Milena Todorovic

Klinički centar Srbije, Beograd, Central Serbia, Serbia

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Publications (30)39.25 Total impact

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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6(+) protein expression into BCL-6(-) expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6(-) patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6(+) and BCL-6(-) groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.
    12/2014; 30(4):269-274.
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    07/2014; 12(3):438-9.
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    ABSTRACT: Based on the results of clinical trials, there is no global consensus on the optimal first line therapy for patients with advanced Hodgkin lymphoma (HL) with both, ABVD and BEACOPP currently being used. However, the results of clinical trials are usually better than those in daily practice. We thus describe here our experience on 314 advanced classical HL patients treated with ABVD at the Clinical Center of Serbia and associated centers between 1997 and 2008. The median follow-up for all patients was 91 months; the estimated 5-year event free survival was 62% and the 5-year OS 76%. Multivariate Cox regression analysis revealed that patients with IPS≥3 and extranodal disease involving more than one site have a poorer outcome. The data presented here show on overall improvement in outcome as compared to more previous data and illustrate the problems of treating advanced stage HL outside the setting of a clinical trial.This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 05/2014; · 2.55 Impact Factor
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    ABSTRACT: Background The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). Aims The present study was designed to investigate the prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL. Methods We retrospectively analyzed the prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL patients treated with R-CHOP. Results ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59 × 109/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1 × 109/L). Low ALC, high AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these parameters were not in significant correlation with relapse rate. The patients with low ALC, “high” AMC, low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had significantly shorter EFS and OS. In multivariate analysis all tested parameters (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk factors along with “bulky” disease and IPI. Conclusion All tested parameters (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC score has a slight advantage as it allows the classification of patients into three prognostic groups. Further studies are needed to determine which of these parameters has the highest predictive value.
    European Journal of Internal Medicine 01/2014; · 2.30 Impact Factor
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    ABSTRACT: Background: Primary testicular lymphoma (PTL) is a rare and highly aggressive extranodal non-Hodgkin's lymphoma. Patients and Methods: We evaluated the clinical and histopathological features and outcomes of 10 PTL patients treated in the period of 2003-2013 with multimodal therapy (rituximab, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), intrathecal prophylaxis, irradiation of the contralateral testis) following orchiectomy. Results: Complete remission was achieved in 8 patients after first-line therapy while 2 patients had disease progression. The median follow-up duration was 30 months (range 6-110 months). Relapse occurred in 3 patients. 1 patient relapsed in the contralateral testis, while the other 2 patients relapsed to the skin and the central nervous system (CNS), respectively. The time to relapse was 2, 8, and 9 months. Patients with disease progression and relapse received ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) as salvage treatment, except for 1 patient who was treated with palliative radiotherapy. After second-line therapy, only 1 patient had a short partial remission of 2 months. The median overall survival was 48 months, and the mean progression-free survival was 36 months (the median was not reached). Conclusions: We evaluated 10 patients with PTL treated with rituximab plus CHOP, prophylactic intrathecal chemotherapy, and prophylactic irradiation of the contralateral testis, resulting in good outcome and low incidence of relapse in the contralateral testis; however, the benefit of intrathecal chemotherapy is not yet confirmed. © 2014 S. Karger GmbH, Freiburg.
    Oncology research and treatment. 01/2014; 37(5):239-42.
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    ABSTRACT: Orbital and ocular andexal Mucosa-Associated Lymphoid Tissue Lymphoma (MALT) or ocular adnexal MALT lymphoma (OAML) is the most common of all eye non-Hodgkin lymphomas. Autoimmune inflammatory disorders and chronic infections are important etiological factors and CD5 and CD43 (sialophorin) tumor markers are significant negative prognostic factors. Disease signs and symptoms can occur a long time before diagnosis. Varieties of treatment options are available. The aim of this retrospective analysis was to compare the efficiency of different treatment options and to investigate disease outcome. Twenty OAML patients, diagnosed in the Clinic of Hematology, Clinical Centre of Serbia, between 2003 and 2013, were enrolled. In most cases, OAML developed in the eighth decade with greater incidence in the male population. Median age was 67.5 years. The median period between the appearance of local signs and symptoms and diagnosis was 7 months. The dominant sign at presentation was swelling of involved tissue (40 %). The most common was orbital involvement (55 %). All patients had localized disease. Observed laboratory parameters on presentation showed low disease activity. Sialophorin prognostic significance was not registered. Our patients were initially treated differently but there was no significant difference in progression-free survival (PFS) due to initial treatment option (p = 0.2957). Median PFS was 22 months (3-89), and 5-year PFS was 60 %. Median overall survival (OS) was 43 months (1-105) and 5-year OS 95 %. Eight patients (40 %) relapsed and one patient died due to non-hematological complications. In our experience, most modern induction treatment options appear to result in the same, favorable outcome.
    Medical Oncology 12/2013; 30(4):722. · 2.14 Impact Factor
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    ABSTRACT: Special entities like solitary bone plasmocytoma (SBP) or extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with plasma cell disorders. EMP of the tongue represents very rare localization of the head and neck plasmacytoma. We report a case of 78-years-old woman who developed EMP of the tongue base detected by the magnetic resonance imaging (MRI) of the head and neck region. Immunohistochemical profile of the tumor tissue biopsy (CD38, IgG, kappa positivity) indicated diagnosis of EMP. The diagnosis was established with additional staging which confirmed the absence of other manifestation of the disease. The patient was treated with 40 Gy of radiotherapy in 20 doses resulting in the achievement of the complete remission of the disease. This case was discussed with the reference to the literature. EMP of the tongue base is a very rare entity of plasma cell dyscrasias. Appropriate irradiation results in the achievement of a long-term remission and a potential cure of the disease.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 10/2013; 70(10):972-5. · 0.21 Impact Factor
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    ABSTRACT: Treatment of blood products by riboflavin and ultraviolet (UV) light prevents of white blood cell (WBC) replication and inactivates of pathogens. The aim of this study was to determine the effects of the inactivation by riboflavin and UV light upon plasma clinical performance, based on effect on the pretransfusion international normalized ratio (INR). A prospective, controlled randomized study included 60 patients who received transfusion of plasma on the Clinic for hematology of Clinical Centre in Nis. Experimental group (EG; 30 patients) was treated with Mirasol-inactivated fresh frozen plasma (FFP) and control group (CG; 30 patients) was transfused with noninactivated FFP. Besides pretransfusion vs. posttransfusion INR, the improvement in INR patient's plasma level per one FFP unit transfused was evaluated. Total of 68 units of FFP were transfused to patients of CG (2.24±0.83 units per patient). Patients of EG received 84 units of Mirasol-inactivated plasma (i.e. 2.80±1.19 units per patient). There was significant increase in number of FFP transfusions that normalized coagulation parameters in EG compared to CG (p=0.039). Also, there was a significant improvement of INR after every FFP unit application (p=0.046). We found a linear relationship between pretransfusion INR and improvement of INR (r=0.97; p<0.001). Plasma treated with riboflavin and UV light retains hemostatic competence and can be used efficiently in the therapy of congenital or acquired coagulopathies, but in larger quantity as compared to noninactivated FFP volume.
    Transfusion and Apheresis Science 03/2012; 47(1):33-7. · 1.23 Impact Factor
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    ABSTRACT: Angiogenesis in solid tumors is important for tumor growth, invasion, and metastasis. However, angiogenesis plays also an important role in hematological malignancies. We have analyzed the expression of vascular endothelial growth factor (VEGF) in the leukemic blast cells and microvessel density (MVD) in the bone marrow biopsy samples of the patients with acute lymphoblastic leukemia (ALL). Bone marrow MVD of the patients with ALL was significantly higher compared with normal controls and complete remission (P<0.001), but slightly lower than in patients with relapsed ALL (P>0.05). The bone marrow blast VEGF expression was significantly higher in newly diagnosed ALL patients, with predominant strong VEGF expression as compared with complete remission patients (who had negative or weak VEGF expression) (P<0.05), whereas initial values were slightly lower than in relapsed patients. There was a strong positive correlation between VEGF expression and MVD at presentation of ALL. Stronger expression of VEGF on blast cells indicates shorter overall survival in ALL. Furthermore, initial values of MVD had positive correlation with overall survival and leukemia-free survival (P=0.024 and P=0.017, respectively). Our data suggest that increased angiogenesis (confirmed by immunohistochemical expression of VEGF in leukemic blasts), and MVD may play an important role in the pathophysiology of ALL with prognostic implications. Thus, targeting VEGF pathway may bring the new approach for ALL treatment-using antiangiogenic drugs and tyrosine kinase inhibitors in combination with standard chemotherapy regimens.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 03/2012; 20(5):488-93. · 1.63 Impact Factor
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    ABSTRACT: Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell transplant (SCT) in CML treatment--as a former "nearly monopolistic" therapeutic manner--is nowadays controversial. The objective of this retrospective study was to evaluate the results obtained in the treatment of CML patients, with a particular attempt to define parameters critical for clinical benefit and superior overall outcome following allogeneic SCT. A total of 32 CML patients (27 in chronic phase and 5 with advanced disease), with female/male ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN-alpha) with or without ARA-C, and additional 7 patients with no response to imatinib mesylat (IM). The time from diagnosis to SCT was approximately 12 (range 3-37) months. The patient were categorized according to the risk for the disease, transplant-related mortality (TRM) scoring system, and stem cell (SC) source. The basic conditioning regimen was a combination of busulphan and cyclophosphamide (BuCy-2). Graft-versus-host disease (GvHD) was typically prevented with cyclosporine-A (CsA) and methotrexate (MTX). Engraftment was observed in 26 (84.4%) patients, with polymorphonuclear (PMNs) and platelet (Plt) recovery on the 15th (range 10-22) and 19th (range 11-29) posttranspalnt days, respectively. Acute GvHD (aGvHD) had 13/26 (50%), and chronic GvHD (cGvHD) 10/21 (47.1%) patients. The incidence of overall TRM was 46.8% (15/32), while early death was noticed in 4 (12.5%) patients. A cause of death in 9 (28.1%) patients was cGvHD, in 2 (6.25%) patients infection, and in 3 (9.35%) cases disease-relapse was occurred. Fourteen (43.7%) of the patients are still alive, 9 from the low-risk group for TRM, with long-term survival from 1 to 16 years. Patients who received SCs from peripheral blood (PB) vs bone marrow (BM) had significantly faster engraftment (p < 0.05), lower oropharingeal mucositis rate (25% vs 70%; p < 0.05), but more frequent cGvHD (83.3% vs 30.3%; p < 0.05). A significantly improved (log-rank = 2.39; p < 0.01) overall survival (OS) was obtained in BM-setting. The results obtained in this study are in accordance with data from analogous clinical trials. Exactly, in the era of the new target therapy (TKI application), allogeneic SCT can be still a convenient therapeutic approach for well-selected CML-patients, especially for those with initial high-risk disease and lower probability of TRM.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 01/2012; 69(1):37-42. · 0.21 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the prognostic significance of international prognostic index (IPI), mantle cell lymphoma IPI (MIPI), simplified MIPI (sMIPI), and MIPI biological (MIPIb), as well as their correlation with immunophenotype, clinical characteristics, and overall survival (OS), in a selected group of 54 patients with advanced-stage mantle cell lymphoma (MCL), treated uniformly with CHOP. Seventeen patients had IV clinical stage (CS), while other 37 had leukemic phase at presentation. Diffuse type of marrow infiltration was verified in 68.5% and nodular in remainder patients. Extranodal localization (25.9%) included bowel (20.4%), pleural effusion, sinus, and palpebral infiltration. All of analyzed patients expressed typical MCL immunophenotypic profile: CD19(+)CD20(+)CD22(+)CD5(+)Cyclin-D1(+)FMC7(+)CD79b(+)smIg(+)CD38(+/-)CD23(-)CD10(-). Median OS of the whole group was 23 months, without significant differences between IV CS and leukemic phase patients. Thirty-two patients (59.3%) responded to initial treatment, 9 (16.7%) with complete and 23 (42.6%) with partial remission. Negative prognostic influence on OS had high IPI (P < 0.01), high sMIPI (P < 0.001), MIPI (P < 0.01), MIPIb (P < 0.01), extranodal localization (P < 0.01), and diffuse marrow infiltration (P < 0.01). Testing between randomly selected groups showed that patients with lower proportion of CD5(+) cells (<80%) correlated with cytological blastoid variant and had shorter survival comparing with the group with higher proportion of CD5(+) cells (>80%) (P < 0.01). Using univariate Cox regression, we proved that IPI, sMIPI, MIPI, and MIPIb had an independent predictive importance (P < 0.01) for OS in uniformly treated advanced MCL patients, although sMIPI prognostic significance was the highest (P < 0.001).
    Medical Oncology 12/2011; 29(3):2212-9. · 2.14 Impact Factor
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    ABSTRACT: BACKGROUND/AIM: Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease--aGvHD) and delayed (chronic GvHD--cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). METHODS: We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML)--39, acute lymphoblastic leukemia (ALL) 47, chronic myeloid leukemia (CML)--32, myelodysplastic syndrome (MDS)--10, Hodgkin's lymphoma (HL)- 2, multiple myeloma (MM) 3, granulocytic sarcoma (GrSa) 3, severe aplastic anemia (sAA)--22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one "Large Volume Leukapheresis" (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 microg/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (P < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT hd a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the long-term OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 12/2011; 68(12):1026-32. · 0.21 Impact Factor
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    ABSTRACT: Bacterial contamination of blood components, primarily platelet concentrates (PCs), has been identified as one of the most frequent infectious complications in transfusion practice. PC units have a high risk for bacterial growth/multiplication due to their storage at ambient temperature (20 +/- 2 degrees C). Consequences of blood contamination could be effectively prevented or reduced by pathogen inactivation systems. The aim of this study was to determine the Mirasol pathogen reduction technology (PRT) system efficacy in PCs using an artificial bacteria-contamination model. According to the ABO blood groups, PC units (n = 216) were pooled into 54 pools (PC-Ps). PC-Ps were divided into three equal groups, with 18 units in each, designed for an artificial bacteria-contamination. Briefly, PC-Ps were contaminated by Staphylococcus epidermidis, Staphylococcus aureus or Escherichia coli in concentrations 10(2) to 10(7) colony forming units (CFU) per unit. Afterward, PC-Ps were underwent to inactivation by Mirasol PRT system, using UV (lambda = 265-370 nm) activated riboflavin (RB). All PC-Ps were assayed by BacT/Alert Microbial Detection System for CFU quantification before and after the Mirasol treatment. Samples from non-inactivated PC-P units were tested after preparation and immediately following bacterial contamination. Samples from Mirasol treated units were quantified for CFUs one hour, 3 days and 5 days after inactivation. Results. A complete inactivation of all bacteria species was obtained at CFU concentrations of 10(2) and 10(3) per PC-P unit through storage/investigation period. The most effective inactivation (10(5) CFU per PC-P unit) was obtained in Escherichia coli setting. Contrary, inactivation of all the three tested bacteria species was unworkable in concentrations of > or = 10(6) CFU per PC-P unit. Efficient inactivation of investigated bacteria types with a significant CFU depletion in PC-P units was obtained--3 Log for all three tested species, and 5 Log for Escherichia coli. The safety of blood component therapy, primarily the clinical use of PCs can be improved using the Mirasol PRT system.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 12/2011; 68(12):1041-6. · 0.21 Impact Factor
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    ABSTRACT: The initial use of immunosuppressive therapy (IST) in severe aplastic anemia (sAA) or reapplication of IST-centered methods following disease relapse is successful only in well-selected patients. The potential treatment by autologous stem cell (SC) transplant in sAA is still an innovative/pioneering therapeutic approach. To our best knowledge, this is the second published case of autologous SC transplant in sAA. The aim of this work was to optimize mobilization and timing for SC harvesting - using our own controlled-rate cryopreservation - with higher CD34(+)/CD90(+) subset yield and recovery in order to obtain complete and long-term hematopoietic reconstitution following autologous SC transplant. We report a 35 year-old sAA male patient who initially underwent IST using rabbit ATG and Cyclosporine A (CsA). He was supportive transfusion dependent for the whole period of IST-phase. After the second IST-cycle, polymorphonuclear (PMN) cell count increase (>2.0 × 10(9)/L) was observed, when SC mobilization, two large volume leukapheresis procedures and following autologous transplant were performed. The yields of harvested CD34(+) and CD34(+)/CD90(+) cells were 5.75 × 10(6)/kgbm and 1.7 × 10(6)/kgbm, respectively. The quantity of applied CD34(+) and CD34(+)/CD90(+) cells in autologous SC transplant were 5.45 × 10(6)/kgbm (7-AAD(CD34)(+)(viability)=95.42%) and 1.63 × 10(6)/kgbm (7-AAD(CD34)(+)(/CD90)(+)(viability)=95.42%), respectively. Hematopoietic reconstitution registered due to second month after autologous SC transplant and he is 24 months in complete medullar, hematological and clinical remission, with normal cytogenetic status - applying only continuous CsA therapy. The results obtained strongly confirm that in sAA, with no allogeneic SC donor, autologous transplant can result in a successful clinical outcome. We suggest that CD34(+)/CD90(+) subset count in peripheral blood and/or cell-harvest could be more valuable predictive factor than total CD34(+) quantity of optimized collection-timing and superior treatment efficacy of autologous SC transplant in sAA.
    Transfusion and Apheresis Science 08/2011; 45(2):137-41. · 1.23 Impact Factor
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    ABSTRACT: A 60-year-old woman with no previous history of chronic disease or malignancy presented with intense back and left leg pain and sleep disturbances. The patient had been treated unsuccessfully for the past 6 months with analgetics. Magnetic resonance imaging showed a soft tissue tumor in the L5-S1 region that involved the spinal canal, and a pathohistological analysis of the tumor specimen confirmed the presence of non-Hodgkin, diffuse large B cell lymphoma. After the diagnosis was confirmed, malaise, nausea, and vomiting developed. Multislice computed tomography of the endocranium showed focal infiltration of the hypothalamus and lateral ventricle; dissemination of a systemic lymphoma was excluded. Therapy was initiated as per the De Angelis protocol. After intravenous and intrathecal administration of metotrexate, the patient developed signs of central diabetes insipidus, which responded to therapy with an antidiuretic hormone analog. Despite the obvious infiltration of the hypothalamus, we cannot exclude an idiosyncratic effect of methotrexate on the central diabetes insipidus.
    Neurological Sciences 08/2011; 33(2):387-90. · 1.41 Impact Factor
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    ABSTRACT: The clinical course of patients with follicular lymphoma is variable from a slowly progressive disease to a progressive disease with a survival time of approximately 1 year. Many prognostic models have been suggested to identify high-risk patients. Recent gene profiling analysis showed that the clinical behavior of follicular lymphoma is determined by the properties of the nonmalignant tumor microenvironment. We investigated the role of lymphoma-associated macrophages (LAMs) in tumor tissue in patients with newly diagnosed follicular lymphoma. The LAM was determined immunohistochemically in lymph node tissue sections by anti-CD68 PG-M1 and analyzed through high-power field (HPF) magnification intrafollicularly (IF) and extrafollicularly. In our study, the patients who had an IF LAM count equal to or more than 10/HPF had significantly shorter overall survival (P=0.018) and 3 years of progression-free survival (P=0.034) compared with patients with <10 LAM/HPF. Multivariate analysis indicated that IF LAM/HPF ≥ 10 and Eastern Cooperative Oncology Group performance status >1 are independent prognostic factors for a poor outcome.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 07/2011; 20(1):41-6. · 1.63 Impact Factor
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    ABSTRACT: Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus--SLE, 11 rheumatoid arthritis--RA, 12 Sjögren's syndrome--SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)--P < 0.05. The most frequent lymphoproliferative neoplasms were non-Hodgkin's lymphoma--NHL (35/40; 88%), diffuse large B-cell lymphoma (DBCL)--12 (34%), follicular lymphoma (FC)--7 (20%), small lymphocytic (SL), and marginal zone lymphoma (MZL)--5 (14%) each. The primary site of NHL was extranodal in 18/35 (51.5%) cases. Advanced disease on diagnosis (III + IV clinical stages), constitutional symptoms, and bulky disease were diagnosed in 27/35 (77%), 26/35 (74%), and 3/35 (8.5%) patients, respectively. The overall survival (OS) was as follows (months): DBCL-12, FC-63, SLL-60, and MZL-48. There was no association between the lymphoproliferative neoplasm histological subtype and the systemic autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting.
    Medical Oncology 07/2011; 29(3):2207-11. · 2.14 Impact Factor
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    ABSTRACT: Plasmablastic lymphoma (PBL) has initially been described as a rapidly progressive and almost invariably fatal diffuse large-cell lymphoma with plasmablastic features, exclusively involving the jaw and oral mucosa in HIV-positive patients. Although its clinical features may help in differential diagnosis, an extra-oral localization in a patient without HIV makes it more difficult to suspect clinically. We describe a very rare case of gastric PBL primarily involving stomach in a middle age man without an HIV infection. A biopsy was performed and its findings revealed a diffuse, monomorphous proliferation of the tumor cells with features of immunoblasts, MUM-1, EMA, and lambda light chains positive. Serology was negative for the human immunodeficiency virus (HIV), HBsAg, and hepatitis C virus infection. The patient started treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, but unfortunately died before the second cycle was given. To our knowledge, this is the second case of gastric PBL presented in HIV-negative patients. The findings in this case suggest that PBL should be included in the differential diagnosis of gastrointestinal tumors.
    Medical Oncology 04/2011; 29(2):1186-9. · 2.14 Impact Factor
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    ABSTRACT: Anti-A/B depletion efficacy and clinical outcome for 22 ABO-incompatible kidney transplants were investigated. Preconditioning by anti-CD20 therapeutic plasma exchange (TPE) by Cobe-Spectra (CaridianBCT USA) and simplified extracorporeal immunoadsorption (ECIA) as well as triple immunosuppression (tacrolimus/mycophenolate-mofetil/steroid) were performed. The use of TPE with ECIA resulted in a high in vivo anti-A/B depletion, 94.23±4.2% for IgG and 95.26±3.2% for IgM. The mean anti-A/B titers on day 0 were: IgG=1.27±1.03 and IgM=2.20±1.47. One HLA cross-match positive patient (beside ABO-incompatibility) subjected to double-dose anti-CD20 and intensive TPE-treatment had no allograft rejection. The level of serum creatinine ranged from 100 to 156 μmol/L in the entire group of patients during postoperative follow-up (up to 36 months). One recipient (with sepsis and multi organ distress syndrome) lost kidney function in early posttransplant period. ABO-incompatible (n=2) and ABO-compatible (n=3) kidney recipients had severe anemia and bleeding episodes. They were efficiently treated using original "multi-manner" apheresis. Our study represents a clear demonstration that the combination of TPE with ECIA and anti-CD20 is effective in anti-A/B depletion. This therapeutic approach is feasible in clinical setting showing satisfactory short-term results although verification of long-term effects needs to be confirmed in a larger study. The rapid beneficial outcome of "multi-manner" apheresis strongly supports the future use of this therapeutic modality for efficient oxygenation and advanced engraftment.
    Transfusion and Apheresis Science 10/2010; 43(2):141-8. · 1.23 Impact Factor

Publication Stats

60 Citations
39.25 Total Impact Points


  • 2007–2014
    • Klinički centar Srbije
      • Institute of Haematology
      Beograd, Central Serbia, Serbia
  • 2012
    • Harvard Medical School
      Boston, Massachusetts, United States