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SIGNIFICANCE OF CXCR3 EXPRESSION IN GASTRIC LOW-GRADE B-CELL LYMPHOMA OF MUCOSA-ASSOCIATED HIGH-RESOLUTION GENOME WIDE-DNA PROFILING IN MARGINAL LYMPHOID TISSUE TYPE FOR PREDICTING RESPONSIVENESS TO A. Rinaldi1, I. Kwee1, P. M. Rancoita1, M. Ponzoni2, G. Bhagat3, U. Novak3, H. Yamamoto1, T. Nakamura2, K. Matsuo3, M. Tajika2, H. Kawai2, N. Ohmiya4, V.V. Murty3, S.V. Nandula3, G. Gaidano4, R. Marasca5, M. Mollejo6, F. Facchetti7, S. Dirnhofer8, L. Baldini9, V. Gattei10, V. Canzonieri10, A. Gloghini11, J. Soulier12, 1Department of Pathology and Clinical Laboratories, Nagoya University Hospital, C. Thieblemont12, F. Forconi13, G. Pruneri14, A. Carbone11, C. Doglioni2, Nagoya, Japan, 2Department of Endoscopy, Aichi Cancer Center Hospital, M.G. Tibiletti15, E. Zucca1, M.A. Piris6, R.D. Gascoyne16, R. Dalla Favera3, Nagoya, Japan, 3Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan, 4Department of Gastroenteralogy, Nagoya 1 IOSI, Bellinzona, Switzerland, 2, HSR, Milan, Italy, 3 Columbia Un., NY, United University Graduate School of Medicine, Nagoya, Japan States, 4 A. Avogadro Univ. of Eastern Piedmont, Novara, Italy, 5 Univ. ofModena and Reggio E., Modena, Modena, Italy, 6 CNIO, Madrid, Spain, 7 Background: Gastric MALT lymphoma is a distinct low-grade lymphoma that often Spedali Civili, Brescia, Italy, 8 Universita¨t, Basel, Switzerland, 9 Osp. Maggiore, regresses upon Helicobacter pylori eradication. The chemokine receptor CXCR3 is Milan, Italy, 10 CRO, Aviano, Italy, 11 INT, Milan, Italy, 12 Hop. Saint-Louis, Paris, a candidate molecule that could influence gastric MALT lymphoma. In this study, we France, 13 Siena University, Siena, Italy, 14 IEO, Milan, Italy, 15Varese Univ., aimed to elucidate the correlation between CXCR3 expression and the clinicopathologic features of gastric MALT lymphoma, and to determine whetherCXCR3 expression was predictive of responsiveness to H. pylori eradication.
Introduction: MZL subtypes (extranodal, EMZL; nodal, NMZL; splenic, SMZL) are Material and methods: Sixty-seven patients with gastric MALT lymphoma in a single considered unique lymphoma subtypes. Despite the fact that general clinical center study were treated with H. pylori eradication therapy. We evaluated the presentations vary and specific translocations are present only in EMZL, a high- correlation of CXCR3 expression with response to H. pylori eradication therapy by resolution genetic analysis of these disorders has not been done.
logistic regression stratified according to potential confounders.
Material and Methods: DNA from frozen biopsies analyzed with Affymetrix Human Results: Immunohistochemical analysis revealed that 28 of 67 cases (42%) were Mapping 250K arrays. Gene expression profiling with U133 plus 2.0 was performed on positive for CXCR3 expression. CXCR3 expression was significantly more prevalent in those without H. pylori infection, advanced stage disease, and in those with API2- Results: 38 out of 138 already collected samples have been analyzed so far: 10 NMZL, MALT1 fusion. In overall analysis, those with CXCR3 expression showed a significantly 10 EMZ, 18 SMZL. All subtypes had recurrent gains of chromosome 3, 12q13.3-q15, increased risk of non-responsiveness to H. pylori eradication therapy (OR = 28.6; 95% 14q32.33 and losses of 7q11.23, 19q13.2-pter, 19q13.2. Recurrent gains were CI, 5.70 to 143.4) compared to those without CXCR3 expression. This higher risk was identified in chromosome 18 (NMZL and SMZL), 1q21.3-q32.1 (EMZL), 8p23, 18q23, observed consistently regardless of sex, API2-MALT1 fusion, H. pylori infection, and 20q13.33 and 21q22.3 (SMZL). Recurrent losses were identified in 7q32.1-q32.3, 14q24.2-q32.13 (SMZL), 9q34.3, 11q13.1, 16p13.3, 16p13.11 (NMZL and EMZL), Conclusions: We showed that CXCR3 expression was an independent predictive factor 12q24.11, and 17p13.3 (NMZL). Recurrent regions of copy-neutral LOH, suggestive of for non-responsiveness to H. pylori eradication therapy in patients with gastric MALT uniparental disomy (UPD), were observed at 10q26.13 (SMZL), 2p21 (EMZL), and 6p21.32-p21.33 (NMZL). However, only 1/38 cases had UPD stretches longer than 5Mb, and this was different from what we have observed in other B-cell tumors (>150),which show UPD in as many as 50% of the cases.
Conclusions: In the first series of MZL cases analyzed, in addition to known disease-specific aberrations, novel lesions have been identified. Complete data on over 150 MICRORNA EXPRESSION IN NODAL AND EXTRANODAL C. Mandrup1, A. Petersen1, A.D. Hoejfeldt1, H.F. Thomsen1, J. Madsen1, PROGNOSTIC SIGNIFICANCE OF PRIMARY EXTRANODAL J. Dahlgaard1, P. Johansen2, A. Bukh1, K. Dybkaer1, H.E. Johnsen1 DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) IN PATIENTS 1Department of Hematology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 2Pathological Institute, Aalborg Hospital, Aarhus UniversityHospital, Aalborg, Denmark D. Hui1, B. Proctor1, J. Donaldson1, T. Shenkier1, P. Hoskins1, R. Klasa1,K. Savage1, R. Gascoyne2, J.M. Connors1, L.L. Sehn1 Introduction: The aim of this project was to analyse microRNA (miRNA) expression 1Medical Oncology, Vancouver Cancer Centre, Vancouver, BC, Canada, in nodal and extranodal diffuse large B-cell lymphoma (DLBCL). Manifestation at 2Pathology, Vancouver Cancer Centre, Vancouver, BC, Canada diagnosis may be nodal and/or extranodal. At present, there are no knowndeterminants for none of the manifestations, and no way to predict the potential Background: Previous studies in the pre-rituximab era have identified important progression from nodal to extranodal disease. miRNA are small regulatory RNA clinical differences between nodal and primary extranodal DLBCL. We have examined molecules, which function to repress/cleave sequence complementary mRNA targets.
the prognostic significance of primary extranodal DLBCL in the post-rituximab era.
Abnormalities in miRNA genetics and expression are known to affect initiation and Methods: Using the Lymphoid Cancer DATAbase of the British Columbia Cancer development of human diseases, and miRNAs are anticipated to play a direct role in Agency, all patients ‡18 years of age diagnosed with DLBCL between January 1999 and oncogenesis and differentiation. Therefore, we hypothesise miRNA to be important for May 2006 and treated with an R-CHOP regimen were included for analysis. Patients both characterization and progression of DLBCL.
were excluded if they were HIV positive, presented with disease in the testicular or Materials and Methods: A global miRNA screen (Exiqon miRCURYTM LNA Array) of central nervous system, or had known coincident indolent lymphoma. Primary 50 snap-frozen DLBCL (40 nodal, 10 extranodal), identified differentially expressed extranodal DLBCL was defined as disease confined to one or more localized extranodal miRNAs between the two manifestations. Subsets of miRNA profiles are pending to be sites, with no or minimal nearby nodal involvement.
validated by Taqman RT PCR assays in the original 50 snap frozen samples, 50 highly Results: 513 patients were identified with the following characteristics: median age 62 y selected FFPE samples and 10 new snap-frozen samples.
(range 19-93), male 59.1%, stage III/IV 53.8%, elevated LDH 49.5%, and performance Results: It was possible to distinguish between the nodal and extranodal manifestations status ‡2 38.2%. While 350 (68.2%) had at least some degree of extranodal with the global miRNA screen (e.g. mir143, mir432, mir127, and mir195).
involvement, only 133 (25.9%) had primary extranodal DLBCL. Among patients with Differentially expressed miRNA target genes were predicted by target prediction primary extranodal disease, 70 (52.6%), 37 (27.8%) and 26 (19.6%) had 1, 2 and ‡3 software (Targetscan and Miranda). Statistically software (GOstat) to annotate target extranodal sites, respectively. The most commonly involved extranodal sites included gene ontology revealed several prominent ontologies like proliferation (e.g. WNT5a, bone (33.1%), soft tissue (28.6%), stomach (15.0%), intestine (12.8%), and sinus MAPK), and cell adhesion (several members of the PCDHA family) to be differentially (10.5%). Thirty-two percent, 20%, 0% and 48% of patients with primary extranodal affected in the two manifestations. Interestingly many miRNA had the wnt pathway as DLBCL had stage I, II, III, and IV, respectively. This is in contrast to 11%, 34%, 26% and 29% for the nodal DLBCL group. Primary extranodal DLBCL was less commonly Conclusion: The two manifestations were distinct from each other with respect to associated with an elevated LDH (37.6% vs. 53.7%, p=0.001). With a median follow-up miRNA expression; this difference may provide extra information about this of 2.8 years, no significant difference in overall survival was detected between primary heterogeneously disease, and lead to further studies of the differentiated miRNAs to extranodal and nodal DLBCL analyzed either as a group or by individual stages.
examine the step wise progression from nodal to extranodal manifestation.
Furthermore, no specific primary extranodal site confers a worse prognosis.
ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org Conclusion: In the post-rituximab era, the previously identified survival difference in THE ROLE OF RADIOTHERAPY, PERFORMANCE STATUS, AND primary extranodal DLBCL is no longer observed in this large cohort.
DOSAGE OF METHOTREXATE ACCORDING TO THEAGEIN PRIMARYCNS LYMPHOMA PATIENTS RECEIVED UPFRONT HIGH DOSEMETHOTREXATE BASED CHEMOTHERAPY IPI AND FLIPI ARE NOT APPLICABLE IN PATIENTS WITH MALT J. Kim,1 W. Kim,2 C. Suh,3 D. Yang,4 H. Eom,5 S. Bang,6 S. Oh,7 S. Lee,8 H. Kim,9J. Park,10 J. Won,11 S. Yoon,12 C Kim13 and Korean Society of Hematology 1Int.Med.I, Med.University, Vienna, Austria 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul,Korea; 2Samsung Medical Center;3 Asan Medical Center; 4Chonnam National Background: The prognostic value of the international prognostic index (IPI) and the University; 5National Cancer Center; 6Seoul National University Bundang follicular lymphoma international prognostic index (FLIPI) has widely been Hospital; 7Dong-A University; 8Dankook University; 9Hallym University; 10Gil demonstrated in diffuse large B-cell lymphoma and follicular lymphoma. No attempts Medical Center; 11Soonchunhyang University; 12Seoul National University;13 to assess their applicability in MALT lymphoma have been performed so far.
Patients and Methods: 153 patients MALT-lymphoma were analysed. Parameters ofboth IPI [age>60 years, extranodal involvement ‡2, elevated LDH, PS ‡2, stage ‡3] and Introduction: We evaluated the role of RTx after CTx, initial performance status, and FLIPI [age>60 years, elevated LDH, stage ‡3, nodal involvement ‡5, hemoglobin £12g/ total cumulated dosage of MTX according to the age in PCNSL.
dl] were assessed and correlated with relapse and time to relapse as markers of clinical Material and methods: 188 immunocompetent PCNSL patients (median age 50 years) course. Statistical analysis was done with SPSS 14.0. Partial correlation was assessed receiving CTx containing high-dose MTX (>1 g/m2) were selected at 17 institutions.
with the Pearson coefficient (CF) and reassessed with multiple regression analysis.
Results: Age£50 years, ECOG<2 and RTx after CTx were significant prognostic factors Estimated time to relapse curves were calculated with the Kaplan Meier method and predicting improved OS. Multivariate analysis indicated that ECOG<2 (P=0.044, tested for significant differences with the Log-Rank test.
OR=1.76) and RTx after CTx (P=0.001, OR=2.69) were significant prognostic factors Results: According to the IPI 109 patients (71%) were classifed as low risk, 21(14%) as for prediction of OS. Planned treatment was CTx alone (group1) in 64 (34%, median low-intermediate, 16(10%) as high-intermediate, and 7(5%) as high risk. FLIPI age 61 years) patients and CTx followed by RTx (group2) in 124 (66%, median age 46 identified 100 patients (68%) at low, 33(22%) at intermediate and 14(10%) at high years). Among the patients£50, group2 patients survived longer than group1 (3-years risk. After a median follow up time of 58 months, 132 patients are alive and 60 have OS; 79% vs 56%, P=0.03). Other risk factors were not statistically significant. Adding relapsed (median time to relapse: 40 months). Neither IPI (CF:0.06, p=0.395) nor cytarabine to MTX based CTx, combination MTX based CTx, and adding intrathecal FLIPI (CF:0.06, p=0.4) correlated with relapse or time to relapse. Univariate analysis CTx did not improved OS in the PCNSL patients£50. Multivariate analysis indicated demonstrated stage, extragastric disease, autoimmune disease, trisomy 18 and that higher total cumulated dosage of MTX (‡5 g/m2) (P=0.041) was significant multifocal disease as significantly correlated with relapse, while trisomy 18, extragastric prognostic factor for prediction of OS in the PCNSL patients£50. Among the disease and multifocal disease were correlated with shorter time to relapse. Multiple patients>50, group 2 patients also survived longer than group 1 (3-years OS; 73% vs regression analysis identified only extragastric and mutifocal disease as predictive 39%, P=0.01). ECOG<2 was significant prognostic factor for prediction of OS factors of relapse (p=0.08; p=0.011). The time of follow-up was also significantly (P=0.03). Other factors including total dose of MTX were not significant.
Conclusions: In the younger PCNSL patients, CTx followed by RTx improved survival Conclusion: IPI and FLIPI are not relevant for predicting the clinical course of MALT- and sufficient total cumulated dosage of MTX or combination MTX based CTx lymphoma. Multiple regression analysis has demonstrated a significant correlation regimen might improve the OS. In elderly PCNSL patients, initial ECOG was the between follow-up time and relapse as well as extragastric MALT lymphoma and relapse and time to relapse. In view of this, prolonged follow-up is warranted inpatients with MALT lymphoma, especially of extragastric origin.
CANDIDATE GENE EXPRESSION PROFILING BY REAL-TIME PCR IN FORMALIN FIXED AND PARAFFINE EMBEDDED (FFPE)SAMPLES OF PRIMARY CNS LYMPHOMAS (PCNSL) THE NF-kB PATHWAY AS A TARGET TO INCREASE APOPTOSIS IN PRIMARY MEDIASTINAL B-CELL LYMPHOMA L. Fischer1, M. Hummel2, A. Korfel1, D. Lenze2, A. Ehlers2, P. Martus3, M. Weller4, (PMBL): STUDIES WITH SMALL MOLECULE IKK INHIBITOR ML120B, BORTEZOMIB (BTZ), CYCLOPHOSPHAMIDE (CY) AND 1Hematology, Oncology & Transfusion Medicine, Charite´ Campus Benjamin Franklin, Berlin, Germany, 2Institute of Pathology, Charite´ Campus BenjaminFranklin, Berlin, Germany, 3Institute of Biometrics and Clinical Epidemiology, I. Waxman1, C. van de Ven1, J. Ayello1, N. Day1, M.S. Cairo2 Charite´ Campus Mitte, Berlin, Germany, 4Dept. of Neurology, University Hospital 1Pediatrics, Columbia University, New York, United States, 2Pediatrics, Pathology & Medicine, Columbia University, New York, United States Background: The evaluation of biological prognostic factors in PCNSL has yielded PMBL is a rare subtype of diffuse large B-cell lymphoma (DLBCL) with a significantly contradictory results thus far. In this study we evaluated the feasibility of PCR based lower EFS than other identically treated DLBCLs (Lones/Cairo, JCO, 2000).
gene expression profiling using FFPE samples from immunocompetent PCNSL Upregulation of anti-apoptotic NF-kB pathway genes occurs in PMBL (Rosenwald, J patients. Expression of candidate genes with prognostic impact in nodal diffuse-large Exp Med, 2003). We studied the effect of 2 NF-kB pathway blocking agents, BTZ and B-cell lymphoma (DLBCL) was correlated to survival in PCNSL.
ML120B (supplied by Millennium Pharm, MA), and Cy on apoptosis in PMBL to Methods and Material: FFPE tumor samples from PCNSL patients obtained by open identify strategies to increase cell death.
resection were collected, and samples with a tumor content of >70% were subjected PMBL line Karpas-1106P was incubated with ML120B (10 lg/ml), BTZ (5 ng/ml), to RNA analysis. RNA was extracted using commercially available kits and reverse Cy (1.25 mg/ml), ML120B+BTZ or ML120B+Cy for 24h. Percentage of cells induced to transcribed with sequence specific primers. The expression of BCL2, BCL6, CCL3, undergo apoptosis was measured using Annexin V-FITC. DLBCL line SUDHL-6, with CCND2, HGAL, FN1, MYC, MUM1, LRMP, PLAU and IL4 was measured and low expression of NF-kB genes, was used for comparison. For combination studies, normalized to the mean expression of four endogenous control genes: GAPDH, GUSB, comparisons were made between single and combination therapy samples run PKG1, SDHA. Overall survival (OAS) was determined using the Kaplan-Meier method and the prognostic impact of gene expression using the Cox model.
Significant increases in PMBL apoptosis occurred after incubation with each agent Results: Samples from 42 patients with PCNSL, all histologically DLBCL, and a median (ML120B: 4.0%±1.13, p<.0005; BTZ: 5.25%±1.43, p<.02; Cy: 4.8%±1.05, p=.006).
age of 63 (26-87) years were evaluated. All patients have been initially treated with Significant increases occurred in SUDHL-6 after treatment with BTZ (46.42%±6.52, high-dose (4g/m2) methotrexate, followed by a consolidating and rescue whole brain p<.0001), but not after treatment with Cy or ML120B. ML120B+BTZ led to irradiation in 10 patients each. RNA could be extracted from all samples.
a synergistic increase in apoptosis in PMBL when compared to ML120B single agent Electrophoretic quality control identified considerable RNA degradation. Except for therapy (17-fold [1700%] increase, p<.01) and BTZ single agent therapy (4-fold IL4, the expression of all genes could be measured in 40 samples (95%). The median [400%] increase, p<.01), respectively. In contrast, ML120B+BTZ did not cause an OAS of all patients was 29 (0.5-69) months. None of the genes examined had increase in apoptosis in SUDHL-6, with no significant change in apoptosis found after a statistically significant influence on survival, however, a trend towards longer survival treatment with ML120B+BTZ vs. BTZ alone (BTZ: 25.92%±1.32, ML120B+BTZ: was seen for the overexpression of FN1 (HR 1.35, p=0.09), and PLAU (HR 1.27, 24.62%±5.19, difference in increase between BTZ & BTZ+ML120B: 1.29%, p=NS).
p=0.17), and the reduced expression of CCND2 (HR 0.87, p=0.19). Patients <60 years ML120B+Cy in PMBL led to an additive increase in apoptosis (ML120B: 5.49%±1.74, had a median OAS of 32 months compared to 24 months for older patients (p=0.3).
Cy: 6.57%±1.16, ML120B+Cy: 13.82%±2.3, p<.03).
Karnofsky index had no impact on survival.
ML120B and BTZ both increase apoptosis in PMBL, possibly by blocking the NF-kB Conclusion: FFPE material is suitable for RT-PCR based analysis of genes with possible pathway at different points. This may explain why combination therapy with prognostic impact in PCNSL. However, the results obtained yielded no statistical ML120B+BTZ is synergistic, while the effect of ML120B+Cy is additive. Studies to significance. This might be due to their inability to predict clinical outcome in PCNSL assess expression of NF-kB genes in PMBL after single and combination therapy are or to the relatively small cohort investigated.
ADDITION OF RITUXIMAB TO CHOP GREATLY IMPROVES THE 1Department of Internal Medicine, Seoul National University Hospital, Cancer OUTCOME OF PATIENTS WITH PRIMARY MEDIASTINAL LARGE Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of, 2Department of Ophthalmology, Seoul National University Hospital,Seoul National University College of Medicine, Seoul, Korea, Republic of, T. P. Vassilakopoulos1, G. Pangalis1, Z. Galani1, S. Sachanas1, A. Katsigiannis2, 3Department of Pathology, Seoul National University Hospital, Seoul National E. Vrakidou3, C. Poziopoulos4, N. Constantinou5, P. Repoussis6, M. Dimopoulou1, University College of Medicine, Seoul, Korea, Republic of S. Kokoris1, E. Michali1, E. Dimitriadou1, S. Masouridis1, M. Siakantaris1,C. Kalpadakis1, M. Kyrtsonis1, P. Panayiotidis1, P. Poussou2, M. Angelopoulou1 Introduction: Despite a variable association between ocular adnexal MALT lymphoma 1Dept of Hematology, University of Athens, Laikon University Hospital, Athens, and Chlamydia psittaci (Cp) infection, high rate of Cp-positivity was observed in Greece, 23rd Dept of Internal Medicine, University of Athens, Athens, Greece, Korean patients with ocular adnexal MALT lymphoma. Additionally, there are 3Hematology Dpt, Hygeia Hospital, Athens, Greece, 4Hematology Dpt, General conflicting results regarding Cp-eradicating doxycycline. This study was undertaken to Army Hospital, Athens, Greece, 5Hematology Dpt, Theageneion Hospital, analyze the efficacy of blind doxycycline in localized ocular adnexal MALT lymphoma.
Salonica, Greece, 6Hematology Dpt, METAXA Hospital, Athens, Greece Materials and methods: Twenty-one patients diagnosed as extranodal marginal zoneB-cell lymphoma of MALT type were analyzed. Doxycycline at a dose of 200mg daily Background: Rituximab-CHOP (RCHOP) is superior to CHOP, being the new for 3 weeks was given to unselected patients with ocular adnexal MALT lymphoma as standard of care for patients with diffuse LBCL. In PMLBCL, which usually affects a first-line (n=17) or second-line (n=4) between 2005 and 2007. Lymphoma response young patients, several investigators prefer the use of MACOP-B or even front-line and progression-free survival (PFS) were analyzed.
high dose therapy with autologous stem cell support (HDT-ASCT). However, the role Results: Patients’ median age was 47 with a male-to-female ratio of 0.6:1. Doxycycline of RCHOP in PMLBCL is not well established yet.
was well-tolerated in ocular adnexal lymphoma patients, of whom only one Patients and Methods: 82 patients with PMLBCL were treated in 6 centers (1994- discontinued doxycycline after one week due to dizziness. Seven patients (33%) 2007): 39 consecutive patients who received RCHOP±Radiotherapy (RT) were achieved lymphoma regression (2 complete responses and 5 minimal responses), while compared to 43 consecutive historical controls, who had received CHOP±RT.
remaining 14 patients showed stable disease. In the first-line group, two-year PFS rate Results: The median age of the patients was 31 years (17-82) and 53/82 (65%) were was 65% and median PFS was 22.2 months. In patients with disease progression, females. All individual IPI parameters and B-symptoms were balanced between the two subsequent chemotherapy or radiotherapy induced complete response in 4 out of 6 groups. The median follow-up of currently alive patients was 33 and 88 months for patients. However, in the second-line group, two-year PFS rate was 50% and median patients treated with RCHOP±RT and CHOP±RT respectively. All failures occurred PFS was 10.5 months. Overall, 13 (62%) of 21 patients remained progression-free after within 22 months from diagnosis. The 3-year failure free survival (FFS) was 81±6% vs doxycycline therapy after a median follow-up of 18 months.
53±8% for patients who received RCHOP±RTvsCHOP±RT (p=0.006). The 3-year Conclusions: Doxycycline alone is effective in localized ocular adnexal MALT event free survival (EFS) was 79±7% vs 51±8% (p=0.007). The 3-year overall survival lymphoma as a first-line treatment. Future efforts should be directed toward was 92±5% vs 67±7% (p=0.009), while the 3-year lymphoma specific survival (LSS) determining the Cp status and finding a marker associated with doxycycline resistance.
Conclusions: RCHOP±RT provided very good results in PMLBCL: Early progressions CHLAMYDOPHILA PSITTACI (CP) IS VIABLE AND INFECTIOUS were minimized, long-term FFS exceeded 80%, and only 3 lymphoma-related deaths IN THE CONJUNCTIVA AND PERIPHERAL BLOOD OF PATIENTS were recorded so far in 39 patients after a median follow-up of 33 months. Patients WITH OCULAR ADNEXAL MALT LYMPHOMA (OAML): RESULTS OF A treated with RCHOP had significantly higher FFS, EFS, OS, and LSS, when compared to CHOP-treated historical controls. Based on these results we continue to treatPMLBCL patients with RCHOP±RT, avoiding more intensive strategies.
A.J. Ferreri1, R. Dolcetti2, G.P. Dognini3, L. Malabarba3, N. Vicari4, E. Pasini2, NO BENEFIT OF ADDING RITUXIMAB TO CHOP REGIMEN IN M. Ponzoni3, M. Cangi3, L. Pecciarini3, A. Giordano Resti3, C. Doglioni3, PATIENTS WITH PRIMARY EXTRANODAL TYPE OF DIFFUSE LARGE Dept. of Oncology, San Raffaele H Scientific Institute, Milan, Italy, 2 Centro di Riferimento Oncologico, Aviano, Italy, 3 San Raffaele H Scientific Institute, Milan, G. Jang1, S. Kim1, D. Lee1, S. Kim1, H. Kim2, C. Suh1 Italy, 4 National Reference Laboratory for Animal Chlamydioses, IZSLER, Pavia, 1Internal medicine, Asan Medical Center/University of Ulsan college of medicine, Seoul, Korea, Republic of, 2Internal medicine, Hallym University Medical Center,Anyang, Korea, Republic of Background: Some lymphomas are linked to specific bacterial infections.
Confirmation of these associations by bacteria isolation from patients’ (pts) samples Background: The addition of rituximab to CHOP chemotherapy (R-CHOP) has (second Koch’s postulate) has been achieved for H. pylori, but not for other lymphoma- significantly improved clinical outcome for patients (pts) with diffuse large B-cell related bacteria. OAML is linked to Cpinfection, but the viability and infectivity of this lymphoma (DLBCL). However, new predictors of response to R-CHOP have not been microorganism in OAML pts has not been investigated yet.
established. We performed a retrospective analysis to evaluate the clinical impact of Methods: A single-center prospective trial was conducted to assess the prevalence of Cp R-CHOP and tried to identify clinical predictors to get better benefit from R-CHOP infection in 20 OAML pts and 42 healthy blood donors referred to our Institution in compared with CHOP in pts with DLBCL.
a 6-month period, and to define whether the Cp DNA and antigens previously detected Material and methods: Using the population-based cancer registry for non-Hodgkin’s in OAML pts correspond to a viable and infectious microorganism. The presence of Cp lymphoma of Asan Medical Center, we identified eligible 177 pts who were newly on conjunctival swabs and peripheral blood mononuclear cells (PBMC) of pts and diagnosed with CD20-positive DLBCL and treated with CHOP (n=82) or R-CHOP donors was assessed by TETR-PCR and in vitro cultural methods. The presence of Cp (n=95) as first-line therapy from January 2001 to November 2005. We especially was assessed also in lymphoma tissue.
subgrouped all pts into either primary extranodal lymphoma (PENL, n=72) or nodal Results: Donors were more commonly young males living in urban areas, whereas lymphoma (NL, n=105) according to the main origin of disease. PENL was defined as OAML pts frequently reported a history of chronic conjunctivitis and prolonged lymphoma which had either no or minor nodal involvement along with a clinically contact with household animals (85% vs. 38% of donors; p=0.00001). Cp was detected dominant extranodal component after routine staging procedures. Response rate, in lymphoma tissue of 15 (75%) pts. Cp DNA was detected in conjunctival swabs and/ event-free survival (EFS) and overall survival (OS) were compared between CHOP and or PBMC from 10 (50%) OAML patients and in PBMC from one (2%) donor R-CHOP group. To identify clinical predictors, subgroup analysis was performed with (p=0.01). Viability and infectivity of Cp, demonstrated by growth in cell cultures, were log-rank test and Cox regression model.
confirmed in conjunctival swabs and/or PBMC from 5 (25%) OAML pts, but not in Results: Complete response rate and overall response rate were higher in R-CHOP than CHOP group though it didn’t meet statistical significance between two groups Conclusions: This prospective trial demonstrates, for the first time, that Cp is viable (79% vs 69%, p=0.16 and 97% vs 90%, p=0.07). Two-year EFS and OS rates were and infectious in conjunctival swabs and/or PBMC of OAML pts. Cp infection is higher in R-CHOP group (82% vs 74%, p=0.22 and 83% vs 77%, p=0.23). In subgroup common in OAML pts and exceptional in blood donors. Epidemiological features in analysis, pts with NL had a prominent survival benefit from R-CHOP over CHOP OAML pts are consistent with increased risk of Cp exposure.
(p=0.02 in EFS and p=0.03 in OS) but pts with PENL did not (p=0.37 in EFS andp=0.61 in OS). Other factors such as age, ECOG performance status, stage, LDH and VALUE OF 18F-FDG-PET SCAN IN THE DIAGNOSIS AND IPI showed no difference for survival outcome according to treatment regimen.
STAGING OF OCULAR ADNEXAL LYMPHOMA (OAL): A LARGE Conclusions: R-CHOP regimen showed improved outcome in pts with DLBCL compared with CHOP, but pts with PENL had no benefit from addition of rituximabto CHOP chemotherapy. These pts might need other treatment strategy.
M. Zanni1, G. Moulin-Romsee2, V. Servois3, P. Validire1, C. Plancher4,L. Lumbroso-Le Rouic5, R. Dendale6, A. Vincent-Salomon7, M. Be´namor2,B. Asselain4, L. Desjardins8, C. Precupanu1, C. Le´vy8, D. Decaudin1 ANTI-TUMOR ACTIVITY OF BLIND DOXYCYCLINE IN 1Clinical Hematology, Institut Curie, Paris, France, 2Nuclear Medicine, Institut LOCALIZED OCULAR ADNEXAL MUCOSA-ASSOCIATED LYMPHOID Curie, Paris, France, 3Radiology, Institut Curie, Paris, France, 4Biostatistics, Institut Curie, Paris, France, 5Ophthalmology, Institut Curie, Paris, France,6Radiotherapy, Institut Curie, Paris, France, 7Tumor Biology, Institut Curie, Paris, K. Kim1, T. Kim1, S. Lee1, D. Kim1, S. Khwarg2, C. Kim3, D. Heo1 France, 8Ophthalmology, Institut Curie, Paris, France Introduction: Fluorine 18 deoxyglucose Positron Emission Tomography (PET) is CGH/FISH and data from expression profiling of microdissected lymphoma cells of largely used in the staging of non-Hodgkin’s lymphomas (NHL), but very few studies a cDNA chip containing 2300 genes. Feature class selection for isolation of new have focused on its role in the initial staging of patients (pts) presenting ocular adnexal prognostic genes was performed. TP53 protein and proliferation index were evaluated lymphoma (OAL). The aim of this study was therefore to evaluate the role of FDG-PET in the diagnosis of ophthalmologic lymphomatous localizations.
Results: In 7/22 lymphomas a deletion (5/22) or a mutation (5/22) of TP53 was Patients and Methods: A retrospective review of all imaging records, including detected. When compared to the numbers of genomic aberrations no correlation computed tomography (CT), magnetic resonance imaging (MRI), and 18F-FDG-PET regarding a higher number of aberrations was detected. More than two cytogenetic of all OAL pts treated at the Institut Curie between 2003 and 2007 was performed. The aberrations were correlated with significantly shorter mean survival, while TP53 failed ability of PET studies to detect lymphomatous ophthalmologic involvement was then as a predictor. Genomic profiling of deleted and mutated TP53 lymphomas revealed compared with other staging explorations.
four differentially expressed genes in both groups (false discovery rates 0.003 and 0.006, Results: Thirty-one OAL pts were included in the study. Pathological review according respectively). These were PTPRD, which is an analogue of CD45; CCNG2, a cell cycle to the WHO classification showed 22 low-grade lymphoma pts (71%) in whom 15 regulator; MAPK12, a major transducer of extracellular signals; and CCL7, a monocyte MALT lymphoma (48%) and 9 high-grade NHL in whom 6 diffuse large B-cell chemotactic protein. Nuclear TP53 protein accumulation was generally low in the lymphoma (19%). Ophthalmologic sites were intra-orbital in 20 pts (65%) in whom 3 deleted cases while TP53 was heterogeneously detected in the mutated lymphomas with bilateral localizations and conjunctival in 14 pts (45%) in whom 3 with bilateral ranging from 5% to 95% positive lymphoma cells.
localizations. All patients had FDG PET and orbital MRI assessment at diagnosis in 21 Conclusions: A core group of four differentially expressed genes was defined that cases and orbital CT in 28 pts. 18F-FDG PET positive lesions were correlated to might be influenced by mutations/deletions of TP53. Furthermore, feature selection for pathological sites detected by MRI in 12/21 pts (57%) and 6 pts had negative FDG PET class selection of complete remission revealed a group of differentially expressed genes but positive MRI;18F-FDG PET positivity was correlated to pathological sites detected by CT in 17/28 pts (61%). At last, concordances between PET/MRI and PET/CT were71% (p=0.06) and 79% (p=0.02), respectively. The sensitivity of FDG PET, MRI, andCT were 77%, 87%, and 80%, respectively.
CLINICOPATHOLOGICAL FEATURES AND OUTCOME OF Conclusions: As anticipated, this study shows that 18F-FDG-PET has a lower sensitivity STAGE I GASTRIC MALT LYMPHOMA TREATED WITH than MRI to detect ophthalmologic lymphomatous localizations.
G. Pinotti1, A. Stathis2, C. Capella1, I. Proserpio1, C. Chini1, F. Bertoni2, PROGNOSTIC VALUE EXPRESSION OF CD38 IN PRIMARY 1Oncology and Pathology, Ospedale di Circolo and University of Insubria,Varese, Italy, 2IOSI, Oncology Institute of Southern Switzerland, Bellinzona, N. Kondratieva1, I. Poddubnaya1, E. Sholohova1, E. Osmanov1, O. Moskalenko1, Switzerland, 3ICP, Institute of Pathology, Locarno, Switzerland N. Tupitsyn11Chemotherapy of Haemoblastosis, Cancer Research Center after N.N. Blokhin, Background: The efficacy of Helicobacter Pylori (HP) eradication in localized gastric MALT lymphoma is well established with remission rates between 60-100% of cases.
However, only scanty information is available about long-term follow-up of antibiotic- Background: B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) represent a clinically, morphologically and biologically heterogeneous group. There is Methods: 100 patients (pts) with stage I gastric MALT lymphoma were treated initially no information about prognostic value expression of CD38 in MALT-lymphomas. The with anti-HP eradication regimens comprising antibiotics in association with proton- aim of our study was to evaluate the level of expression CD38 and outcome of patients pump inhibitors. Follow-up endoscopies with multiple biopses were carried out at 6 with primary gastric MALT-lymphomas.
Materials: We have studied immunohistological features of 34 pts with primary gastric Results: Median age at diagnosis was 64 years. All patients presented with MALT-lymphomas stage I (Lugano) treated between 1995-2005. There were 15 (44%) gastrointestinal symptoms (mainly abdominal pain/dyspepsia) but no B symptoms males and 19 (56%) females. Age of patients (pts) ranged 21-79 years (median 58). The were observed. HP was detected by histology in 80%. Lymphoma was most often median of follow-up was 36 months (range 3-96). Two groups were identified. First localized in the antrum (30%), was multifocal in 19%, associated with gastritis in 54% group (3 pts) - expression of CD38 on lymphoma cells, second group (31 pts) and with ulcers in 29% of cases. After antibiotics, HP was eradicated in all positive - expression of CD38 on plasmocytes. Last group may be subdivided in two groups: 12 patients (19 of them after a second line of antibiotics). Symptoms disappeared and (39%) pts with low level of CD38+ plasma cells (group A) and 19 (61%) pts with macroscopic findings improved in almost all patients. Lymphoma regression was intensive CD38+ plasma cell reaction (group B). Helicobacter pylori infection status achieved in 78 of 97 evaluable patients (80%, 95% CI.: 71-88%) with histological was assessed as positive in 31 cases. Antibacterial treatment was performed for 31 complete remission (CR) in 66 (Wotherspoon’s score 0-2) and partial remission patients with expression of CD38 on plasmacytes. Three patients with expression of (score 3) in 12 pts. A multifocal presentation was significantly (p=0.04) associated with CD38 on lymphoma cells were treated by chemotherapy.
lower CR rate (47%) in comparison with fundus+ body (65%) and antrum (82%). The Results: Results were analysed in group A and B. Complete remission was observed in median follow-up time was 6.5 years; 34 of the 78 responders showed continuous 93%. Eight (27%) pts had relapses: 6 relapses were mainly in group B, only 2 in group histological remission, while 33 had histological score fluctuations (from 0-4) and A. The 2-years disease free survival was 86% in pts with low level of CD38+ plasma cell, 11 pts had a frank lymphoma relapse (2 with high-grade trasformation). The 5-year 53% in pts with intensive CD38+ plasma cell reaction (not significant).
and 10-year overall survivall rates were 91% (95% CI, 83-95) and 82% (95% CI, 69-90), Conclusions: The present results show that the cases of primary gastric MALT- lymphomas stage I (Lugano) with different level of CD38+ plasma cell in lymphoma Conclusions: Hp eradication therapy resulted in CR in the majority of cases, with tissue have various clinical outcome, long-term survival and risk for relapses. These a significantly higher CR rate in tumors of the distal stomach. Long-term clinical results could be taken into account for the individual treatment for patients with disease control was achieved in most cases. Incidence of histologic transformation primary gastric MALT-lymphomas with initial high CD38+ plasma cell proportion.
seems lower in gastric MALT lymphoma than in other low-grade lymphomas.
Future studies of expression CD38 may be helpful for assessment of prognosis forpatients with gastric MALT-lymphomas.
INTRAVASCULAR LARGE B-CELL LYMPHOMA (IVLBCL): INTERNATIONAL CONSENSUS ON DIAGNOSTIC AND THERAPEUTIC INSTABILITITY AND EXPRESSION PROFILES IN 22 DIFFUSE LARGEB CELL LYMPHOMAS OF THE GASTROINTESTINAL (GI)-TRACT M. Ponzoni1, A.J. Ferreri1, E. Campo1, G.P. Dognini1, F. Facchetti1, T. Kinoshita1,L. Mazzucchelli1, T. Yoshino1, T. Murase1, M. Seto1, K. Shimada1, S.A. Pileri1, T.F. Barth1, T. Zenz2, H.A. Kestler3, M. Buchholz4, T. Gress5, S. Stilgenbauer6, C. Doglioni1, E. Zucca1, F. Cavalli1, S. Nakamura1 1Pathology, San Raffaele Scientific Institute, Milano, Italy, On Behalf of 1Institute of Pathology, University of Ulm, Ulm, Germany, 2University of Ulm, International Intravascular Lymphoma Study Group Internal Medicine III, Ulm, Germany, 3Neural Information Processing, Universityof Ulm, Ulm, Germany, 4Gastroenterology, Philipps University, Marburg, Background: IVLBCL is a rare form of diffuse large B-cell lymphoma with preferential Marburg, Germany, 5Gastroenterology, Philipps University, Marburg, Marburg, intravascular growth of malignant lymphocytes, aggressive behavior, and usually fatal Germany, 6Internal Medicine III, University of Ulm, Ulm, Germany course. IVLBCL often affects elderly patients with poor PS, elevated LDH serum levels,anemia, and B-symptoms, with possible differences in clinical presentation between Introduction: TP53 is regarded as one of the main tumor suppressors. Deletion and/or cases diagnosed in Western Countries and Japan. Many characteristics of IVLBCL are mutations of TP53 are believed to cause genomic instability and neoplastic poorly known and may be broader than those currently described.
Methods: On behalf of the International Extranodal Lymphoma Study Group, Material and methods: Twenty-two diffuse large B cell lymphomas of the GI-tract clinicians and pathologists interested in IVLBCL, coming from Western and Eastern were analyzed for deletion and mutations of the TP53 by FISH and sequencing. The countries, joined to reach a consensus on the most urgent unresolved issues in IVLBCL: data were correlated with a database that integrated genomic abberrations detected by to this end, a representative group of IVLBCL cases coming from Western countries and Japan were collectively analyzed. IVLBCL features were proposed both under Objective and Patients: To evaluate the usefulness of rituximab in IVL, we clinical and pathologic standpoints.
retrospectively analyzed 106 patients (59 men, 47 women) with IVL who received Results: the consensus indicated that: IVLBCL have additional morphological criteria chemotherapy either with rituximab (R-chemo, n=49) or without rituximab (Chemo, including definition of affected vessels, cell size (somewhat smaller cell may occur), n=57) between 1994 and 2007 in Japan. Median patient age was 67 years (range, 34 to peculiar sites of involvement (kidney, spleen and liver), and immunophenotype (in 84 years). IPI was H-I/H in 97% of patients.
particular CD5 expression); difference in clinical forms of IVLBCL is driven more by Results: Complete response rate was higher for R-chemo (82%) than for Chemo (51%, the presence of haemophagocytosis rather than geographical origin of patients; P=0.001). Median duration of follow-up for surviving patients was 18 months (range, 1 ‘‘cutaneous variant’’, PS, stage, and therapeutic modality are independent prognostic to 95 months). Progression-free survival (PFS) and overall survival (OS) rates at 2 years variables; therapy is improved by anthracycline-based chemotherapy plus rituximab, after diagnosis were significantly higher for R-chemo (PFS: 56%; OS: 66%) than for CNS prophylaxis and consolidation with high-dose chemotherapy supported by Chemo (PFS: 27%, P=0.001; OS: 46%, P=0.01). Multivariate analysis revealed use of autologous stem cell transplant, mostly in high-risk and young patients.
rituximab was favorably associated with PFS (HR, 0.45; 95% CI, 0.25 to 0.80; P=0.006) Conclusion: IVLBCL is a peculiar type of diffuse large B-cell lymphoma under and OS (HR, 0.42; 95% CI, 0.21 to 0.85; P=0.016). Adverse events related to rituximab pathological, immunophenotypic, clinical and therapeutical standpoints. An infusion were observed in 14 of 49 patients (29%). Grade 3 hypoxia due to rituximab international prospective protocol, aimed to study both therapeutical and biological infusion was observed in one of 49 patients (2%). Treatment-related death was features of this disease is currently being designed.
observed in 3 patients (6%) with R-chemo and 5 patients (9%) with Chemo. Twelve of For more information, please contact: ponzoni.maurilio@hsr.it, 49 patients (24%) in the R-chemo group and 31 of 57 patients (54%) in the Chemo group had died as of final follow-up. In the R-chemo group, 4 patients each died ofprogressive disease (PD) and relapsed disease (RD), respectively. In the Chemo group,15 patients and 11 patients died of PD and RD, respectively.
Conclusion: Our data suggest improved clinical outcomes for patients with IVL in the rituximab era without significant increase in toxicities. Future prospective studies of PATIENTS WITH INTRAVASCULAR LARGE B-CELL LYMPHOMA (IVL) rituximab-containing chemotherapies are warranted.
G.P. Dognini1, M. Ponzoni2, O. Bairey3, C. Montalba`n4, A. Szomor5, L. Uziel6,J. Seymour7, A. Ambrosetti8, M. Martelli9, G. Rossi10, M. Federico11,A. Candoni12, A. De Renzo13, M. Piris14, E. Zucca15, C. Doglioni2, A.J. Ferreri1 PRIMARY TONSIL NON-HODGKIN’S LYMPHOMA, CLINICAL 1Dept. of Oncology, San Raffaele H Scientific Institute, Milan, Italy, 2Pathology CHARACTERISTICS, PROGNOSIS AND SURVIVAL ANALYSIS Unit, San Raffaele H Scientific Institute, Milan, Italy, 3Div. of Hematology, RabinMedical Center, Beilinson Hospital, Petah Tiqwa, Israel, 4Servicio de Medicina Interna, Hospital Ramo´n y Cajal, Madrid, Spain, 5First Dept. Medicine, Univ. of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Pecs, Pecs, Hungary, 6Hematology Unit, Ospedale San Paolo, Milan, Italy, Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China 7Australasian Leukaemia and Lymphoma Group, and Univ. of Melbourne,Melbourne, Australia, 8Hematology Unit, Policlinico G.B. Rossi, Verona, Italy, Objectives: This study aimed to analysis the clinical characteristics, prognostic factors 9Div. of Hematology, Universita` La Sapienza, Rome, Italy, 10Hematology Unit, and treatment outcome of Chinese patients with primary non-Hodgkin’s lymphoma Spedali Civili, Brescia, Italy, 11Hematology Unit, H Policlinico, Modena, Italy, 12Hematology Unit, Policlinico Universitario, Udine, Italy, 13Div. of Hematology, Methods: From May 1990 to March 2007, 106 patients with previously untreated NHL Universita` Federico II, Naples, Italy, 14Div. of Pathology, Centro Nacional de of tonsil were retrospectively reviewed. The median age was 49 years. In theall 106 Investigaciones Oncolo`gicas, Madrid, Spain, 15Div. of Medical Oncology, Ist.
patients, 68.9% diagnosed of diffuse large-B-cell lymphoma (DLBCL), 11.3% of Oncologico Svizzera Italiana, Bellinzona, Switzerland peripheral-T-cell lymphoma (PTCL) and 7.5% of indolent B-cell lymphoma. Ninety-eight (92.5%) patients presented with stage I and II disease. Majority of patients Background: The addition of rituximab to anthracycline-containing chemotherapy (69.8%) received combined chemoradiotherapy and 17.9% treated by radiotherapy has significantly improved outcome in patients (pts) with diffuse large B-cell alone as initial treatment. The predominant chemotherapy regimens were CHOP and lymphomas. The impact of this monoclonal antibody in IVL, a rare variant of diffuse BACOP, and radiotherapy dose range between 40-50Gy.
large B-cell lymphoma characterised by the growth of neoplastic cells into small blood Results: After a median follow-up of 51 months, the estimate 5-year overall survival vessels was recently explored in a large series of Japanese pts, while experience in IVL (OS) and disease free survival (DFS) were 82% and 68%, respectively. Significant pts diagnosed in Western Countries is limited to a few case reports prognostic factors included: advanced disease and locally extra-nodal involvement.
Methods: The impact of the addition of rituximab was evaluated in 28 pts affected by Other prognostic factors, such as age older than 60 years, B symptoms, bulky disease, CD20+ IVL eligible for CHOP/CHOP-like regimen: 8 pts were treated with rituximab T cell lymphoma and treatment modalities as chemoradiotherapy or radiotherapy +chemotherapy (R-CT) and 20 with chemotherapy alone (CT).
alone did not show significant results on outcome.
Results: Median age was 67 yrs (range 39-86; 15 males). 75% of pts had an IPI‡3.
Conclusions: Survival for the patients with primary tonsil NHL is optimal as most of B symptoms, PS‡3, increased LDH levels, and stage IV were respectively observed in the patients have stage I or II diseases. Diffuse large-B-cell lymphoma is the most 78%, 41%, 88%, and 71% of cases. Skin (44%), CNS (30%) and bone marrow (30%) common pathological subtype. Multivariate analysis by Cox regression shows that were the most common sites. Laboratory tests revealed: anemia (78%), leucopenia advanced stage, primary refractory disease and locally extra-nodal infiltration are (30%), thrombocytopenia (37%), and increased LDH (88%). No significant differences between R-CT and CT groups were observed. Overall, 18 (64%) pts Keywards: tonsil neoplasms; Non-Hodgkin’s lymphoma; chemotherapy; achieved complete remission (CR), and 2 partial response with an early progression (PD), 6 (21%) experienced a PD, and 2, both in CT group, died of toxicity. NoteworthyCR was obtained in 100% of R-CT versus 50% of CT pts (p=0.03); the addition ofrituximab was related to CRR. At a median f-up of 14 mo, all 8 R-CT pts are alive and DIFFUSE LARGE B-CELL LYMPHOMAS OF THE WALDEYER’S relapse free; at a median f-up of 71 mo, only 7 CT pts are alive and disease-free. The RING: A CLINICO-PATHOLOGICAL STUDY OF 209 PATIENTS FROM 3-yr EFS was 35% in CT group and 100% for R-CT pts (p<0.0001); the 3-yr OS was THE GROUPE D’ETUDE DES LYMPHOMES DE L’ADULTE (GELA) 39% and 100%, respectively (p<0.0001).
Conclusions: the addition of rituximab to anthracycline-based chemotherapy Laurence de Leval1,5, C. Bonnet2,5, C. Copie-Bergman4,5, L. Seidel3, M. Baia4, significantly improves outcome in IVL pts diagnosed in Western Countries. A J. Brie`re4, T. Molina5, B. Fabiani5, B. Falini5, C. Gisselbrecht5, H. Thilly5, A. Albert3, confirmatory international prospective trials is warranted.
On behalf of the International Extranodal Lymphoma Study Group (IELSG) Departments of Pathology1 Hematology2, Biostatistics3, CHU Sart-Tilman,Lie`ge, Belgium; Department of Pathology, Hoˆpital Henri Mondor4, Cre´teil,France; GELA group5 A RETROSPECTIVE ANALYSIS OF RITUXIMAB-CONTAINING CHEMOTHERAPIES FOR INTRAVASCULAR LARGE B-CELL DLBCLs are markedly heterogeneous, and their biological features may vary according to the primary site of disease. The WR is the second most common site of extranodalinvolvement by DLBCL.
K. Matsue1, K. Shimada1, K. Yamamoto1, T. Murase1, N. Ichikawa1, We analyzed 209 adult patients with de novo DLBCL presenting in the WR M. Okamoto1, N. Niitsu1, H. Kosugi1, N. Tsukamoto1, H. Miwa1, H. Asaoku1, consecutively included in the GELA trials (1993-2004) (M/F: 1,8; mean age 59 yrs; 81% A. Kikuchi1, M. Matsumoto1, Y. Saburi1, Y. Masaki1, M. Kashimura1, T. Yoshida1, stages I-II) and treated with anthracyclin-based polychemotherapy. Morphology and M. Yamaguchi1, S. Nakamura1, T. Naoe1, T. Kinoshita1 immunophenotype were analyzed and correlated to the clinical features. FISH assays 1Intravascular Large B-cell Lymphoma Study Group, IVLSG, Nagoya, Japan with split-signal DNA probes were performed on a subset of cases. Survival andoutcome were compared to a matched cohort primary nodal DLBCL patients.
Background: Intravascular large B-cell lymphoma (IVL) is a rare subtype of extranodal By morphology, 55% of WR DLBCLs were centroblastic, 39% centroblastic- diffuse large B-cell lymphoma (DLBCL) with poor prognosis. Addition of rituximab to polymorphous, 3% immunoblastic, and 3% unclassifiable. Among large biopsy CHOP and CHOP-like regimens has been found to improve the outcome of DLBCL.
specimens (n=79), 53% had a prominent or minor nodular pattern and 47% were However, the efficacy of rituximab in IVL remains unclear.
purely diffuse. The prevalence of antigen expression was: bcl2: 105/189 (60%); CD10: 75/178 (42%); bcl6: 40/76 (53%); mum-1:40/109 (37%). The immunophenotype modalities used so far. MTh also appears to be important for consolidation or even of 136 cases was GC-like in 60% and non-GC-like in 40%. In multivariate analysis, GC-like cases correlated with better OS (p=0.014). Rearrangement of BCL-2, BCL6 andc-MYC loci were found by FISH in 3/42, 9/35 and 3/41 cases. For 144 paired WR/nodal cases, the CR rate was significantly better for WR patients (p=0.01) but the 5-yOS and EFS rates (79,7% and 70,9% in WR patients, and 76,7% and 66,7% in nodalpatients) did not significantly differ. For 109 paired patients with no adverse prognosticfactor of the aa IPI, primary WR localization was associated with a higher 5-y EFS ACTIVITY OF BORTEZOMIB IN MALT LYMPHOMAS: A IELSG (78,5% vs. 71,2%; p=0,029) and 0S (84,7% vs. 79,8%; p=0,047) rates.
In conclusion, WR DLBCLs frequently have a partially follicular pattern of growth, and a GC-like phenotype. In DLBCL patients with an aa IPI = 0, the WR localization A. Conconi1, A. Lopez-Guillermo2, G. Martinelli3, L. Rigacci4, U. Vitolo5, appears to confer a better outcome than primary nodal involvement.
P.L. Zinzani6, A. Ferreri7, S. Luminari8, M. Martelli9, F. Cavalli10, E. Zucca101Hematology, ASO Maggiore della Carita`, Universita` Amedeo Avogadro,Novara, Italy, 2Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, RITUXIMAB MONOTHERAPY IS THE TREATMENT OF CHOICE Barcelona, Spain, 3Hematology, European Institute of Oncology, Milan, Italy,4 Hematology, Careggi Hospital and University of Florence, Florence, Italy, 5Hematology, ASO San Giovanni Battista, Turin, Italy, 6Institute of Oncology and C. Kalpadakis1, G.A. Pangalis2, T.P. Vassilakopoulos2, M.N. Dimopoulou2, Hematology L. and A. Sera`gnoli, University of Bologna, Bologna, Italy, 7Onco- M. Kyrtsonis2, P. Korkolopoulou2, F. Kontopidou2, M. Siakantaris2, hematology, San Raffaele Institute, Milan, Italy, 8Oncology and Hematology, E. Dimitriadou2, P. Panayiotidis2, H. Papadaki1, M. Angelopoulou2 University of Modena and Reggio Emilia, Modena, Italy, 9Hematology, University 1Dept of Hematology, University of Crete, University Hospital of Heraklion, of Rome, Rome, Italy, 10Oncology Institute of Southern Switzerland, IOSI, Heraklion, Heraklion, Greece, 2Dept of Hematology, University of Athens, Laikon The International Extranodal Lymphoma Study Group (IELSG) is coordinating Introduction: There is no standard therapy for SMZL. Splenectomy has been a phase II trial aimed to assess the antitumor activity and safety of bortezomib in considered as the first line treatment although it may carry significant complications.
patients (pts) with relapsed or refractory extranodal marginal zone B-cell lymphoma of We present our results on the efficacy of Rituximab as a first line treatment in SMZL MALT-type. Bortezomib 1.3 mg/m2 is administered on days 1, 4, 8, and 11 of a 21-day cycle, for up to 6 cycles. Response and progression are determined by InternationalWorkshop Criteria. As of January 2008, 25 pts have been enrolled in the study: among Patients and methods: We analysed 24 pts with SMZL diagnosed in our Dpt between the 21 pts in whom the data are available, 12 (57%) patients were male, median age was 2003 and 2007. All pts received Rituximab at a dose of 375mg/m2/week for 6 63 years (range, 38–81). At time of enrolment, the Ann Arbor stages distribution was consecutive weeks at a median time of 1,5 mo after diagnosis. Maintenance therapy the following: stage I=5 pts (24%), stage II=5 pts (24%), stage IV=11 (52%). In 11 pts (MTh) was given as one dose of 375mg/m2 Rituximab every 2 mos for one year. Pts’ primary gastric localization was present, in 5 cases primary skin, in 2 cases primary median age was 57 years (range 48-78). At diagnosis all pts had splenomegaly and bone subcutaneous, moreover a primary lung, orbit, muscle localization was reported in 1 pt marrow infiltration. Response criteria were defined as follows: CR: complete clinical, each. All patients had ECOG PS=0; in 3 cases (14%) elevated serum LDH was reported.
morphologic and immunophenotypic remission, unconfirmed CR: clinical and More than 1 site of extranodal localization was present in 5 pts (24%). Median number laboratory CR without bone marrow evaluation, PR: 50% improvement of clinical and of prior therapies was 2 (range, 1–3). Median follow-up was 17 months. Eleven pts were assessed for response at the end of treatment plan: 3 pts had a CR (27%); 4 a PR (37%) Results: Overall response was 100%. All pts had complete resolution of splenomegaly and 3 SD (27%) and 1 a PD (9%). Four additional pts, with ongoing therapies, have at a median time of 5 weeks (median 2-15) after treatment initiation along with been evaluated after the first two courses of therapy: one pt achieved a CR, 1 pt a PR, restoration to normal of their blood counts at a median time of 4 weeks (1-44). 17 pts 1 pt a SD and in 1 a PD was observed. Significant duration of response was observed (71%) achieved a CR, 4 an unconfirmed CR (17%), and 3 (12%) a PR. Among the CR’s among the 4 pts in CR, ranging from 18 to 22 months and in most cases still ongoing.
5 pts had also a molecular remission. 20 pts underwent MTh, while 4 did not. 12/20 pts The safety profile of bortezomib is similar to that observed in multiple myeloma and have already completed MTh. 10/12 pts who completed MTh sustained their response other subtypes of non-Hodgkin lymphoma. The most relevant grade 3 or higher and 2 pts achieved an improvement of response. 2 relapses were recorded at a median adverse events were peripheral neuropathy and fatigue. Three deaths, non-related to time of 21,5 mos. Median follow up time for the entire series is 29 mos (range 6-91). No treatment, were observed during the early follow up. These preliminary results suggest that bortezomib is active and safe in relapsed or refractory MALT lymphomas and Conclusions: The present study demonstrates that Rituximab is a highly effective encourage us to complete the studies accrual.
treatment for SMZL. It confers better response rates in relation to other treatment Disclosure: Research Funding: Johnson & Johnson partially supported the trial.

Source: http://www.lymphcon.ch/imcl/doc/ICML_AbstractBooks_vecchi/10-ICMLJune4-72008/58_PosterII_186-91.pdf

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