ALBERT

Beschreibung: Abstract 582 Chromosomal translocations (t) are usually analyzed as one group, and are associated with poor prognosis in chronic lymphocytic leukemia (CLL). Translocations involving immunoglobulin (IG) genes are recurrent, but uncommon (〈 5%) in CLL. The two most frequent IG-partners are BCL2 (18q21) and BCL3 (19q13). On the behalf of the Groupe Francophone de Cytogenetique Hematologique (GFCH), we report an extensive analysis of 75 t(14;18)-CLLs, and a comparison to our previously published series of 29 t(14;19)-CLLs (Chapiro et al, Leukemia 2008). The 75 t(14;18)-CLLs or variant BCL2-t have been collected between 1985 and 2009. The morphological and immunological reviews were performed by KM, CS, and HM-B. All karyotypes were reviewed by the GFCH. Fluorescence in situ hybridization analyses were performed to detect IG and BCL2 rearrangements, trisomy 12, and deletions of 11q22 (ATM), 17p13 (TP53), 6q21, 13q14 (D13S319). IGHV mutation analyses were performed by referring laboratories. Statistical analyses were carried out using the Fisher's exact test, and continuous data using the Mann-Whitney test. Overall survival (OS) and treatment free survival (TFS) calculated from diagnosis were estimated using the Kaplan-Meier method, and the statistic significance was determined using log-rank test. Among BCL2-CLL, the sex ratio was 57M/18F, the median age at diagnosis was 66 years; of 68 patients with available data, 63 (93%) presented with Binet stage A; median lymphocytosis was 14.6×109/l. There were 47/75 (63%) “classical” CLL and 28/75 (37%) “atypical” CLL, with more than 10% of lymphoplasmacytoid cells and/or large cells. All tested cases (58/58) were CD10-, 69/73 (94%) were CD5+, and 44/63 (70%) were CD38-; 57/68 (84%) had a Matutes score 〉 4, 7/68 (10%) a score = 3, 4/68 (6%) a score 〈 3. We observed 62 t(14;18) and 13 variant translocations [11 t(18;22), 2 t(2;18)]. The karyotype was complex (〉 3 abnormalities) in 15/74 (20%) cases, and the BCL2-t was isolated in 25/74 (34%) cases. There were 33/75 (44%) tri12, 32/68 (47%) del13q14, 1/72 (1%) delTP53, 0/72 (0%) delATM, 0/59 (0%) del6q21. Of 42 analyzed cases, 33 (78%) were mutated. Finally, the median time from diagnosis to first therapy was 24 months (m). Comparisons with the BCL3-CLL showed no difference in sex ratio, age, and Binet stages. The lymphocytosis was lower in BCL2-CLL (14.6 vs 24.4 x109/l, p

Beschreibung: Introduction HCV infection is associated with the development of B-cell non Hodgkin lymphomas (NHL), preferentially of marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL) subtypes. Other subtypes of B-cell NHL are rare. HCV-related lymphomagenesis may constitute in some cases a model of lymphoma induced by chronic antigenic stimulation. Moreover, a direct role of an infection of B cells by HCV is also an alternative hypothesis. We performed a multicentric observational study of HCV-related B-cell NHL in France in order to study the real distribution of their histological subtypes and their correlation with in situ expression of HCV virus. Patients & Methods Adult patients with B-NHL and active HCV infection were included in an observational multicentric study with the exclusion of those who were co-infected with HIV. Data were collected from patients with either ongoing or past history of HCV infection. Cytological and histological samples were collected for centralized review and molecular analyses. A large panel of antibodies was performed on each sample for subtyping the B-cell NHL and HCV-NS3 antibody immunostaining was made each time we had enough material. Results Between 2006 and 2012, 133 consecutive patients were enrolled in 26 French hospitals, among them 17 patients were excluded from analysis. At lymphoma diagnosis the median age was 61 years and the gender M/F ratio was 1. Histological samples of 81/116 patients were reviewed by a panel of expert hematopathologists. The most frequent B-cell NHL subtype was DLBCL in 30/81 patients (37.5%) among them 14/30 (46.6%) were transformed from underlying low grade B-cell NHL. For 26/30 DLBCL we had enough material for performing Hans score: 18 (69%) were of non germinal center (GC) origin and 8 (31%) of GC origin. Interestingly, most de novo DLBCL were of non GC subtype (92%) whereas in transformed DLBCL 50% were of non GC subtype. MZL represent 22/81 cases (27%), 8/81 (9.9%) were follicular lymphomas and other small B-NHL subtypes represent the other cases. Patients with DLBCL displayed frequent extra-nodal involvement (digestive tract, liver) (60%) and those with MZL had the highest proportion (73%) of extranodal localisations (spleen, bone marrow, blood, eye) whereas follicular lymphomas were mainly developed in lymph nodes. Twenty-nine cases could be tested for HCV NS3 antibody, 26 exhibited evaluable staining: 12 B-NHL had in situ positive staining (most of them were DLBCL (67%) with a slight predominance of transformed DLBCL compared to de novo (62%) and 14 had negative staining (most of them were MZL or other small B-cell NHL (92%). Conclusion This study underlines the heterogeneity of HCV-related B-cell NHL with a majority of extra-nodal localizations of these lymphomas, a predominance of DLBCL and MZL and a high proportion of DLBCL developed on low grade B-NHL comparing to de novo DLBCL. We found a different GC/non GC repartition between de novo versus transformed DLBCL with a higher proportion of GC versus non GC in transformed DLBCL than in de novo DLBCL. In situ HCV virus expression was more frequently observed in DLBCL than in other subtypes of B-NHL which could indicate that the growth and development of lymphoma cells may be associated with the presence of HCV infection of B cells. Therefore, we postulate that the B cell transformation is linked with chronic antigenic stimulation in MZL and to direct infection in DLBCL. It might also explain that virological success seems to improve prognosis preferentially in MZL subtype in our series. Disclosures: Haioun: Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Beschreibung: Abstract 3116 Background: Hepatitis C virus (HCV) associated B-cell non-Hodgkin's lymphoma (B-NHL) is a rare entity that constitutes a model of chronic immune stimulation related lymphomas. They are preferentially Marginal Zone Lymphomas (MZL) and Diffuse Large B Cell Lymphoma (DLBCL) subtypes. In order to study the characteristics of HCV-related B-NHL, we pursue a prospective multicentric observational study in France. We present here the characteristics and evolution of the patients included in this study. Patients and methods: Adult patients with a history of HCV associated B-NHL were included in the study. HCV infection was defined by a positive viral load at diagnosis of NHL. Patients with HIV infection were excluded from the study. Each patient was followed every 6 months during 5 years. Data collection included clinical presentation, treatment and evolution of NHL and HCV infection. Pathological and cytological materials were centralized and reviewed by a group of expert hematopathologists, haematologists and immunologists. Results: The data of the 64 consecutive patients included between nov 2006 and march 2010 in 20 centers are presented. Median age is 62 years (ranging from 39 to 87 years). There is a predominance of men: sex ratio 1.37 (m37/f27). HCV genotypic distribution does not differ from expected in France: 1: 52% (30/56), 2: 25% (14), 3: 11% (6), 4: 12% (7), 7 missing data. Twenty-six cases were included at diagnosis of B-NHL, 33 during follow-up of NHL and 5 at relapse. The median interval between NHL diagnosis and last follow-up is 22 months (range 0–152). The histological subtype distribution is DLBCL 39% (22), MZL 37% (21), FL 16% (9), CLL 4% (2), mantle cell lymphoma 4% (2). Remarkably, there is a continuum between MZL and DLBCL, with 6 cases with ongoing transformation. Eight cases are not classified due to small disease infiltration or lack of material. Expert review led to reclassification in few cases from DLBCL to MZL and from FL to MZL. Among the 22 patients with DLBCL, 3 have no follow-up. The median follow-up of the remaining 19 patients is 21 months. Those patients were treated with polychemotherapy combined with rituximab (R) in all cases except one. Treatment was followed by long lasting complete remission (CR) in all cases except three: a 59 y woman relapsed after Richter syndrome following CLL, a 85 y man progressed on therapy and a 40 y woman with liver DLBCL was resistant to 3 lines of R-chemotherapy. These three patients died from disease progression. During follow-up, 9 patients were treated with antiviral treatment followed by virologic response in all cases but one. The 21 patients with MZL are 8 splenic MZL including one with transformed DLBCL, 7 nodal MZL, 3 extra-nodal, and 3 Waldenstrom macroglobulinemia; 15 out of 19 cases were associated with positive rheumatoid factor (RF) and/or cryoglobulinemia. Two patients had no follow-up. The median follow-up of the remaining 19 patients is 40 months. The efficacy of antiviral treatment alone on HCV-associated MZL was confirmed in 8 patients and had a RF. The other patients were treated with R-chemotherapy (4), R+antiviral (2), R (2), oral chemotherapy (1) or “watch and wait” (1). The patient with splenic high grade transformation was treated by splenectomy alone and is still in CR. During follow-up, one patient relapsed and is currently treated with R-chemotherapy, two patients died including one after progression to DLBCL. Among the 9 patients with FL, one had no follow-up, 6 long-lasting CR were obtained following R-chemotherapy, one following three lines of treatment. One other CR was obtained following R-antiviral therapy. Three other patients received antiviral therapy during follow-up with efficacy in one case. Among the two patients with mantle cell lymphoma, one had no follow-up, the other one is on long term CR 6 years following first line chemotherapy (R-CHOP/R-DHAP). Conclusions: This study strengthens the heterogeneity of HCV-related lymphomas and the need for systematic expert review. Overall, these patients have a favourable outcome. Cases with MZL frequently respond to antiviral treatment and one case with FL to R-antiviral. Combined therapy of R- antiviral seems a good option and should be evaluated for low grade lymphomas. Patients with DLBCL should receive R-CHOP therapy and should be referred in hepatology department for antiviral treatment after chemotherapy due to frequent virologic responses and follow up of liver functions. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Deletions of the long arm of chromosome 14 are rare (