Rituximab in the therapy of stage III and IV follicular lymphoma: Results of the REFLECT 1 study of the Serbian Lymphoma Group.

PURPOSE: Follicular lymphoma (FL) is an indolent lymphoma that responds well to rituximab+chemotherapy. We evaluated the prognosis and efficacy of immunochemotherapy in patients with previously untreated, advanced FL. METHODS: REFLECT 1 is a multicentre, prospective study of 99 patients with previously untreated FL stage III-IV. All patients were treated with rituximab+chemotherapy x 6 cycles, plus 2 cycles of rituximab monotherapy. Clinical assessment was performed at baseline, after completion of the first 6 cycles of therapy and every 3 months from the end of immunochemotherapy to the end of the study period. RESULTS: Eighty-nine out of 99 patients with complete documentation were included. Complete remission (CR) was achieved in 61.6%, partial remission (PR) in 11.6% and progressive disease (PD) in 24.4% of the patients. Time to progression (TTP) and overall survival (OS) after the 1st, 2nd and 3rd year were 89.9, 72.7, 57.8%, and 94.2, 92,6 and 92.6%, respectively. The probability of achieving CR was significantly lower in the high risk group according to Follicular Lymphoma Prognostic Index (FLIPI) score. Expression of CD43 antigen had a significant impact on the probability of 2-year TTP and OS, and ECOG performance status had a significant impact on OS. CONCLUSIONS: Treatment with rituximab plus chemotherapy is effective in advanced stages of FL. Significant prognostic factors are FLIPI score for induction therapy outcome, CD43 antigen expression for OS and TTP and ECOG performance status for OS.

BCL10 aberations and NF-kappa B activation involving p65 are absent or rare in primary gastric MALT lymphoma.

BACKGROUND/AIM: Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 5-17% non-Hodgkin lymphomas (NHL). The molecular pathogenesis of MALT lymphomas is not well-established. The aim of this study was to evaluate immunohistochemically determined nuclear coexpression of BCL10 and NF-kappaB (NF-kappaB) in tumor cells of gastric MALT lymphoma and its impact on the patogenesis and outcome of the disease. METHODS: Medical records of 35 patients with newly diagnosed gastric MALT lymphoma were analyzed and biopsy specimens were immunostained for BCL10 and NF-kappaB expression (p65 subunit). RESULTS: The median age of 35 patients diagnosed with gastric MALT lymphoma was 63.5 years (male/female = 21/14). Symptoms were present in 23/35 (65.7%) patients with the weight loss as the most common symptom. Gastric MALT lymphomas were usually localized in the stomach corpus and corpus and antrum (45.7% and 31.2%, respectively). H. pylon infection was confirmed in 20 out of 30 (66.7%) patients. Treatment options were as follows: immunochemotherapy in 10 (28.5%) patients, surgery in 9 (25.8%) patients, combined surgery and chemotherapy in 14 (40%) patients and supportive measures in 2 (5.7%) patients. Complete remission was achieved in 13 (37.10/) patients and partial remission in two (5.7%/) patients. Sixteen (45.7%/) patients had disease progression (p < 0.001). Cytoplasmatic expression of BCL10 in tumor cells was detected in 19 (54.3%) specimens. Nuclear expression was detected in no specimen. Cytoplasmic expression of NF-kappaB was present in 22 (65.7%) specimens, but nuclear expression was not detected in any specimens. CONCLUSION: Nuclear expressions (activation)of NF-kappaB p65 subunit and BCL10 were not detected in specimens of gastric MALT lymphoma. The correlation of nuclear coexpression of BCL10 and NF-kappaB in gastric MALT lymphoma was not established. These results indicate that other mechanisms and signal pathways are active in lymphogenesis of gastric MALT lymphoma, as that apoptotic inhibition is not the main, nor the only mechanism in tumorogenesis.

Comparison of prognostic impact of absolute lymphocyte count, absolute monocyte count, absolute lymphocyte count/absolute monocyte count prognostic score and ratio in patients with diffuse large B cell lymphoma.

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 0.59×10(9)/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1×10(9)/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.

[Late onset of severe thrombocytopenia during interferon treatment for chronic hepatitis C infection--case report].

INTRODUCTION: Thrombocytopenia is a common finding in chronic liver diseases and it is caused by different pathophysiological mechanisms. Immunologic thrombocytopenic purpura (ITP) in hepatitis C infection is a distinct clinical entity. Possible reasons for ITP in this case could be capabillity of HCV to induce autoimmune phenomena but also immunomodulatory effects of interferon that is used for HCV infection treatment. The specific laboratory parameters for ITP diagnosis during HCV infection have not been defined yet. CASE OUTLINE: A 37-year-old patient diagnosed with HCV infection was treated with PEG-interferon and Ribavirin during 24 weeks. The partial response was achieved after the therapy with reduction of viral replications. One month after therapy completion, the patient was hospitalized due to skin haemorrhagic syndrome and a serious degree of thrombocytopenia (2 x 10(9)/l).The number and megakaryocyte morphology in bone marrow aspirate were normal. An assay of thrombocyte kinetics by radioactive marker (Indium 111) showed rapid thrombocyte destruction and their early sequestration in the spleen. CONCLUSION: Results of assays about thrombocyte kinetics during HCV infection show enchanced thrombocyte destruction in the liver. Accordingly, the most important parameter for ITP diagnosis in HCV infection, in this case, was rapid thrombocyte destruction and their early sequestration in the spleen approved by Indium kinetics. Also, in support of ITP is the increment ofthrombocyte number during therapy with intravenous immunoglobulins. Thrombocytopenia was developing during antiviral therapy and on indirect conclusion is that viral replication is not the reason for it.