ALBERT

Description: Abstract 2667 Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by bone marrow infiltration by lymphoplasmacytic lymphoma associated with a monoclonal component of IgM type in the serum. WM is often preceded by an IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). The cumulative probability of progression of IgM-MGUS to WM or to other lymphoproliferative disorders is approximately 1.5% per year. Other mature B-cell neoplasms such as splenic marginal zone lymphoma (SMZL) and B-cell chronic lymphoproliferative disorders (B-CLPD) can carry an IgM monoclonal component and should therefore be considered in differential diagnosis with WM. In a study based on parallel sequencing of the whole genome of lymphoplasmacytic cells and paired normal tissue from WM patients, Treon et al (Blood. 2011;118:Abstract 300) have identified a highly recurrent somatic mutation with oncogenic activity in the myeloid differentiation primary response (MYD88) gene, leading to a change from leucine to proline at position 265 of the aminoacid sequence [MYD88 (L265P)]. Targeted Sanger resequencing showed MYD88 (L265P) in 90% of WM patients, but only in a minority of patients with IgM-MGUS or other mature B-cell neoplasms such as SMZL. We developed an allele-specific PCR for the MYD88 (L265P) mutation, and studied 58 patients with WM, 77 with IgM-MGUS, 84 with splenic marginal zone lymphoma (SMZL) and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). DNA was obtained from bone marrow cells (n=204) and peripheral blood (n=67). The aims of this study were: i) to assess the prevalence of the mutation in WM, IgM-MGUS, SMZL, and B-CLPD; ii) to analyze the relationship between MYD88 (L265P) mutation and clinical phenotype; iii) to evaluate the impact of the mutation on the risk of progression from IgM-MGUS WM or other lymphoproliferative disorders. The MYD88 (L265P) mutation was detected in 58/58 (100%) patients with WM, either asymptomatic (n=39) or symptomatic (n=18), and in 36/77 (47%) patients with IgM-MGUS. In addition, it was detected in 5/84 (6%) patients with SMZL and in 3/52 (6%) with B-CLPD; of these MYD88 (L265P)-positive subjects, 4 SMZL and 2 B-CLPD patients carried a serum IgM monoclonal component, while the remaining B-CLPD patient carried a double (IgM and IgG) monoclonal component. Compared with IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) had significantly higher levels of IgM (P

Description: Abstract 2876 Background: HCV infection has been demonstrated to be involved in clonal B cell proliferation and in the subsequent development of non-Hodgkin's lymphoma (NHL). The regression of NHL after antiviral treatment is considered an indirect evidence of this pathogenetic relationship. Aim: to evaluate clinical course of patients affected by HCV infection (serology and HCV RNA positive) and low grade B-cell NHL (LG-NHL), not needing immediate treatment (absence of B symptoms, bulky disease or symptomatic tumor mass and lymphocyte doubling time less than 6 months) and treated upfront with antiviral therapy alone. Method: From 2006 to 2010, 13 patients, affected by LG- NHL at diagnosis have been treated with pegylated interferon (PegIFNa2a, 100–180 mcg weekly) and ribavirin (Rbv, 800–1200 mg daily) for a median treatment period of 6 months (6-18 months). Two patients are still in treatment. M/F ratio was 1.6 and median age was 59 years (range 51–73). The study included 9 marginal zone lymphomas (MZL: 2 splenic MZL, 7 extranodal non gastric MZL), 3 LG-NHL NOS and 1 lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL). Cryoglobulin were present in five patients. 7 pts had genotype 2, 5 pts genotype 1b, one not assessed; HCV infection was detected before lymphoma diagnosis in 9 pts and at lymphoma onset in 4 pts. Only 2 patients have previously received other combinations of antiviral therapy. Virologic response was assessed monthly by HCV-RNA polymerase chain reaction (PCR) and hematologic response was evaluated according to International Working Group response criteria (Cheson et al. J Clin Oncol. 2007) at the end of antiviral therapy. Results: Eleven patients completed the planned treatment course. Sustained virologic response (SVR) was achieved in 9 patients (6 with genotype 2); viremia clearance was achieved in a median period of 2 months (1-6). Among patients that gained a SVR, 5 achieved a complete response (CR) (3 genotype 2, 1 1b, one not assessed), one (genotype 2) partial response (PR), and 3 (2 genotype 2 and one genotype 1b) presented stable disease (SD). The remaining patients obtained only a reduction of viremia: one presented a SD and one was in PR. The treatment was well tolerated without any WHO grade III-IV toxicity. Among patients that completed treatment program, more frequent toxicity was haematological (one patient developed a WHO grade 1 anemia and one patients developed WHO grade 1 anemia and grade 2 neutropenia). After a median follow up of 17 months from the end of therapy (range 3–44), considering the 9 patients in SVR, only 2 (1 CR and 1 PR) progressed, maintaining SVR and one lost SVR maintaining SD. Patients that obtained only a reduction of viremia, maintained their hematologic status. Conclusion: We described a high CR rate in patients that obtained SVR after antiviral therapy (55%); the relationship between hematologic and viral response during follow up is not always stringent. We confirm that antiviral therapy could be considered as frontline therapeutic option in cases of HCV-related LG-NHL not requiring immediately immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1585 Splenic marginal zone lymphoma (SMZL) is frequently associated with HCV infection and autoimmune disorders. Previous studies demonstrated a biased usage of immunoglobulin heavy variable genes (IGHV) and, in some cases, stereotyped B-cell receptors (BCRs). This characterization, however, is mainly based on the heavy chain alone, even if strong evidences are emerging on the role of light chain (Bikos et al. Leukemia 2012). The aim of this study was to analyze IG light variable genes (IGLV) of SMZL BCRs, VL-VH pairing and structural information and to investigate the sequence-structure-antigen (AG) relationship. To this end, we analyzed the VL-VH paired sequences of BCR from 52 SMZL pts (38 BM and 14 PB) diagnosed according to Matutes criteria (Leukemia, 2008). Sequences were analyzed using the IMGT/DBs and the IMGT/V-QUEST tool. The PIGS web server was used to build 3-D models of all antibodies (Abs). The Ab structures were compared using LGA and clustered together according to a score accounting for structure and sequence similarity. Using the DIGIT DB and tools, all the clusters were analyzed and compared to other IGs. Based on the IGHV nucleotide sequence identity to the germline, 7 sequences (13%) were considered ‘truly unmutated’ (100% sequence identity), 20 (39%) were ‘minimally or borderline mutated’ (97–99.9%) whereas 25 (48%) were ‘significantly mutated’ (3%), whereas samples using the IGHV1-02 gene (n=10) but a VL gene other than from IGLV1-47 displayed a low number of mutations, suggesting a significant role for the light chain. In order to analyze the possible functional role of light chain, we analyzed the structural similarity of AG binding sites (ABSs), performing hierarchical clustering on the similarity obtained by an all-against-all structural superposition of each ABS. Twenty structural clusters were identified (8 with ≥3 samples) (Fig. 1). Considering IGs in the same major groups, they showed a similar mutation rate, pointing out a likely common AG selection at least in a fraction of pts (Fig. 1). In most cases, IGs in the same clusters display ABSs with similar physicochemical characteristics: positively charged binding sites (2 clusters), hydrophobic patches (3 clusters) or small pockets in the middle of the ABS (3 clusters) might be clue for different AGs specific for each cluster. HCV infection was found in 1 major and 2 minor clusters (Fig. 1), mainly associated with unmutated clones, indicating a likely common antigenic stimulation. In the other major clusters, the role for an AG-driven selection different from HCV in SMZL lymphomagenesis can be postulated. In particular, 3 clusters, containing both mutated and unmutated samples, displayed a statistically significant similarity to CLL clones (p

Description: Abstract 262 Hairy cell leukemia (HCL) is an indolent neoplasm of small mature B-lymphoid cells, which are found in peripheral blood and bone marrow (BM), and are characterized by hairy projections of their abundant cytoplasm. In clinical practice, HCL needs to be differentiated from similar indolent lymphoid neoplasms. In a study based on massively parallel sequencing of the whole exome of leukemic and matched normal cells from a HCL patient and subsequent targeted resequencing in additional patients, Tiacci et al (N Engl J Med. 2011 Jun 16;364:2305–15) have recently identified the BRAF V600E mutation as a genetic alteration associated with this disease. This somatic mutation was previously detected in diverse human cancers, with a particularly high frequency in melanoma (Nature. 2002 Jun 27;417:949–54; N Engl J Med. 2005 Nov 17;353:2135–47). In order to develop a reliable molecular diagnostic tool and verify its sensitivity and specificity in the diagnosis of HCL, we developed an allele-specific PCR for the BRAF V600E mutation, and searched for this molecular lesion in a series of 239 patients with mature B-cell lymphoid neoplasms. The study population included 62 patients with HCL, 91 with splenic marginal zone lymphoma (SMZL), 29 with Waldenström macroglobulinemia (WM), and 57 with B-cell chronic lymphoproliferative disorders (B-CLPD). Genomic DNA was extracted from bone marrow (BM) biopsies in 61 cases of HCL, from BM in 90 patients with diverse lymphoid neoplasms (33 SMZL, 29 WM, 28 B-CLPD), and from peripheral blood (PB) in the remaining 88 patients (1 HCL, 58 SMZL, 29 B-CLPD). The BRAF V600E mutation was detected in all patients with HCL (62/62) and in none of those with SMZL or WM. Two of the 57 patients with B-CLPD carried the mutation, and their clinical features are as follows. Case #1. This 41 year-old woman presented in November 2008 with asymptomatic lymphocytosis, without any evidence of lymphadenopathy, splenomegaly or hepatomegaly. Laboratory data showed: Hb 12.9 g/dL, WBC count 16 × 109/L (62% lymphoid cells), and PLT count 283 × 109/L. On BM biopsy, an interstitial lymphoid infiltrate (60% of the whole cellularity) composed by small, lymphocyte/centrocyte-like cells was found. By immunohistochemistry, neoplastic cells showed expression of CD20, CD79a and cyclin-D1, but were uniformly negative for CD5, CD10, CD23, CD25 and DBA44, and annexin A1. At flow cytometry analysis, they were CD20 and FMC7 positive and CD10, CD38, CD5, CD23, CD11c, CD25, DBA44 and CD103 negative. FISH for t(11;14), performed for cyclin D1 expression, was negative. Immunoglobulin rearrangement was IGHV3-48*02, IGHD7-27*01 IGHJ4*02. So far, lymphocytosis has remained stable and the patient is regularly followed without any need for treatment. Case #2. This 62 year-old male presented in 2006 with thrombocytopenia and splenomegaly, and was diagnosed with HCL was established in another hospital (no additional data are available). He was treated with cladribine with a partial response. In May 2008, we evaluated this patient in Pavia. The spleen was palpable 3 cm under the costal margin, and laboratory data showed: Hb 15.4 g/dL, WBC count 3.9 × 109/L, and PLT vount 95 × 109/L. BM biopsy showed a 20% lymphoid infiltrate with interstitial and sinusoidal pattern, composed by small to medium sized cells with evident nucleoli, resembling pro-lymphocytes. By immunohistochemistry, cells were positive for CD20 and negative for CD5, CD23, cyclin-D1, CD25, DBA44, and annexin A1. Flow cytometry demonstrated the expression of CD20, FMC7 and CD11c, partial expression (25%) of CD103, and negativity for CD5, CD10, CD38, CD23, DBA44, CD11c and CD25. This patient was asymptomatic and a watch-and wait-policy was adopted. These findings indicate that the allele-specific PCR we developed is able to detect the mutation in the bone marrow of all patients with HCL, and confirm that the BRAF V600E mutation is highly specific for HCL within mature B-cell neoplasms. Only 2/177 (1.1%) patients with lymphoid neoplasms other than HCL (2/57 or 3.5% of patients with B-CLPD) were positive for BRAF V600E. This is in agreement with a previous study that found BRAF mutations in 2.4% of patients with non-Hodgkin's lymphoma (Br J Cancer. 2003 Nov 17;89:1958–60). The detection of the BRAF V600E mutation in the clone (or, at least, in a subclone) of mature B-cell lymphoid neoplasms without typical HCL features might help to define their biology. Disclosures: No relevant conflicts of interest to declare.

Description: The somatically acquired V600E mutation of the BRAF gene has been recently described as a molecular marker of hairy cell leukemia (HCL). We developed an allele-specific PCR for this mutation and studied 62 patients with HCL, 1 with HCL variant, 91 with splenic marginal zone lymphoma, 29 with Waldenström macroglobulinemia, and 57 with B-cell chronic lymphoproliferative disorders. The BRAF V600E mutation was detected in all HCL cases and in only 2 of the remaining 178 patients. These 2 subjects had B-cell chronic lymphoproliferative disorders that did not fulfill the diagnostic criteria for HCL. Despite the positive PCR finding, the mutation could not be detected by Sanger sequencing in these 2 cases, suggesting that it was associated with a small subclone. We conclude that the BRAF V600E mutation is present in all patients with HCL and that, in combination with clinical and morphologic features, represents a reliable molecular marker for this condition.

Description: Abstract 2821 Epidemiological studies demonstrated that HCV is associated with B-cell NHL. A precise prognostication of HCV+ NHL is not available; in particular, the impact of liver toxicity on the outcome of pts treated with (immuno)-chemotherapy is not fully clarified. Aim of the present study was to analyse clinical and virological characteristics, toxicity and prognosis of a large series of indolent and aggressive HCV+ NHL. We studied 1,043 pts with HCV+ NHL diagnosed and treated from January 1993 to December 2009 in 15 italian hematologic institutions; 539 cases were aggressive NHL (522 DLBCL) and 504 indolent NHL (265 MZL). All pts were HIV negative, 3% carried HBsAg and 91% were HCV-RNA+. Thirteen out of 56 HCV-RNA negative pts cleared HCV by means of antiviral therapy before NHL diagnosis. An (immuno)-chemotherapy regimen was administered as first-line treatment in 859 pts: 537 received CHOP-like regimen (+ Rituximab 243), 66 III generation regimen, 174 alkylators, 30 purine analogues, 31 other regimens, 21 R alone. Doses of chemotherapy since first cycle were reduced in 31% of pts. A watch-and-wait policy was adopted in 82 pts, other treatments in 68 pts and anti-HCV antiviral therapy in 34 pts with indolent NHL (12 of whom obtained both a complete virologic and hematologic response). Hepatic toxicity was evaluable in 597 patients: among 347 pts with normal ALT at NHL diagnosis, 52 (15%) developed WHO hepatic toxicity ≥ grade 2; among 250 pts (42%) with abnormal ALT, 26 (11%) experienced ALT increase 〉3.5 times baseline value. Overall, a significant liver toxicity developed in 78 pts (13%) (15% of aggressive NHL and 10% of indolent NHL). Use of Rituximab was not associated with significant liver toxicity (p=0.4); particularly, in DLBCL, R-CHOP and CHOP showed the same rate of significant hepatic toxicity (15%, p=ns), although maximum grade of liver toxicity was registered earlier in patients treated with R-CHOP than in those treated with CHOP (before 3rd cycle respectively in 57% vs 41%, p=0.006). Planned treatment was not completed in 134 pts (29 for liver toxicity). After a median F-UP of 2.6 years, 321 pts died (24 for liver failure). 5-yrs OS was 76% for indolent NHL and 62% for DLBCL. In indolent NHL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p

Description: Abstract 3495 WM is a rare malignant B-cell disorder characterized by lymphoplasmacytic infiltration of the bone marrow (BM) and hypersecretion of monoclonal IgM. IgMMGUS is an asymptomatic condition characterized by the presence of a serum monoclonal IgM protein and bone marrow infiltration 〈 10%. WM (symptomatic and indolent) and IgMMGUS can be identified based on two main features, the bone marrow infiltration and the existence of signs and symptoms. The biological and genetic characteristics of both conditions need to be explored. Our study aims to highlight the different expression profiles between WM and IgMMGUS comparing CD19+ as well as CD138+ cells. We have investigated patients with WM (n =21) and patients affected by IgMMGUS (n=10). BM CD19+ and BM CD138+ cells were isolated from 21 WM patients, while BM CD19+ and BM CD138+ were isolated from 10 and 4 IgMMGUS patients, respectively. Microarray analysis was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Data was preprocessed using Robust Multi-Array Average (RMA) software. Differential expression analysis was performed using Significant Analysis of Microarrays (SAM). Genes showing a q value lower than 5% and an absolute fold change greater than 2 were selected for further clustering analysis which was performed applying complete linkage hierarchical agglomerative clustering on Euclidean pairwise distances between genes. Microarray of WM vs IgMMGUS CD19+ cells has highlighted 151 differently expressed genes (Fig. 1). Among them we have found 33 genes involved in the regulation of transcription which were significantly overexpressed in WM vs. IgMMGUS. BM WM CD19+ cells overexpressed the following 14 Zinc Finger Protein (ZNF) genes: ZBTB40, ZNF83, ZNF137P, ZNF177, ZNF224, ZNF264, ZNF320, ZNF395, ZNF514, ZNF532, ZNF623, ZNF767, ZNF785, ZNF850. Other genes acting as regulators of transcription overexpressed in WM B cells were: HIF1AN, BHLHE41, EZH1, CCNL2, TCFL5, BLZF1, CIITA, PER2, MECP2, PRDM2, and ELP2. In particular, HIF1AN belongs to the PI3K/Akt/mTOR pathway, ELP2 is involved in the JAK/STAT process, and BHLHE41 and PER2 are included in the cicardian clock showing that these different biological mechanisms differently develop in WM with respect to IgMMGUS. TNFRSF10A, MAP4K4, TNFRSF10B, WNK1, DUSP22, ITPKB genes were overexpressed in WM B cells showing the involvement of Akt and MAPK signaling pathways which can play an important role in WM cells as they regulate several biological processes including cell growth, differentiation, survival, migration and metabolism. Gene expression profiling across CD138+ cells have demonstrated 43 differently expressed genes between WM vs. IgMMGUS (Fig. 2). MS4A1, BANK1 genes were overexpressed with high fold changes (FC) of 11.6 and 9.4, respectively, as well as GPR183, SWAP70 which were significantly overexpressed in WM vs. IGMMGUS, both genes showing a FC of 5. These results suggest that B cell activation and immune response are biological processes which act differently in WM compared to IgMMGUS. RALGPS2(FC=4), PLEKHG1 (FC=10) and ARHGAP24 (FC=4) genes mediating GTPase regulator activity of signal transduction were overexpressed in WM. ARHGAP24 could also be involved in the modulation of angiogenesis. FCRL2 and FCRLA genes involved in cell-cell signaling and cell differentiation, were significantly overexpressed in WM vs. IgMMGUS CD138+ with a fold change of 4.6 and 9, respectively. Again, the immune response seems to be a biological mechanism involved in WM CD138+ cells as CD79B (FC=5) and HLA-DOA (FC=4) genes were overexpressed in WM in respect to IgMMGUS. These differences may reflect varied immune mechanisms in the two disorders. In conclusion, the regulation of transcription, PI3K/Akt/mTOR and MAPK signaling pathways are the most relevant gene ontology biological processes occurring in CD19+ cells, while immune response, cell activation and signaling processes developing in CD138+ cells mainly distinguish WM and IgMMGUS. Future studies of the biological role of the genes differently expressed in WM vs IgMMGUS could clarify the pathogenetic processes underlying IgMMGUS and WM. The understanding of the molecular mechanisms leading to the progression of IgMMGUS to WM could help the identification of IgMMGUS patients who are at high risk for progression to WM. Fig. 1 GEP of BM WM CD19+ cells vs. IgMMGUS CD19+ cells. Fig. 1. GEP of BM WM CD19+ cells vs. IgMMGUS CD19+ cells. Fig. 2 GEP of BM WM CD138+ cells vs. IgMMGUS CD138+ cells. Fig. 2. GEP of BM WM CD138+ cells vs. IgMMGUS CD138+ cells. Disclosures: No relevant conflicts of interest to declare.

Description: Key Points Using a sensitive method, the MYD88 (L265P) mutation is detectable in all patients with Waldenström’s macroglobulinemia, therefore representing a hallmark of the disease. MYD88 (L265P) is also found in a substantial proportion of patients with IgM-MGUS.

Description: Abstract 3680 In B-cell malignancies, biased usage of immunoglobulin heavy chain variable (IGHV) genes and stereotyped clusters of immunoglobulin receptor suggest that a limited set of antigens or superantigens are involved in malignant transformation. In the present study we analyzed the IGH rearrangements of a large series of patients with Waldenström Macroglobulinemia (WM), IgM-monoclonal gammopathies of undetermined significance (IgM-MGUS) and IgM-related disorders (IgM-RD), with the aim to characterize IGH repertoire and to search for clusters of stereotyped receptors. A total of 123 patients with IgM monoclonal gammopathies, including 59 WM, 55 IgM-MGUS and 9 IgM-RD underwent IGHV amplification and direct sequencing. The median age of patients was 63 years (range: 32–86). Diagnosis of WM, IgM-MGUS and IgM-RD was made according to the consensus criteria proposed at the 2nd International Workshop on WM. All IGHV-D-J rearrangements were analyzed using the IMGT databases and the IMGT/V-QUEST tool to identify HCDR3 aminoacid (AA) sequences. HCDR3 sequences were aligned with each other and compared to 28,400 HCDR3 sequences from public databases (EMBL, NCBI, IMGT/LIGM-DB) and from unpublished multi-laboratory databases. Alignments were performed using the multiple sequence alignment software ClustalX (2.0). Criteria for including sequences in a cluster were: 〉60% aminoacid identity, IGHV gene belonging to the same clan, identical HCDR3 length and same junction residues and/or same IGHD-J genes. A productive monoclonal IGHV-D-J rearrangement was obtained in 99/123 patients, including 55 WM, 37 IgM-MGUS and 7 IgM-RD. IGHV genes were mutated in 94/99 patients (95%). The median somatic hypermutation rate was 93.3% (range 85.5%-97.9%). Four cases showed 〉98% identity with the germline sequences, whereas one single WM sample showed 100% identity with the germline sequence. When compared with the normal mature B-cell repertoire, a significant over-representation of the IGHV3 family and a significant under-representation of the IGHV1 and IGHV4 families were observed both in WM (87%, 7% and 2% respectively) and in IgM-MGUS (78%, 8% and 8% respectively). IGHV3-23 was the gene most commonly used (29%). Analysis of IGHV3-23 sequences for AA changes in the positions involved in superantigen recognition by IGHV3 subgroup genes showed that the majority of cases had two or more non-permissive AA changes that compromise the capacity to mediate superantigen recognition and binding. The frequency of novel N-glycosylation sites, introduced by the somatic hypermutation process, in this series of patients (12%) was not statistically different from that observed in normal memory B-cells, suggesting that WM, IgM-MGUS and IgM-RD cells do not need to interact with stromal GC environmental elements. The median HCDR3 length was 13 AA (range: 5–29) and was similar in WM, IgM-MGUS and IgM-RD. Intra-WM/IgM-MGUS/IgM-RD search for HCDR3 similarity showed no association that met minimal requirements to define stereotyped receptors. The comparison of WM/IgM-MGUS/IgM-RD sequences with non WM/IgM-MGUS/IgM-RD database showed that WM/IgM-MGUS/IgM-RD sequences are unrelated to known CLL or SMZL subsets. Only one IgM-MGUS occurring in a HCV-positive patient formed a novel subset with other 4 HCV-related lymphoproliferative disorders. The findings of this analysis of WM, IgM-MGUS and IgM-RD IGH sequences indicate that: i) family-usage in the WM, IgM-MGUS and IgM-RD showed a skewed usage compared to normal B-cell repertoire; ii) WM, IgM-MGUS and IgM-RD-specific HCDR3 clusters do not occur to a frequency detectable with currently available databases; iii) WM, IgM-MGUS and IgM-RD sequences are not related to known CLL and SMZL HCDR3 clusters; iv) one IgM-MGUS showed similarities with sequences derived from pathological HCV-related lymphoproliferations, suggesting that, at least in a fraction of cases, HCV may have a pathogenetic role. For the large majority of IgM-related disorders, however, there is little evidence in favor of a B-cell receptor-driven pathogenesis. Disclosures: No relevant conflicts of interest to declare.

Description: Background Indolent non follicular B-Cell Lymphomas (INFL) are a heterogeneous group of lymphomas and include small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphomas (LPL), and marginal zone lymphomas (MZL). In 2010 the NF10 study was proposed by the Fondazione Italiana Linfomi as a prospective registry specifically devised for investigating the prognosis of this group of lymphomas with particular emphasis on splenic MZL. Methods The purpose of the study is to verify whether a prospective collection would provide more accurate data to better define prognosis of INFL. The registration of consecutive patients with newly diagnosed INFL satisfying entry criteria is ongoing at a dedicated website via secure HTTP protocols. Each patient should be followed for up to 5 years. So far the study has been activated in several centers in Europe, South America and Asia. Patients who have a locally established diagnosis of SLL, LPL, or MZL and have never received anti-lymphoma therapy are eligible for inclusion in the study. All ages and disease stages were allowed. Results Between September 1st 2011 and August 1st 2013, 215 cases from 28 European and South American Institutions have been registered. At time of current analysis, data on 186 cases were available. Based on local pathology report 12% of cases were registered as SLL, 19% as LPL and 57% as MZL, including splenic (20%), nodal (15%), and extranodal (22%) subtypes; 12% of cases were classified has CD5-negative B-cell chronic lymphoproliferative disorders. Median age was 66 years (rage 28-90), 54% of patients were males; Ann Arbor stage was I-II in 23% and III-IV in 77%; 13% had B symptoms, 10% had ECOG performance status 〉 1, LDH and Beta2-microglobulin were elevated in 19%, and 49% of cases, respectively. Six percent of cases were HCV positive. Regarding HBV infection, 20% of patients were HBcAb-positive and only 3% of patients were HbsAg-positive. Among baseline characteristics, also details on initial treatment plan were collected; an immediate systemic therapy was planned in 48% of cases and included the use of anti-CD20 monoclonal antibody in 94% of cases, the use of alkylating agents-based regimens in 57%, CHOP/like in 15% and bendamustine in 15%. Patient enrollment and data collection on actual therapy, response and follow-up and histological revision are currently ongoing. Conclusions The NF10 confirms that a web based world-wide cooperation allows the collection of a relevant and quite complete set of data in a limited period of time, providing a platform for future prognostic and therapeutic studies. Disclosures: Federico: MedImmune: Research Funding.