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Background: Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) (formerly termed enteropathy-associated T cell lymphoma, type II) is an extremely rare peripheral T-cell lymphoma that involves the malignant proliferation of a T- lymphocyte in the gastrointestinal tract. Over time, these T cells commonly spread throughout the mucosal lining of a portion of the GI tract (particularly the jejunum and ileum of the small intestine), lead to GI tract nodules and ulcerations, and cause symptoms such as abdominal pain, weight loss, diarrhea, obstruction, bleeding, and/or perforation. Its clinical, morphologic, and immunophenotypic features distinguishing it from the more common Enteropathy Associated T-Lymphoma (previously EATL type I) made it a separate entity. Case report: We present a case of a rare extremely aggressive T cell lymphoma that originates from the gastrointestinal tract, spreads to surrounding organs and is refractory to surgery and chemotherapy. We describe а case report of 79 years old patient with clinical features of acute abdomen, ileus, treated with surgery two times. During the first surgery partial resection of jejunum was performed. Pathohistology and immunоhistochemistry findings of MEITL. PET/CT scan revealed infiltration of intestinum, uterus, ovarium. During the second operation partial resection of ileum and hysterectomy with adnexectomy was performed. The patient is treated with antracycline-based regimen CHOP21 (4 cycles). Re-evaluation with second PET/CT scan revealed residual tumor on the intestinum and bladder. The patient deteriorate with acute renal failure and multi-organ failure. Despite aggressive treatment with extensive surgery and aggressive anthracycline-based chemotherapy, in a short time the tumor spread to surrounding organs (sigma, bladder). The patient survived 11 months from the initial definitive diagnosis. Conclusion: MEITL is a challenging primary intestinal T cell lymphoma to treat as the outcome is frequently poor despite surgery and chemotherapy. Most patients are elderly with co-morbidities and they usually present late rendering any therapy ineffective. Young age, early Ann-Arbor/Lugano disease stage, good performance scale status, patients receiving autologous stem cell transplantation and less bulky disease are associated with an improved survival outcome. Further research is needed to incorporate new therapeutic modalities based on molecular research for successful treatment of this aggressive lymphoma.

BACKGROUND: Allogeneic stem cell transplantation (ASCT) is a potentially curative therapeutic approach in patients with intermediate and high-risk myelodysplastic syndrome (MDS). If a family sibling or unrelated donor is not available mismatched donors are viable option for young patients with no comorbidities. The aim of this case presentation was to evaluate our first experience with haploidentical transplantation for this indication. CASE PRESENTATION: We present a case of 50 years male patient with myelodysplastic syndrome (MDS) diagnosed at University Clinic for hematology, Skopje, North Macedonia. Patient was scored in IPSS -R as high risk patient. He was referred for HLA DNA typing of family siblings and since he didn’t have identical sibling and unrelated donor, he was referred to continue treatment with haploidentical stem cell transplantation. He received Flu Bu conditioning and PTCY, cyclosporine and MMF for GVHD prophylaxis. Peripheral blood stem cells (PBSC) from his mismatched brother were infused in the amount of CD34=5.8x106/kg. He experienced prolonged engraftment, severe infective bacterial infections and CMV reactivation with clinical manifestation of CMV colitis. He was successfully treated with antiviral drug and completely resolved. His bone marrow analysis showed complete remission and chimerism evaluation revealed high donor engraftment. Patient is now +34 months post transplant in complete remission. CONCLUSION: The use of a mismatched donor increases the risk of NRM, but there is also evidence to suggest that an haploidentical donor is a valid choice, as general outcome appears to be at least similar to MUD.

SARS-CoV-2; Hematological malignancies SARS-CoV-2; Neoplasias hematológicas SARS-CoV-2; Neoplasies hematològiques Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States, Grant/Award Number: Project 2020-8223.

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Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.

BACKGROUND: Erdheim Chester disease (ECD) is a rare form of non-Langerhans histiocytosis that still presents a diagnostic and clinical dilemma. CASE PRESENTATION: We present a rare case of ECD, young 31 male with atypical localisation and soft tissue presentation and no bone involvement. He started clinical investigations due to subcutaneous tumour mass in the lumbar spine that caused severe back pain. Skin biopsy revealed ECD with Immunohistochemistry CD68+, CD10+, CD11c+, vimentin+, S100A4+. Activating BRAFV600E mutation was positive from the tumour tissue. The patient was referred to the haematology department. PET CT was performed for initial disease staging. Treatment was started with corticosteroids (methylprednisolone 0.5 mg/kg per day), and after 7 days, a significant clinical improvement was noticed in terms of pain disappearance with no need for pain killers. After two weeks, treatment with interferon Alfa (IFN-α) was started in a dose of 3 million units 3 times per week. After 4 months of interim treatment PET, CT revealed a significant reduction of the tumour mass. Therapy with IFN-α was continued, and the patient is still clinically in good condition. CONCLUSION: It can be concluded that shortening the time of diagnosis of ECD is essential in treatment outcome of this disease. Still, large studies have to confirm the best treatment of this rare condition.

Posterior reversible encephalopathy syndrome (PRES) is one of the most serious complication after allogeneic stem cell transplantation in paediatric setting. It is most commonly reported as adverse event of immunosuppressive strategies during transplantation. We present a case of a 7 years old girl with myelodysplastic syndrome (MDS) treated with allogeneic stem cell transplantation (ASCT) at our department. Diagnosis of PRES was confirmed by imaging techniques during the first month after transplant and it was very likely connected with cyclosporine neurotoxicity. The aim of this article is to present our first experience in diagnosing and treating PRES in paediatric stem cell transplantation. Our experience showed that PRES is one of the reasons for higher transplant related mortality in children. Early prediction of factors contributing to PRES and closely monitoring of patient’s vital signs, especially blood pressure, neurological status and vision are the main contributors for challenging the patient with another immunosuppressive agent that has less neurological toxicity. Still studies have to be initiated to confirm the influence of PRES on transplant outcome.

Introduction. Autoimmune diseases are a family of more than 100 heterogeneous conditions that affect 5 to 8% of the world’s population. The etiology is still un-known but the disregulation of the regulatory T-lymphocytes play a central role inthe autoimmunity and the success of the long-term remission. Although conventional immunosuppression and new biological agents can provide disease control in severely affected patients, such treatments are rarely curative and alternative strategies are needed. Indeed, severe forms of systemic autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immune cytopenia (HIC) and Crohn’s disease are difficult to be treated. High-dose immunosuppressive therapy followed by autologous stem cells transplantation is reliable option for a successive treatment of this group of patients. Aim. To determine the safety of the procedure of autologous stem cell transplantation in patients with autoimmune diseases and concomitant malignant hematological disorders. Methods. During a period of 15 years (from September 2000 to September 2015) at the University Clinic of Hematology in Skopje we have treated 6 patients with autoimmune disease and concomitant hematological neoplasm. None of the patients was treated for primary autoimmune diseases. Two men and 4 women, with median age of 47 years were treated. Sjogren syndrome and multiple myeloma were found in 2 patients, polyartheritis nodosa and multiple myeloma in 1 patient, rheumatoid arthritis and acute myeloblastic leukemia in 1, systemic lupus erythematosus and non-Hodgkin lymphoma in 1; severe psoriasis and acute myeloblastic leukemia in 1 patient. Results. All treated patients are alive after trans-planted procedure, with transplant related mortality day +100: 0. Conclusion. Autologous stem cell transplantation is safe and recommended option for treatment ofpatients with autoimmune disease and hematologic neoplasm.

Introduction. Acute myeloid leukemia (AML) represents an entity well defined among the hematological malignnant diseases from diagnostic and therapeutic point of view. Still, big concern remains for those patients where the induction therapy fails. Classified in the group of refractory AML these patients are with poor prognosis. There are numerous attempts in providing the best surviving results by administration of appropriate therapy. Our center presents its experience in treating patients with refractory AML by administration of FLAG-Ida regimen, followed by hematopoietic stem cell transplanttation, autologous or allogeneic, depending on the availability of HLA matched sibling donor of hematopoietic stem cells. Methods. In patients with refractory AML, administering FLAG-Ida chemotherapy we have achieved complete remission in 22 patients (47%). Average age of the treated group of patients was 36.6 years (17-53). All of them proceeded to high-dose chemotherapy and underwent hematopoietic stem cell transplantation (HSCT). We performed autologous HSCT in 13 patients, and allogeneic HSCT in 9 patients. Median time to HSCT was 6.6 months (4-10), and in most of the patients we used myeloablative conditioning (MAC). Results. The disease-free survival in our group of patients is 74 months (22-148). The longest overall survival was 148 months and was registered in a patient with allogeneic sibling HSCT. We can conclude that FLAG-Ida regimen is an appropriate and suitable salvage chemotherapy protocol for patients with refractory AML especially when it is used in the context of preparation for HSCT.

Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: –α3.7 (rightward), –(α)20.5 and – –MED I deletions and Hb Icaria [α...

The article presents a case with diagnosed Hodgkin disease (HD) during pregnancy. The aim of this case study was to present diagnostic possibilities in determining HD stage during pregnancy and therapeutic dilemmas. The incidence of HD during pregnancy is 3.2% of all cases with this malignant hematological disorder. The treatment of this disease during pregnancy depends on disease-related factors, pregnancy-related factors, as well as possible implications for fetal morbidity and mortality. The need of analysis of the nature of the disease during pregnancy indicates examination of a larger series of pregnant women with HD and the drawn conclusions affect the decision whether chemotherapy treatment should start immediately or it should be postponed for after delivery.

Background. Peripheral blood stem cells (PBSC) have largely replaced conventional, unprimed bone marrow (BM) as source for autologous transplantation. Aim. To present the mobilizing strategies in patients with lymphoproliferative diseases taking in consideration demographic and treatment related variables that have influence as prognostic factors. Material and Methods. The study was accomplished with patients treated with autologous transplantation at University Hematology Hospital, Skopje, and Republic of Macedonia during 5 year period. A total of 70 patients with lymphoproliferative diseases were included in this study. Results. Patients transplanted with PBSC, compared with patients transplanted with BM showed p

Background. Myelodysplastic syndrome (MDS) as a complex disorder comprised of 7 entities may arise as a primary disorder, or in a setting of an underlying disease, or as therapy related (secondary MDS). Some cases show MDS/EVI1 gene fusion, and some studies have pinpointed the association between the high-risk MDS and increased telomerase activity. Aim. To determine the frequency of MDS/EVI1 gene fusion in cases of primary MDS, and to evaluate the possibility for detection of increased telomerase activity in peripheral blood samples from patients with MDS. Material and methods. We isolated DNA from 35 bone marrow biopsies, and measured the blood telomerase activity (RTA) in 21 of the patients. We performed immunostainigs for Ki-67, Bcl-2 and p53 on the biopsy samples in order to test the correlations to the RTA and MDS/EVI1 presence. MDS/EVI1 fusion was detected with touch-down-direct PCR, and RTA was measured using the “TeloTAGGG-PCRELISA-plus kit”. Results. We found MDS/EVI1 fusion in 17.39% of high-risk MDS cases (overall 11.43%). RTA was highly variable in the analyzed group, with 1,8 fold increase of the mean RTA compared to the controls. It was due to the significant RTA increase in high-risk MDS cases, compared to the low-risk cases (p

Background. According to immunological deficit the period after hematopoietic stem cell transplantation (HSCT) can be divided in three phases: aplastic phase, phase of acute GVHD, and phase of chronic GVHD. Fungal infections are predominant in first, aplastic phase. Deep neutropenia and implantation of central venous catheter are two major risk factors contributing to infection. Aim. To retrospectively analyze fungal infections, fungal isolates and to compare success of different antifungal strategies during the first 30 days after HSCT. Material and methods. During a 7 year period (2000-2007), we have performed 128 HSCT in 120 patients with different hematological diseases. Male: 62 Female: 58. Median age: 34 years. Patients were treated in sterile room, conditioned with HEPA filters, and low microbes diet. Antifungal prophylaxis with Fluconazole 200mg, Itraconazole 200mg, or combination Fluconazole200/Itraconazole 200 (in high-risk patients) was administered from day 0 until day +100. Results. Patients treated with combination of Fluconazole200/Itraconazol200 have had only few oropharyngeal candidiasis, without signs of invasive fungal infection. There is no statistically significant difference between the prophylaxis with Fluconazole and Itraconazole, (p=0,302). Non-Albicans Candida is predominantly isolated funga (Non-Albicans Candida vs. Candida Albicans: 54% vs. 46%). There is no isolation of Aspergillus during the first phase after HSCT in our group of patients. Concluson. The rising incidence of invasive fungal infections and the currently problematic early diagnosis call for an intensive exploration of new drugs and further developments in diagnosis and treatment of invasive fungal infection.

e19502 Background: Autologous stem cell transplantation (ASCT) improves survival in patients with myeloma and lymphoma but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and overall survival (OS) in patients undergoing ASCT. Methods: We analyzed outcomes of 220 patients after high-dose melphalan and high –dose anti lymphoma chemotherapy during year 2000 to 2015. Individual comorbidities were prospectively collected at the time of ASCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. Results: HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subject’s score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohorts). One-year NRM was low at 2% (95% confidence interval, 1% to 4%). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Factors that affect OS in the autologous recipients among lymphoma and myeloma patients were: HCT-CI, Karnofsky score, number of CD34+ cells/kg and time from diagnosis until transplant (p

Background: Infections are frequent cause of further morbidity and mortality in stem cells recipients. Infection-related mortality is mainly due to severe bacterial sepsis, pneumonia and fungal infections. Case Report: We report a 60 years old patient with AML. In the complete remission he is received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. The patient was treated in sterile room, conditioned with HEPA filters. Antibiotic prophylaxis regimen consisted Ciprofloxacin 1.0 gr/day, Itraconazol 400 mg/day, Acyclovir 1500 mg/day, and Immunoglobulins IV 0.1 mg/kg once per week. From day +5 patient became febrile (Ne

The aim of this study was to examine the gene frequencies of 16 KIR genes and pseudogenes ( KIR2DL1 , KIR2DL2 , KIR2DL3 , KIR2DL4 , KIR2DL5 , KIR3DL1 , KIR3DL2 , KIR3DL3 , KIR2DS1 , KIR2DS2 , KIR2DS3 , KIR2DS4 , KIR2DS5 , KIR3DS1 , KIR2DP1 , and KIR3DP1 ) and KIR genotypes in Macedonian patients with haematological malignancies, to compare them with the corresponding frequencies of healthy Macedonians and to analyse eventual association of specific genes or genotypes with the studied haematological diseases. The study included 63 patients of which 40 had acute myeloblastic leukaemia (63.5%), 11 (17.5%) had chronic myeloid leukaemia, 8 (12.7%) acute lymphoblastic leukaemia, 2 (3.17%) non-Hodgkin Lymphoma, 1 (1.59%) aplastic anemia, and 1 (1.59%) chronic lymphocytic leukaemia. Comparison of KIR gene frequencies between the 63 patients and healthy Macedonians reveals statistically significant difference for KIR3DL2 (F= 1 in the control group, and 0.95 in the patients group, p=0.001). Another statistically significant difference was observed for the frequency of Bx3 and Bx439 genotypes both found more often in patients group (P=0.017 and P= 0.009, respectively). Further analysis, involving larger series of patients and targeted at the ligands of the KIRs are needed in order to determine a certain KIR gene and/or genotype as either predisposing, or protecting factor for haematological malignancy in patients from Republic of Macedonia.

Aim: The aim of this study was to examine the gene frequencies of 16 KIR genes and pseudogenes and KIR genotypes in Macedonian patients with transplanted bone marrow and their sibling donors in treatment of haematological malignancy, and to analyse eventual association of the gene content with the occurrence of a graft versus host disease (GVHD). Material and Methods: The study was performed on 24 patients and their HLA-matched sibling donors. Results: Comparison of KIR gene frequencies between the total 24 donors and healthy Macedonians reveals statistically significant difference for KIR2DS1 (F= 0.481 in the controls group, and 0.76 in the patients group, p=0.004). This significance is even higher when the frequency of KIR2DS1 in controls is compared with the frequency in donors from pairs with GVHD (F= 0.923, P= 0.002). Another significant difference was observed for the frequency of the full-length allele of KIR2DS4*001-002, present in 25.2% of the control individuals, but in as much as 81.8% of the recipients of haematopoietic stem cell (P=0.0005). We did not see any statistically significant difference in distribution of the C1/C1, C1/C2 and C2/C2 groups among GVHD pairs. Conclusion: Our results address the difference between the haematopoietic stem cell transplantation settings with sibling and unrelated donors and suggest that the KIR2DS4*001/002 might be a predisposing factor for severe GVHD in sibling HSCT.

8023Background: Considering the high prevalence of comorbidities in multiple myeloma (MM) patients, comorbidity has an important issue for the management of myeloma. However, the impact of comorbid...

Nowadays, goal of treatment approach in diffuse large B cell lymphoma is cure and first step towards it is to achieve complete remission. DLBCL is a potentially curable disease, with curability highly dependent on clinical and biological features. According to the WHO classification of Hematological Malignancies, the entity of DLBCL is characterized by rapidly growing mature B cell tumors with large or relatively large cells and /includes a number of disease variants/entities / encompassing several distinct clinopathologic diseases, several different histologic variants and clinical subtypes. There is no unique treatment for all patients with diffuse large B cell lymphoma. Different subgroup of patients with DLBCL needs different treatment. In the pre-rutuximab era International Prognostic Index (IPI) was considered to be the most important prognostic factor for survival and the strongest indicator for identification of high-risk patients, who are unlikely to be cured with standard chemotherapy. Having in mind that IPI is based on 5 clinical characteristics (age, performance status, stage, extranodal involvement, LDH level) and it is constructed in the pre-rituximab is clear that R-IPI should be tested in rituximab era to provide any information of its validity. We retrospectively analyzed unselected population of 80 patients with confirmed diagnose of diffuse large B cell lymphoma treated at University hematology department in the period of 2005-2010. All patients were uniformly treated with R-CHOP regiment as initial treatment with curative intent. There were 80 patients with mean age 54, 5 years (15-84), male 35 and female 45. Older than 60 years were 29 patients (36, 25%). More than half of the patients (42) were diagnosed in advanced stage of the disease. We analyzed five prognostic factors: age, performance status, stage, extranodal involvement, LDH level and through the multifactorial analyses we selected two groups of patients. One with 0 to 2 factors as patients with low risk. Patients with more than 3 factors are considered as high risk. There is statistically significant difference in overall survival between two groups with five –years overall survival 70% for low risk patients and 47% for high risk. High-risk patients may be candidates for autologous transplantation as initial treatment, having in mind that in the rituximab era relapses occur very early in the first year and are difficult to be treated. R-IPI score is significant predictor and should be used for risk stratification of patients with aggressive B-cell lymphoma. However, these findings should be validated prospectively in an independent population of patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 4595 Despite advances in our understanding of its pathogenesis, acute myeloblastic leukemia remains difficult to treat. Although initial complete remission can be achieved in a high percentage of patients, relapse occurs in 70–80% of the patients. Two main approaches have been the attempt to eradicate the leukemic clonal cells population via chemotherapy with or without autologous stem cell rescue or to pursue a combined approach using an antileukemic therapy combined with an antileukemic immune response via allogeneic bone marrow transplantation. Autologous transplantation compares favorably against allogeneic bone marrow transplant in several ways. Autologous transplantation can be used as a consolidation therapy in the older population, and lack of a matched donor does not preclude the patients from this treatment. We report a retrospective analysis on 48 patients diagnosed with de novo AML, who did not have an available histocompatible donor, and who underwent autologous transplantation between years 2000–2009 at the University hematology Clinic, Skopje, Macedonia. All patients had ECOG score 1 or less. The patient's age ranged from 17 to 65 years with the median age 41 years. There were 26 males and 22 females. For stem cell mobilization patients received chemotherapy or chemotherapy plus G-CSF. The preparative chemotherapy regimen prior to autologous transplantation consisted of BuCy in 24 patient, BEAM in 22 and BuCyMel was used in the remaining 2 patients. We used bone marrow as primary source of stem cells in 18 patients, and peripheral blood stem cells in remaining 30 patients. The five years overall survival was 52% and the 5 years disease progression free survival were 42%. We analyzed sever factors that can influence the overall survival and the disease free survival such as: age, disease status, stem cell source, chemotherapy regiments prior to transplantation, conditioning regiments, number of mobilized stem cells. Advanced age and bone marrow stem cell source seems to be more influent factors. We report that the clinical results of autologous hematopoietic stem cell transplantation are sufficiently encouraging to warrant future trials that include autologous transplantation as an option for appropriately selected patients with AML in CR1. We conclude that autologous hematopoietic stem cell transplantation is a reasonable and save intensive consolidation for patients with acute myeloblastic leukemia who do not have a suitable HLA–matched donor. Disclosures: No relevant conflicts of interest to declare.

Autoimmune cyclical neutropenia is a rare syndrome with periodically severe but temporary neutropenia with occurrence of 3–4 weeks, but not rarely in 2 or 5 week intervals. Antibodies with specificity for the neutrophils has been demonstrated in a number of different neutropenic disorders and is often associated with systemic autoimmune disease. Since the role of monoclonal antibodies in the treatment of autoimmune disorders is not clearly optimized, we evaluated the effectiveness of Rituximab in the treatment of immune neutropenia. We present two cases (male 66 years and 42 years female) with immune neutropenia, associated with systemic autoimmune disease, Chron’s disease in male patient and rheumatoid arthritis in female patient. Bone marrow biopsy revealed reduction of granulopoesis and absence of neutrophils in the peripheral smear-agranulocytosis. Immunological investigations revealed increased polyclonal IgG, positive indirect granulocyte immunofluorescence test. Both patients had a clinical course with continuously intermittent neutropenia every 2 weeks, presented with recurrent febrile episodes and serious lower respiratory tract infections. Treatment with G-CSF was immediately started in both patients to reach neutrophil recovery, but after one year of periodically persistent neutropenia it was decided to start treatment with Rituximab, an infusion with standard single agent 375 mg/m2 weekly for 4 weeks. After 4 infusions neutrophils reached normal levels and the treatment continued with every 2 weeks infusion of monoclonal antibody in duration of 2 months and now once a month as maintenance treatment. The patients are one year and six months after beginning treatment with monoclonal antibodies, in stable clinical and laboratory condition. We can conclude that B cells play a central role in the autoimmune process and Rituximab treatment has been used in patients with autoimmune neutropenia. Further randomized studies will define optimal role of Rituximab in the treatment of autoimmune diseases.

Aggressive Non-Hodgkin lymphoma (NHL) is heterogeneous group with respect to clinical, histopatological and evaluative features. The International Prognostic Index (IPI) has provided a widely accepted prognostic set of criteria to design therapy. However, IPI dose not determine whether routine phenotypic features, beside IPI, may influence survival. We evaluate the prognostic significance of Bcl-2 and Ki67 protein expression in relation to clinical presentation and outcome. In the period 1989–2002,two hundred eleven patients with newly diagnosed aggressive NHL were recorded in our Department. In this study we included patients with available biopsy sample. Protein expression was analyzed on paraffin embedded tumor tissue by imunohistochemistry in relation to clinical factor and outcome. The expression of more than 20% of neoplastic cell was considered positive for bcl-2, and more than 60% for Ki-67. Comparison was made by x2 test. Survival curves were considered by Kaplan-Meyer method and compared by the long-rank test. Sixty seven patients were recorded and their characteristic were: median age 53 years, stage III and IV, 67%; present B symptoms 44%,; bone marrow infiltration 29%, elevated LDH 58%, performas status more then 1– 26%; extra nodal sites more than 2 –34%. All 62 patients received antracyclin based combination chemotherapy, 72% CHOP regiment. Overall survival was 52% with a follow up 6–183 months. Bcl-2 expression was observed in 35,5% (22pts) and Ki67 positivity over 60% in 20 pts (30%). Overall survival was influenced by bcl-2 and Kli67 expression. Bcl-2 positive cases were significantly associated with lower overall survival (20% vs. 58%; p Bcl-2 and Ki67 monoclonal antibody immunostaging appears to be a simple and reproducible method of determining biological potential of tumor cells and provides useful prognostic information in patients with aggressive NHL.