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B Mihaljević

Publications and source records attributed to B Mihaljević.

14 recordsLinked to original sources

Ki-67 proliferative marker in lymph node aspirates of patients with non-Hodgkin's lymphoma.

Proliferative activity of lymphoma cells was tested by immunocytochemical staining with Ki-67 monoclonal antibody in 63 aspirates of peripheral lymph nodes sampled from patients suffering from non-Hodgkin's lymphoma. Referring to the dominant cell population in nodal aspirates, a rising trend of Ki-67 proliferative marker was noted from the small cells (X = 13.20) and small cells with notched nucleus (X = 43.52) and large cells (X = 79.47) with histopathologic equivalents corresponding to aggressive lymphoma. Statistical testing of the difference in the Ki-67 proliferative marker against demographic and clinical-laboratory characteristics of the studied patients revealed the levels of significance for the performance status, bone marrow infiltration, and albumin serum value. Correlation of cytomorphological and immunocytochemical results was tested against International Prognostic Index (IPI). Statistically significant correlation of Ki-67 with cytomorphology and REAL-immunocytochemical classification of lymphoma was confirmed, but not with the IPI index. In order to determine the prognostic importance of Ki-67 marker, the patients were classified into those with low Ki-67 (<20% of proliferating cells), mean proliferation index Ki-67 (range 20-59%), and high proliferative index Ki-67 (positive in over 60% of lymphoma cells). Testing Ki-67 with survival we have found that the low proliferative index was associated with the longest survival, median about 36 mo; for proliferative marker values ranging between 20 and 59%, the median survival was 30.4 mo; and survival of patients with the high proliferative index was only 12.9 mo.

Adult↗

Primary extranodal lymphomas of gastrointestinal localizations: a single institution 5-yr experience.

This study is aimed at comparison of patients with extranodal lymphomas based on pathohistological findings differences (MALT vs non-MALT) as well as regarding gastric and non-gastric localization, and determining the significance of clinical-laboratory parameters with respect to therapeutic response and length of survival. A total of 56 patients with extranodal non-Hodgkin's lymphomas of the gastrointestinal tract were evaluated over a 5-yr period. Regarding the localization of the disease, the stomach was most frequently affected, 39 patients (70%); followed by small and large intestines, 17 patients. As for the pathohistological findings, MALT lymphoma accounted for 70%, DLBCL 25%, while other subtypes accounted for 5%. Patients' distribution was analyzed according to CS based on both Ann Arbor and Lugano systems; however, the difference obtained between the groups was not statistically significant in both staging types of patients. Statistically significant difference in patients' distribution was not found with respect to IPI index, bone marrow infiltration, anemia, hypoalbuminemia, or histological subtype and localization. Difference in survival between patients according to the pathohistological type was not statistically significant also according to the type of the affected gastrointestinal tract organ. Statistical significance of difference according to survival probability was obtained based on age (survival is longer in patients over 55 yr of age); according to CS and according to Ann Arbor and Lugano classifications (the patients with lower CS live significantly longer); according to IPI index (the survival is significantly longer in patients with lower probability: IPI-0,1, and 2), as well as patients free of bone marrow infiltration whose survival is also significantly longer.

Adolescent↗

The reevaluation of the ferric thiocyanate assay for lipid hydroperoxides with special considerations of the mechanistic aspects of the response.

The mechanistic aspects of the spectrophotometric method of analysis of lipid hydroperoxides (LOOH) based on the oxidation of ferrous to ferric ion and subsequent complexation of the latter by thiocyanate are considered. The method of analysis, as revised by us, was carried out in the same solvent that had been used for the extraction of lipids from the sample, a deoxygenated chloroform:methanol or a dichloromethane:methanol (2:1, v/v) mixture, and used a single solution containing both reagents, Fe2+ and SCN-, for developing the response. In that solvent, total lipids up to 5 mg/ml did not interfere, and linear increase of the absorbance of ferric thiocyanate complex was obtained up to 2 x 10(-5) M LOOH. Molar absorptivity of the ferric thiocyanate complex expressed per mol of LOOH was determined as 58,440 M-1 cm-1, based on the average of four ferric ions produced by each LOOH molecule. The estimated lowest detectable limit was about 170 pmol LOOH/ml of analyzed solution, which corresponded to about 50 mumol LOOH/kg lipid in complex natural mixtures. In addition to good sensitivity, and in contrast to some other more popular spectrophotometric assays for LOOH, the method is responsive also to hydroperoxides of mono- and di-unsaturated fatty acids. The method, thus, provides an easy, rapid, sensitive, and complete measure of hydroperoxidation of lipids.

Cobalt Radioisotopes↗

Acute megakaryoblastic leukaemia with mediastinal tumor.

Acute megakaryoblastic leukemia (AMKL) is a rare myeloproliferative syndrome with a fulminant clinical course characterized by progressive pancytopenia, pallor, weakness and severe hemorrhage. We present a 18-year old male with pancytopenia and massive hemorrhage, lymphadenopathy, organomegaly, and with unusual presentation of retrocardial mediastinal tumor on the right side. The diagnosis of AMKL was established by combining cytological and immunocytochemical analyses of peripheral blood cells (blasts were GPIIIa and GPIb positive); by immunohistochemical analysis of lymph node (dysplastic megakaryocytes were GPIIIa and F VIII positive); in vitro culture studies confirmed enormous growth of CFU-Mk with high proliferative capacity. In spite of therapy, the patient died 3 months after the first signs of the disease.

Adolescent↗

Angioimmunoblastic lymphadenopathy (AILD) with benign course.

A group of rare systematic lymphoproliferative disorders have been described under the heading of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), from purely reactive to bona fide malignancies. Some patients exhibit a benign form of disease, but most exhibit an aggressive form with high mortality rate. We present two elderly patients with prominent constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, diffuse maculopapular rash, polyclonal hypergammaglobulinaemia and immunohaemolytic anaemia. Lymph node biopsies showed features consistent with the diagnosis of AILD. The patients were treated with steroid and they are in complete remission 3.5 and 2.5 years, respectively after the diagnosis has been established.

Aged↗

mb-1: a new marker for B-lineage lymphoblastic leukemia.

The expression of the Ig-linked mb-1 polypeptide was analyzed by immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase technique) using a specific monoclonal antibody in 165 cases of acute leukemia, with 88 being lymphoblastic (ALL) and 77 myeloid (AML). The purpose of the study was to investigate the specificity of this reagent for B-lineage cases and its reactivity on leukemias that coexpress myeloid and B-cell antigens (biphenotypic). The majority (89%) of 72 B-cell precursor ALL patients were positive. Of these, mb-1 was expressed in all 9 patients with early-B-ALL (CD10-, c mu-), in all 11 patients with pre-B-ALL (c mu+) and in the single case of B-ALL (smIgM+). Forty-three of 51 patients with common-ALL (CD10+, c mu+) were also positive. All 16 T-lineage ALL patients and 72 (93.5%) of the AML patients examined were mb-1 negative. Four of the 5 mb-1-positive AML patients were considered biphenotypic and expressed other B-cell antigens such as CD10, CD19, and/or cCD22 and all showed rearrangement of the Ig heavy chain genes. Within the AML cases, mb-1 and cCD22 were more useful than other B-cell antigens in detecting biphenotypic cases, and mb-1 showed the highest correlation with the clonal rearrangement of Ig heavy chain genes. These results indicate that mb-1 is a sensitive and specific reagent for B-lineage blasts that will aid in the classification of B-cell precursor ALL and in the identification of biphenotypic leukemia presenting as AML.

Antibodies, Monoclonal↗

[Angioblastic lymphadenopathy--its course and prognosis].

INTRODUCTION: In recent years important advances have been made in the understanding of angioimmunoblastic lymphadenopathy since substantial controversy has been related to the name, course, prognosis and therapy of the disease. It was first recognized in the Kil Classification as a low risk T-cell lymphoma [5], and omitted from the most widely used Working Formulation for clinical purposes. According to the criteria of REAL (Revised European American Lymphoma), classification angioimmunoblastic lymphadenopathy (AILD) is one of peripheral postthymic T cell lymphomas that are an immunologically defined category of non-Hodgkin's lymphomas originating from the peripheral lymphatic tissues. Morphologically, AILD is characterized by partially or completely obliterated sinuses and frequent infiltration of the pericapsular tissue and substantial proliferation of epithelioid, postcapillary venules. Cytologically, polymorphous cellular infiltration with immunoblasts, transformed lymphoid cells, polyclonal plasma cells, eosinophils and epithelioid cells are found. Clinically, rapid occurrence of systemic symptoms in elderly individuals (sixth and seventh decades of life) with generalized lymphadenopathy, hepatosplenomegaly and cutaneous maculo-papulous or erythematous rash is noted. The patients are characterized with hyperimmune condition in the form of Coombs' positive haemolytic anaemia, polyclonal hypergamma-globulinaemia and liability to infections [8, 9]. In spite of numerous suggestions, therapeutic consensus has not been achieved, and the reported survival ranges from 1 to 30 months [10, 11]. Therefore, this information suggests an aggressive form of the disease with the 60% mortality rate. METHODS: At the Institute of Haematology of the Clinical Centre of Serbia in Belgrade in the last five years, from 1993 through August 1998, nine patients were diagnosed with AILD according to the results of pathohistological examination of the extirpated peripheral lymph nodes and the correlation with clinical picture and relevant laboratory findings. RESULTS: Clinical characteristics of nine patients in whom AILD was diagnosed after lymph node biopsy are given in Table 1. The group consisted of 6 men and 3 women, mean age 53. Eight patients were in advanced stage of the disease at the time of the diagnosis (III and IC CS), while the patient in II CS stage had a large tumorous mass (M+). All patients had initial systemic symptoms. Five of them developed fever with chills. Three patients had evidence of extranodal infiltration of the bone marrow. Infiltration of the liver was suspected in two patients according to aberrant hepatogram values, although pathohistological verification was not obtained. In one patient lung infiltration was histologically verified in addition to bone marrow and liver infiltration. All patients had peripheral lymphadenopathy, and most of them hepatosplenomegaly, as well. Three patients had the so called bulky form of the disease since the diameter of the largest tumour exceeded 10 cm. On admission, most were in poor overall condition, and only two were apparently healthy. Knowing that AILD is basically an immunoregulatory disease and that the described cases of association with systemic diseases of the connective tissue and some drugs were implied in the triggering of AILD, Table 2 shows important information obtained form histories of these patients. Namely, 7 of 9 patients had cutaneous changes suggestive of erythematous or maculopapular rash, while three had received corticosteroid therapy for months before AILD was diagnosed since toxoallergic exanthema had been incorrectly suspected. Three patients received gold sodium thiosulfate therapy for rheumatoid arthritis, while four had history of allergy to drugs and pollen. Table 3 shows laboratory results: anaemia was present in 8 of 9 patients, it was severe in three with haemoglobin values of 67 g/L, 72 g/L and 50 g/L, respectively. Five patients had haemolysis. A

Adult↗

[Primary gastrointestinal non-Hodgkin's lymphomas].

A retrospective study of seventeen patients with primary gastrointestinal Non-Hodgkin's Lymphomas (GI-NHL) is presented. The sites of location were: the stomach (12 patients), the small intestine (2 patients), the ileocecal region (1 patient), the colon (1 patient), the stomach and the small intestine (1 patient). The mean age of the patients was 45.5 years. Histopathologic features were classified in accordance with the Working Formulation. Radical surgical resection of the tumour was performed in 14 patients. Laparotomy and biopsy were performed in one patient. The cases were grouped on the basis of: physical examination, surgical report and additional studies (bone marrow biopsy, lymphangiogram, radiograms..). Dawson et al have cited four criteria necessary for lymphoma of GI tract to be primary considered: 1) no enlargement of peripheral or mediastinal lymph nodes; 2) normal white blood cell count; 3) predominance of alimentary tract lesions with only regional lymph node involvement; and 4) no involvement of liver and spleen. After the surgical resection a combined chemotherapy was used in 15 patients. The operation was followed by irradiation in one case. Chemotherapy was refused by one patient. The better outlook in primary gastric lymphomas than in intestinal lymphomas was noted. The majority of investigators reported that gastric lymphoma was associated with better prognosis than intestinal lymphoma, one possible explanation being that gastric lymphoma was more likely to be diagnosed at an earlier stage.

Gastrointestinal Neoplasms↗

[Non-Hodgkin's lymphoma of the thyroid gland--2 case reports].

The authors present two female patients with Non-Hodgkin's lymphoma of the thyroid gland. The first had Non-Hodgkin's lymphoma, follicular, diffuse of centrocytic cells (FCC-intermediate grade risk), and the second had an immunoblastic Non-Hodgkin's lymphoma with large cells (high grade risk). After "staging" procedures, it was estimated that the first patient was in I EA and the second in II EB clinical stage. They were treated by surgical removal of involved tissue, combined chemotherapy and local radiotherapy. A complete remission was achieved in both patients without signs of recidivation for 8 months in one patient and 18 months in the second subject, after treatment. The elder patients more often manifest this type of lymphoma, especially if they already had chronic thyroiditis of Hashimoto's type. Using the combined, contemporary treatment, the overall five-years survival is about 56 +/- 7 percent.

Aged↗

[Treatment of aggressive non-Hodgkin's lymphoma with the ProMACE- CytaBOM protocol].

INTRODUCTION: The Working Formulation Classification (for clinical use) divides non-Hodgkin's lymphoma (NHL), according to the nature of the disease and response to therapy into the low, medium and high risk lymphomas. Although these subgroups include different pathohistological types of NHL, they are considered sufficiently homogenous for joint therapy planning [1]. The first generation protocol (CHOP) managed to achieve complete remission (CR) in 50-55% of patients with 30-35% of survival rate [2]. A large four-branch comparative study of SWOG group compared CHOP as the first generation protocol with the third generation protocols ProMACE CytaBOM, m-BACOD and MCOD-D. The results have shown a similar CR and survival rates, so that CHOP is considered a gold standard for the treatment of aggressive NHL [6]. In the light of individual reports stating a high CR rate in the treatment of aggressive NHL by ProMACE CytaBOM [3-5] we present our experience and observations related to the use of this protocol. METHOD: Over the period from 1991 through May 1996 at the Department of Lymphoproliferative Diseases, Institute of Haematology, Clinical Centre of Serbia in Belgrade, we treated 25 patients with pathohistologic evidence of medium to high risk lymphomas, where cases of lymphoblast lymphoma and Burkit's lymphoma were excluded. The median follow-up was 27 months (maximum 63 months). RESULTS: Four of 25 patients were > 60 years. Three of these died. Pathohistological analysis revealed that of 20 cases of medium risk aggressive lymphoma five had diffuse, small cleaved cells, 7 had diffuse mixed and 8 diffuse centroblast cells. Although diffuse NHL with small cleaved cells is classified into clinically indolent lymphomas, two of five patients were in the fourth clinical stage, and three of five patients had a large tumorous mass. In the high risk group five patients had immunoblast lymphoma. Karnofsky index was high in 20/25. According to Ann Arbor criteria 19/25 patients were in IVCS and 7/25 had a large tumour mass. Most patients had clinical symptoms (21/25). Extranodal localization was confirmed in 19 patients. Bone marrow and hepatic infiltrations were most common: 9 and 6 patients, respectively. Eleven patients had a single extranodal localization, while 8 had 2 or more. The median follow-up was 27 months (maximum 63 months), and 21/25 (84%) patients responded to therapy (CR + PR). Complete remission was achieved in 14 patients (56%), and PR in 7 (28%) patients. In the CR group two died, and relapse developed in one after 28 months. In 11 cases CR is maintained. The average duration of CR was 16 months (3-38 months), and PR was maintained for 6 months (20 months in one case). The average survival was 24.5 months (range 3-53). DISCUSSION: The fact that a half of adult patients with disseminated aggressive NHL can be cured with combined chemotherapy is the major oncological achievement in the last 20 years. The protocol combines 4-8 drugs, and the joint report of the SFOG group for lymphoma in over 1200 patients with lymphoma has shown that the second and third generation protocols are not more effective than the standard CHOP or CHOPBleom protocols [6]. The optimum therapeutic protocol in the treatment of aggressive lymphoma is still unpredictable due to the fact that it is inadequate to compare the results of individual institutions with the results of collaborative groups; there is also a significant difference in the prognostic factors in different research groups; there is no sufficient complete and published results that suggest the lower CR than the original reports (which may be related to the evaluation of tumour and remission). There are not sufficient data on the incidence of secondary carcinoma and leukaemia [1]. The decision on the therapy should be based on two lines of information: those related to each particular patient (age, associated diseases) and those related to the tumour (large mass, immunophenotyping, cytoge

Adult↗