-
[show abstract]
[hide abstract]
ABSTRACT: Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this
study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological
features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients
with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard imunohistochemical method
of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and
p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical
stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet
count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration,
histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant
difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo,
p=0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations
of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.
Medical Oncology 04/2012; 21(1):73-79. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIM: Primary resistant acute myeloid leukemia has a very poor prognosis. We assessed pretreatment parameters for their significance as prognostic factors in the overall survival (OS) of 53 acute myeloid leukemia (AML) patients who had failed to achieve complete remission (CR) after first-line standard-dose remission-induction therapy. RESULTS: During the period January 2005-December 2009, 53 with acute myeloid leukemia received two cycles of the 3+7 protocol as a first-line standard-dose remission-induction therapy (ARA-C, days 1-7 and daunorubicin, days 1-3). The HiDAC (5 patients), MiDAC (7 patients), and FLAG-IDA protocols (3 patients) were given as salvage therapy. None of these patients achieved CR. There were 27 (51%) males and 26 (49%) females (median age, 55 years, range 28-76). The median white blood cell count was 53 (range 0.9 -350)×10(9)/L, platelets 44 (range 3-856×10(9)/l) and bone marrow blasts 67%. HCT-IC comorbidity scores were 3 in two (3.8%) patients, 2 in 11 (20.8%), 1 in 12 (22.6%) and 0 in 16 (30.2%) patients. Median OS was 3.9 months (range 1 -20 months). The hepatomegaly, white blood cell count, ECOG PS, serum level of lactate dehydrogenase, dysplastic changes, coexpression of CD64, CD15, CD11b, comorbidities and disease cytogenetics influenced survival. CONCLUSION: This single-center study evaluated the significance of pretreatment factors, and found that patient age, comorbidities, ECOG performance status, leukocytosis, hepatomegaly, LDH, and the disease cytogenetics were factors which influenced the outcomes of primary resistant patients with acute myeloid leukemia. An understanding of these factors may help to predict OS in cases where CR has not been achieved and may help when making further treatment decisions.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12/2011; · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Treatment options are limited in patients with chronic immune thrombocytopenic purpura (ITP) which has been unresponsive to corticosteroids and/or splenectomy. Mycophenolate mophetil (MMF) is effective in many autoimmune disorders including severe and refractory ITP through its targeting of T-cell and B-cell lymphocytes. We report on the efficacy of MMF (1.5-2 g/day) in 16 adults with severe steroid-resistant ITP. MMF was administered for at least 12 weeks (median 37 weeks, range 14-64 weeks). Patients comprised of 10 females and six males, with median pre-treatment platelet counts of 8 × 10(9)/L, median age of 55 years, median ITP duration of 58 months and a median of four prior treatments (range 3-8); nine had been previously splenectomized. Eleven patients (69%) responded after 12 weeks of MMF: 6 (55%) achieving complete remission (CR) and five (45%) achieved partial remission (PR). MMF therapeutic responses were better in those patients who had had fewer prior treatments (p<0.05), and were independent of patient age, sex, disease duration, and splenectomy status (p>0.05). Five of the 11 responders (45%; 3CR/2PR) had sustained remissions; however, six responders (55%; 3CR/3PR) relapsed after median of 14 weeks (range 9-20). Three of the six relapsing patients responded to MMF reinstitution achieving stabile PRs; three were left untreated as none had further bleeding and their platelets remained at "safe" levels (median 30 × 10(9)/L). The MMF treatment was well tolerated; one heavily pretreated patient developed a bronchopneumonia and a second had an episode of diarrhea. MMF used as a second-line agent can produce a sustained response in severe ITP which has been unresponsive to steroid and/or splenectomy without major toxicity.
Platelets 01/2011; 22(2):153-6. · 1.85 Impact Factor
-
M Todorovic,
B Balint, N Suvajdzic,
M Jevtic,
M Pavlovic,
M Petrovic,
M Krstic,
V Popovic,
B Ivanovic,
I Elezovic,
R Milenkovic,
M Colovic
[show abstract]
[hide abstract]
ABSTRACT: Paragangliomas are tumors arising from the extra-adrenal paragangliar neural crest cells. The sympathoadrenal neuroendocrine system consists of extra-adrenal paragangliar cellular layer along the paravertebral and para-aortic axis, and the adrenal medullae. Paraganglioma should be included in the differential diagnosis of secondary erythrocytosis due to its possible ectopic erythropoietin (EPO) secretion. Thus, in this report we present a 24-year-old female patient with onset of unregulated ectopic EPO secretion, and consecutive erythrocytosis followed by hypertension, secondary to paraganglioma of multifocal retroperitoneal localization. Clinical, laboratory, and radiological investigations confirmed both an elevated EPO level and the presence of multiple paraganglioma. This paraneoplastic-mediated medical condition with high risk of cellular hyperviscosity syndrome (CHVS) requires prompt diagnosis and rapid therapeutic interventions. Initially, simple phlebotomy procedures were used; following that, tumors were surgically removed. In the course of the disease, this tumor relapsed, and urgent apheresis, as a treatment of life-threatening state, was used. The therapy performed resulted in a rapid blood viscosity depletion and a significant (P < 0.01) serum EPO reduction, as well as the general clinical benefit. Therefore, we conclude that the use of our own "multi-manner" apheresis (erythrocythapheresis plus plasma exchange), for long-time interval (until further causative therapy), effectively cross-bridged the possible hazards of EPO-dependent CHVS.
Medical Oncology 01/2008; 25(2):148-53. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The coexistence of systemic lupus Erythematosus (SLE) and multiple myeloma (MM) is uncommon and the pathogenetic mechanisms underlying this association remain unclear. We report the case of a woman who was diagnosed with SLE in 1993 aged 57, then developing IgA lambda type MM in the IIB clinical stage 7 years later. The SLE was treated successfully with methylprednisolone and chloroquine, and low dose maintenance steroid was continued with bisphosphonate protection until December 1994 when she suffered multiple vertebral fractures. She continued to receive 4 mg alternate day methylprednisolone and calcitonin until she decided to discontinue her own treatment 2 years later. In 2000, while still in stable SLE remission, she was diagnosed with MM. Protein electrophoresis revealed the IgA lambda paraprotein (40.5 g/l) and she had a Bence Jones (BJ) proteinuria of the lambda light chain type. Bone marrow trephine biopsy revealed a massive patchy infiltrate of abnormal plasmocytes (70%), while an extensive x-ray skeletal survey did not show any new fractures or osteolysis. The patient was treated according to the VMCP protocol without attaining a plateau phase. There was a similar poor clinical response to second and third line treatments (VAD, Thalidomide, Melphalan, and high dose dexamethasone). After 4 years of refractory disease the patient died from severe bilateral pneumonia. This case is discussed with reference to the literature.
Medical Oncology 02/2007; 24(4):445-8. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The clinical, cytogenetic, and immunophenotypic features in 12 adult patients with acute panmyelosis with myelofibrosis (APMF; ICD-0-3: 9931/3; C42.1) are reported (median age: 57 years; f/m = 1.4). The white cell count (WBC) was normal in 3 patients; 9 had leucopenia. The median hemoglobin value was 64.5 g/l, and median platelet count 12 x 10(9)/l. Bone marrow biopsy showed a hypercellular marrow in 10/12 patients with a significant infiltration of pathological blasts (range: 30 - 60%). All the cases had marked reticulin fibrosis. Immunophenotyping of bone marrow blast cells showed the expression of early (CD34) and lineage-unspecified antigens (HLA-DR) in 6/7, and 7/7 patients, respectively. "Early" myeloid antigens (CD13, CD33) were seen in 6/7 and 4/6 patients respectively. Monocyte antigen (CD14) was expressed in 3/7 patients. Megakaryocyte antigen (CD61) and erythroid cell antigen (GpA) were each expressed in only 1 patient. Two patients had expression of CD34, HLA-DR and "early" myeloid antigens by their bone marrow blast cells and 1 of these also had a co-expression of the antigens from a differentiated monocytic cell proliferation (lysozyme+, CD68+). Nonspecific chromosomal aberrations were recorded in 8/10 patients. The median survival was 2 months. These findings suggest an immature myeloid phenotype of blast cells in APMF. In 6/9 patients a leukemic cell differentiation into monocytic, megakaryocytic or erythroid lineage was also demonstrated.
Leukemia and Lymphoma 10/2004; 45(9):1873-9. · 2.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.
Medical Oncology 02/2004; 21(1):73-80. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effect of Tiazofurin (TR) on the in vitro growth of bone marrow (BM) and peripheral blood (PB) leukemic progenitors was investigated in 29 patients. Nineteen of the patients were suffering the blast crisis of chronic myeloid leukemia (bcCML) and ten patients refractory acute myeloid leukemia (AML). PB and BM mononuclear cells were cultured in methylcellulose alone or with concentrations of TR ranging between 10 and 200 microM. TR produced a dose dependent inhibition of colony forming unit (CFU)-blast growth in all the samples tested from BM and PB. The most effective concentrations of TR used were 150 and 200 microM, while concentrations of less than 50 microM TR were not adequate for 50% inhibition of cell growth (IC50). Differences were found in the response of CFU-blasts to TR related to the type of underlying leukemia. Inhibition of CFU-blast growth was more pronounced in bcCML than in AML in both the BM and PB samples. The concentration of TR required to induce IC50 in bcCML was 50 microM, while the same effect in AML required a concentration of 150 microM. Analysis of the control samples also revealed that CFU-blasts from bcCML produced smaller numbers of colonies, though these differences were not statistically significant. It has therefore been demonstrated that TR has strong in vitro anti-leukemic activity, more pronounced in bcCML than in refractory AML. We thus feel this study gives further rationale for the clinical application of TR, and would strongly support this.
Cancer Letters 07/2003; 195(2):153-9. · 4.24 Impact Factor
-
IARC scientific publications 02/2002; 156:231-2.
-
[show abstract]
[hide abstract]
ABSTRACT: Primary plasmacytoma of the lung is a rare tumor, thus presenting a diagnostic challenge to the clinician. So far, approximately 20 cases have been verified by immunohistochemistry. We describe an elderly patient presenting with progressive dyspnea on exertion, dry cough, weight loss and malaise. The main finding on plain chest radiography was a diffuse infiltration of pulmonary parenchyma in the lower parts of both lungs and in the middle part of the right lung. The histology of the open lung biopsy of the right middle lobe revealed massive and diffuse infiltration by well differentiated plasma cells with extracellular deposits of amyloid. The plasma cells and amyloid expressed a monoclonal lambda light chain. No monoclonal spike was shown by serum and urine immunoelectrophoresis. A skeletal survey and bone marrow biopsy specimen excluded a disseminated disease and a diagnosis of extramedullary plasmacytoma was made. The patient was considered for VI courses of VMCP chemotherapy after which a complete regression on chest roentgenography was evident. Almost five years after the diagnosis the patient is still alive without any evidence of disease recurrence or dissemination.
Haematologia 02/2001; 31(2):161-5.
-
[show abstract]
[hide abstract]
ABSTRACT: The authors report a 58-year-old female who originally presented with acquired pure red cell aplasia (PRCA). At diagnosis, the karyotype was normal, the serum erythropoietin level was highly elevated and no T-cell mediated inhibition of erythropoiesis was demonstrated in coculture studies. Conventional immunosuppressive therapy proved ineffective. A year later a diagnosis of hyperfibrotic myelodysplastic syndrome was assessed. The sequential bone marrow examinations in the course of the three years showed a progressive increase in bone marrow fibrosis, erythroid hyperplasia and dysmegakaryocytopoiesis, terminating in the acute myeloid leukemia. This sequence of the events included the appearance of del(5)(q13q33), four years after setting a diagnosis of PRCA. The authors suggest that the absence of both cytogenetic abnormality and the signs of dyshematopoiesis at the diagnosis of PRCA does not exclude ultimately a "clonal" category of the disease. Thus, repeated hematological and cytogenetical reevaluations are recommended.
Hematology and Cell Therapy 03/1999; 41(1):27-9.
-
[show abstract]
[hide abstract]
ABSTRACT: A patient with chronic idiopathic thrombocytopenia and fatal strongyloides hyperinfection syndrome following prolonged corticosteroid therapy is briefly described. Diagnosis was difficult to perform due to absence of eosinophilia and diarrhea at presentation, as well as to the negativity of multiple stool specimens examined by direct microscopy of saline smear, formol-ether concentration techniques, and Baermann's test. The striking hypoalbuminemia in the setting of the normal results of liver function tests and prothrombin time was assumed to be due to enteropathy. Therefore, an upper endoscopy was undertaken, revealing Strongyloides stercoralis (SS) larvae in the biopsy specimens of the gastric and duodenal mucosa. The SS larvae were also demonstrated in the multiple specimens of the concentrated sputum. Despite thiabendazol treatment, death ensued. On autopsy, SS larvae were recovered in the gastrointestinal tract and lungs. The importance of early diagnosis and of ruling out strongyloidosis prior to administration of corticosteroids are discussed, as well as the pathogenetic aspects of strongyloidosis in the patient under corticosteroids.
Haematologia 02/1999; 29(4):323-6.
-
Haematologia 02/1996; 27(4):209-10.
-
[show abstract]
[hide abstract]
ABSTRACT: An unusual triclonal IgG combination in the serum of a 56-year old male with clinical stage IIIB multiple myeloma is reported. The patient initially had an IgG4(lambda) monoclonal protein in his serum and later developed an IgG2(kappa) and an IgG (kappa) which possessed the characteristics of both IgG1 and IgG3 subclasses with an unusual combination of allotypic markers. Three M-proteins did not share idiotypic determinants. A rare class-switch recombination followed by mutation has been considered as a possible mechanism leading to this combination.
European Journal Of Haematology 06/1995; 54(5):288-95. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A patient with acute myelomonocytic leukemia (M4), dysmegakaryocytopoiesis and thrombocytosis is presented. Immunophenotyping and blast colony assay showed the presence of blasts with IaDr, CD 33 and CD 14 antigens. Cytogenetic analysis and level of thrombopoietin were normal. This atypical case represents yet another example of the transitional zone between atypical myeloproliferative disease and acute leukemia, and the apparent absence of any cytogenetic abnormality is noteworthy.
Haematologia 02/1991; 24(2):113-6.
