B-cell mitogenesis that may in turn further contribute to their impaired differentiation and/or differentiation arrest. In conclusion, CLL might be interpreted as a primary immunodeficiency syndrome developing in elderly population due to gradually evolving restriction of genetically controlled programs in the thymic microenvironment responsible for irregular maturation of common lymphoid progenitor cells that constitutively express CD5 antigen and ME receptor into T-cell and B-cell descendants.

B-Lymphocytes↗
PubMed1998

Decision-tree approach to the immunophenotype-based prognosis of the B-cell chronic lymphocytic leukemia.

Use of a nonlinear prediction method, such as machine learning, is a valuable choice in predicting progression rate of disease when applied to the highly variable and correlated biological data such as those in patients with chronic lymphocytic leukemia (CLL). In this work, decision-tree approach to cell phenotype-based prognosis of CLL was adopted. The panel of 33 (32 different phenotypic features and serum concentration of sCD23) parameters was simultaneously presented to the C4.5 decision tree which extracted the most informative of them and subsequently performed classification of CLL patients against the modified Rai staging system. It has been shown that substantial correlation between the percentage of expression of the CD23 molecule on CD19+ B-cells, the level of sCD23, the percentage of CD45RA+, and the absolute number of CD4CD45RA+RO+ T-cells and the clinical stages, exists. The prediction vector, composed of their concatenated values, was able to correctly associate 83% of the cases in the low-risk group (Rai stage 0), 100% of the cases in the intermediate-risk group (Rai stage I and II), and 89% of the cases in the high-risk group (Rai stage III and IV) of CLL patients. Predictivity of this vector was 100%, 95%, and 89%, respectively. In conclusion, from the described analysis, it may be inferred that two processes play important roles in the progression rate of CLL: 1.deregulated function of the CD23 gene in B-cells accompanied by the appearance of its cleaved product sCD23 in the sera; and 2. functionally impaired and imbalanced CD4 T-cell subpopulations found in the peripheral blood of CLL patients.

Aged↗
PubMed1997

[Pseudothrombocytopenia caused by ethylenediaminetetraacetic acid (EDTA) (case report)].

Pseudothrombocytopenia is a laboratory artefact that can introduce serious problems in diagnosis and treatment in patients with low platelet count. The most common reason for this artefact is in vitro platelet clumping in blood samples collected into ethilenediaminetetraacetic acid (EDTA) anticoagulant. The clumping activity is greater at temperatures less than 37 degrees C, and the EDTA concentrations required for clumping are 20 times below anticoagulant concentrations. In this article we described the case of a female patient with diagnosed EDTA induced pseudothrombocytopenia. The cause of incorrectly low platelet counts was proved by simultaneous analysis in blood samples collected into EDTA anticoagulant and into heparin as a control sample. Absences of incorrectly low platelet count in heparin sample and rapid decrease of platelet count in EDTA sample were noticed. Decrease in platelet count was accompanied by increase in the number of leukocytes, so called pseudoleukocytosis. Careful examination of blood film is necessary to establish correct diagnosis, promptly after the blood collection and approximately two hours later. It is important to verify formation of clumps two hours after the blood collection and also progressive reduction in the platelet count in EDTA sample. By blood assessment conducted in this concern it is possible to avoid severe misinterpretation in such patients.

Adult↗
PubMed1997

Autoimmune thrombocytopenia in adults: clinical experience.

Diagnostic and treatment algorithms in autoimmune thrombocytopenia (AITP) are still somewhat controversial. We present our experience in the diagnosis and treatment of 39 AITP patients, hospitalized at our department between 1990 and 1995, and discuss alternative approaches. There were 10 male and 29 female patients, median age 47 (range 18-75) years. All patients had isolated thrombocytopenia and normal or increased number of megakaryocytes in bone marrow. Platelet count lower than 15 x 10(9)/L was found in 25 (64.1%) patients. Eighteen (54.5%) patients responded well to standard and two (6.1%) to high doses of steroids, whereas 18.2% of the patients responded well to other immunosuppressive therapy. Antiplatelet antibodies were found only in 4 (10.2%) patients. Our conclusion was that a half of adult AITP patients achieve satisfactory recovery on standard doses of steroids.

Adolescent↗
PubMed1994

The differential diagnostic capacity of serum amyloid A protein between infectious and non-infectious febrile episodes of neutropenic patients with acute leukemia.

We studied the behavior of four major acute phase proteins (SAA, CRP, ACT and AGP) in pyrexial occurrences of 16 neutropenic patients with acute leukemia. Altogether 37 febrile episodes were recorded; 27 were infectious in origin (microbiologically documented infection and clinically documented infection, MDI/CDI group) and 10 were pyrexias of unknown origin (PUO group). In the MDI/CDI group the mean value for the highest individual SAA concentration was 282 +/- 161 mg/l and in the PUO group 95 +/- 79 mg/l. The corresponding mean values were 4.0 mg/l (range 0.2-5.5 mg/l) in 10 control patients with 1 year remission and 0.8 mg/l (range < 0.1-1.2 mg/l) in 30 healthy adults. The peak value of SAA rose above 100 mg/l in 85% of our MDI/CDI pyrexias and in 40% of PUO. More reliable results were obtained when the difference between the value on the day when pyrexia occurred and the previous day was calculated. In that case, the difference was above 75 mg/l in 23 of 27 (85%) MDI/CDI pyrexias and in none of 10 (0%) PUO. In the MDI/CDI group the mean difference was 204 +/- 137 mg/l while it was only 26 +/- 19 mg/l in the PUO group. The statistical significance was very high (p < 0.0001). The CRP monitoring was very inferior to SAA while ACT and AGP monitorings were unsatisfactory.

Adolescent↗
PubMed1993

Functional differences of T cells in B-chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) is a disease characterized by an accumulation of monoclonal lymphocytes of B cell origin. Although the neoplastic process involves the B lymphocyte compartment, phenotypic and functional defects within the T lymphocyte population implicate their possible role in the pathogenesis of the disease. We analyzed the functional and morphological integrity of T lymphocytes from the peripheral blood of 64 patients with B-CLL. The activation of B-CLL T cells after PHA stimulation was determined by measuring [3H]-thymidine incorporation, assessing cell numbers in parallel cultures, and by monitoring the lymphocyte subsets during 9 days of cultivation. Our results indicate the presence of three functionally different populations of T cells in the peripheral blood of B-CLL patients. We present evidence for an increased proliferative potential of T lymphocytes from a group of patients with B-CLL.

Aged↗
PubMed1993

Myeloid hemopoietic growth factors. Review article.

The article is a critical review of recent publications on myeloid hemopoietic growth factors. They are glycoproteins that regulate the proliferation and differentiation of hemopoietic progenitor cells and the function of mature blood cells. They are also named colony stimulating factors after the experimental technique that led to their discovery. Myeloid growth factors are: granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF) and interleukin-3. Studies of hemopoietic growth factors in the past years have revealed many potential beneficial effects, but some limitations as well. They have been proved effective, above all, in neutropenic conditions of different origin. A large number of clinical trials have shown their beneficial effect in myelosuppressive conditions after cytotoxic chemotherapy, in post-transplant period in bone marrow transplantation procedures and in neutropenic conditions as part of other clinical entities. Although a number of studies that should determine their clinical role more clearly is still underway, it seems certain that myeloid hemopoietic growth factors already have an important role in modern pharmacotherapy.

Animals↗
PubMed1991

The roles of age and sex in the prognosis of chronic leukaemias. A study of 373 cases.

The roles of age and sex and their relationship to other prognostic factors were studied in 117 chronic myeloid leukaemia (CML) and in 256 chronic lymphocytic leukaemia (CLL) patients. Survival in CML was not related either to age at diagnosis or to sex. In contrast, the CLL patients classified into four age strata (less than 50, 50-59, 60-69, greater than 70 years) had an expected median survival (EMS) of 142, 101, 85 and 33 months respectively (chi 2 for heterogeneity = 35.59, P less than 0.0005; chi 2 for trend = 25.09, P less than 0.0005). Prognostic power was independent of sex, Rai stages, total tumour mass score (TTM), TTM distribution pattern, anaemia, thrombocytopenia, serum immunoglobulins and response to therapy. The relative survival rate (the ratio of patient's EMS and EMS in age- and sex-matched general population) was 0.40 in CLL patients and 0.13 in CML patients. Relative survival was more reduced in older CLL patients than in younger ones (0.37 vs 0.47, respectively), whereas relative survival was less reduced in older CML patients than in younger ones (0.18 vs 0.12, respectively). The results show that the age is a significant independent prognostic factor in CLL but not in CML. The difference in the effects of age on prognosis in CLL and CML most probably reflects the fundamental differences in their respective pathogeneses.

Age Factors↗
PubMed1991

[Relation between clinical parameters and histologic findings in patients with non-Hodgkin's lymphoma].

Clinical and morphological findings of lymph nodes in 150 consecutive untreated non-Hodgkin lymphoma (NHL) patients were retrospectively studied. One hundred and fifteen (77%) patients had B-NHL and 35 (23%) T-NHL, 96 (64%) patients had NHL low grade malignancy and 54 (36%) NHL of high grade malignancy according to the Kiel classification. Lymph nodes exceeding 2 cm in diameter (p less than 0.05), hepatomegaly (p less than 0.05), splenomegaly (p less than 0.05), and the duration of lymphadenopathy for more than 6 months preceding diagnosis (p less than 0.01) were significantly more common in low than high grade malignancy of NHL patients. Febrile episodes at the diagnosis were significantly more common in high than in low grade malignancy of NHL patients (p greater than 0.05). Lymph nodes exceeding 2 cm in diameter (p less than 0.05) in B-NHL, and lymph nodes above the diaphragm (p less than 0.05) and skin infiltration (p less than 0.001) were more common in T-NHL than in B-NHL patients. At the diagnosis low grade NHL patients have significantly more often splenomegaly, hepatomegaly, large palpable lymph nodes, and long lasting lymphadenopathy before diagnosis. High grade malignancy NHL patients have more often general symptoms, B-NHL patients have more often large palpable lymph nodes, T-NHL patients have more often skin infiltration and lymph nodes above the diaphragm. Precise clinical characterization of patients in addition to pathohistological diagnosis are very important in this highly variable disease.

Adolescent↗
PubMed1990

Prognostic value of cytophotometric analysis of DNA in lymph node aspirates from patients with non-Hodgkin's lymphoma.

To classify cases of non-Hodgkin's lymphoma in terms of expected clinical behaviour and survival, kinetic parameters measured by cytophotometry were assessed in 62 patients between 1978 and 1987. The influence of the number of cells with increased DNA content (more than 2N) on survival was evaluated. Analyses were carried out on the small samples obtained by needle aspiration biopsy of lymph nodes before treatment, using microdensitometry and Feulgen staining. Patients whose lymphomas contained less than 6% of cells with increased DNA content had a mean survival of 81.3 months and those whose lymphomas contained 6% or more of such cells had a mean survival of 18.5 months. A significant difference in survival using the same criteria was also noticed for patients with both low grade lymphomas and those with intermediate and high grade lymphomas. It is concluded that cytophotometric analysis of lymph node aspirates is of prognostic value in the initial assessment of non-Hodgkin's lymphoma.

Adolescent↗
PubMed1988

High dose continuous chlorambucil vs intermittent chlorambucil plus prednisone for treatment of B-CLL--IGCI CLL-01 trial.

279 B-CLL patients entered randomized IGCI clinical trial to compare the remission rate and survival of high dose continuous chlorambucil (regimen A) vs intermittent chlorambucil plus prednisone (regimen B), and to assess the effect of early treatment on survival. Regimen A was significantly better for remission induction (p less than 0.001), and prolonged survival (p less than 0.01) in comparison to regimen B. More aggressive chemotherapy is associated with better response but requires close monitoring of both antineoplastic effect and haematological toxicity. Total tumor mass score (TTM) proved to be suitable for definition of both early, stable disease and the response to therapy because of its quantitative continuous character and its independence of bone marrow failure. This system is helpful for the detection of treatment toxicity and consequently enables safe monitoring of therapy. Although statistically significant difference has not yet been reached between the patients treated early and non treated patients the latter group seems to fare better.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Modulation of chronic lymphocytic leukemia (CLL) lymphocyte phenotypes by in vitro incubation with alpha 1 thymosin.

In this study an attempt was made to elucidate (1) the level(s) of differentiation arrest of B cells, and (2) whether T-cell functional defects in CLL patients are related to their defective maturation. In addition, an attempt was also made to induce and/or correct maturation of T cells in CLL patients by in vitro incubation with alpha 1 thymosin. In CLL patients and controls, we determined the percentage of T and B cells with T11, T8, T4, C3, and mouse erythrocyte (ME) receptors, along with T-cell functional reactivity (measured by local xenogeneic graft vs host reaction), before and after incubation with alpha 1 thymosin. In about 60% of stable CLL patients, and in 80% of those in the progressive phase of disease, T cells possess receptors for ME and/or C3. After incubation with alpha 1 thymosin, separate analysis of surface markers on T and B cells revealed (along with the induction of T11 receptors on T-cell surface) induction of ME receptors on T and B cells in stable phase and selective loss of ME receptors on B cells in the progressive phase of CLL. After incubation of normal lymphocytes with alpha 1 thymosin, we observed an increase of T8 receptors, no change in expression of T11, and a decrease of T4 receptors along with the increase of the intensity of T-cell functional reactivity. In contrast, in CLL patients following incubation with alpha 1 thymosin, the induction of T8 receptors was less prominent in the progressive than in the stable phase of disease. Furthermore, induction of T8 receptors in CLL patients in the stable phase was accompanied by recovery of impaired or increase of preserved functional T-cell reactivity. In the progressive phase, however, T-cell functional areactivity remained unchanged. The findings suggest that different levels of B-cell-differentiation arrest along with defective maturation of T cells might be responsible for the spectrum of disease evolution in CLL.

Cell Differentiation↗
PubMed1987

Clinical relevance of peripheral blood lymphocyte morphology and lymph node histology in chronic lymphocytic leukemia.

Peripheral blood lymphocyte (PBL) morphology and lymph node (LN) histology were evaluated in a prognostic study conducted in 247 patients with low-grade malignancies of B lymphocytes. The patients were classified according to total tumor mass (TTM) distribution pattern. A simple classification based on quantification of lymphoid cells that were morphologically different from small lymphocytes of peripheral blood was evaluated in the 166 leukemic patients. The lymph node histology was studied in 211 patients who had lymph node enlargement. The pattern of growth (pseudofollicular, diffuse, and tumorous), the proportion of distinct lymphocytes, and the degree of capsule infiltration were evaluated in 130 patients who showed leukemic involvement as well as enlargement of lymph nodes and/or spleen. Both PBL and LN morphologies correlate with the TTM distribution pattern and demonstrate a prognostic value that is independent of clinical characteristics. From the PBL morphology the LN morphology can be predicted. The prognostic power of the PBL morphology is lost after adjustment for the pattern of growth in LN and vice versa. A significant overlap between the PBL morphology and LN histology suggests some independence between the two variables and points to the possibility of biased classification if only one of the compartments is evaluated. Capsular infiltration is, however, a prognostic factor independent of both clinical and morphological characteristics. Morphological analysis in CLL is clinically relevant. Precise classification of patients requires analysis of both PBL and LN morphology to ensure comparability of patients admitted to clinical trials.

Adult↗
PubMed1985

The relationship between membrane characteristics, functional reactivity of T-lymphocytes, and the progression rate of B-cell chronic lymphocytic leukemia.

Study performed on 192 patients has demonstrated that the progression rate of chronic lymphocytic leukemia (CLL) is associated with the existence of T-cell defect(s). A dynamic classification system based on evaluation of tumor mass growth rate, response to therapy, and myelopoietic failure (MF) has been devised for evaluation of progression rate of CLL. Besides four basic groups (Group 1: CLL without therapy; Group 2: CLL on therapy, without remission; Group 3: CLL on therapy, partial remission; Group 4: CLL on therapy, complete remission) patients were further classified into phase (type) A (stable, indolent CLL) or phase (type) B (active, progressive CLL). The major criteria for phase A were: total tumor mass (TTM) doubling time (DT) longer than 12 months, no MF, and/or good response to therapy. The major criteria for phase B were: TTM DT less than 12 months and/or accompanying MF and/or no response to therapy. The following major findings have been demonstrated: (1) altered quantitative relationship between active and nonactive parts of T-cell compartment (E/A ratio) in the progressive phase of CLL; (2) altered B/T gamma ratio in the progressive phase of CLL; (3) more than 50% increased percentage of T gamma cells in the stable phase of CLL; (4) very low stable and absent seeding efficiency of T-cells in the progressive phase of CLL; (5) altered (delayed) DNA synthesis pattern in the progressive phase of CLL; and (6) negative local xenogeneic graft versus host reaction in the progressive phase of CLL. Based on reported results, a hypothesis regarding the possible role of T-cells in the pathogenesis of CLL was suggested.

Animals↗