ALBERT

Description: Abstract 2673 Introduction: Follicular Lymphoma International Prognostic Index 2 (FLIPI-2) is a widely accepted tool for risk assessment of follicular lymphoma (FL), which is based on age, hemoglobin level, presence of bone marrow (BM) invasion, tumor size, and b2-microgloblin levels. Although it is easy to evaluate in clinical practice, it is a combination of tumor burden and patient physical condition, and a simple and powerful biomarker reflecting the tumor burden and its character is still not established. LR11 (also called SorLA or SORL1) was identified and characterized as a regulator of uPAR function through complex formation with uPAR. We have identified that serum soluble LR11 (sLR11) levels are significantly elevated in patients with acute leukemia and B cell lymphomas, and are associated with tumor burden and BM invasion (Sakai et al 2012). We have also found that high sLR11 levels had a significant negative prognostic impact on progression-free survival (PFS) in FL. Therefore, we have retrospectively evaluated the clinical characteristics of sLR11 and its prognostic impact on FL, in a larger patient cohort. Patients and Methods: Sixty-one patients with FL treated at Chiba University Hospital and affiliated hospitals from 2002 to 2012 were evaluated. The majority of patients were treated by the R-CHOP regimen (rituximab 375 mg/m2 on day 1; cyclophosphamide, 750 mg/m2 on day 1; adriamycin, 50 mg/m2 on day 1; vincristine, 1.4 mg/m2 on day 1; and prednisolone, 100 mg/body on day 1–5). Serum sLR11 levels were measured by ELISA method. Patient laboratory data and treatment outcome were obtained retrospectively. Results: Serum sLR11 levels of patients with lymphoma were significantly increased (mean ± SD: 19.4 ± 17.1 ng/ml) compared with those of normal control subjects (8.8 ± 1.79 ng/ml, P

Description: Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases in terms of morphology, immunohistochemistry and molecular features. The t(14;18)(q32;q21) translocation juxtaposes the BCL2 gene, normally located at 18q21, with the IGH locus on 14q32. The t(14;18)(q32;q21) occurs in about 80-90% of follicular lymphomas and about 25-30% of de novo DLBCLs. On the other hand, the t(8;14)(q24;q32) translocation juxtaposes the c-MYC protooncogene, which is located at 8q24, to the immunoglobulin heavy chain (IGH) gene, located at 14q32, resulting in deregulated expression of c-MYC. t(8;14)(q24;q32) has been found in 80-90% of Burkitt lymphoma cases and in 5-15% of DLBCL cases. B-cell lymphoma having both t(14;18) and 8q24, so called double hit lymphoma (DHL), is rare. The pathological diagnosis in most cases of DHL is B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). Patients with DHL have elevated serum LDH levels, advanced stage, bone marrow involvement, extranodal involvement and the presence of B symptoms. In the present study, we evaluated the clinicopathological characteristics and prognoses of patients with BCLU with DHL. Patients and Methods: A total of 368 patients with DLBCL and BCLU were treated from 2007 to 2013. Chromosomal data were available in 195 of the 368 patients. Pathologic evaluation of the materials from each patient was performedat several central review meetings by six hematopathologists in the ALTSG pathology review board. Patients were treated with cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone (CyclOBEAP) regimen or CHOP regimen. Rituximab was administered to all patients. The median follow-up period was 44 months (range, 12-61 months). Results: t(14;18) + 8q24 dual translocation was seen in 18 (9.2 %) of the 195 patients with DLBCL and BCLU. There were 12 males and 6 females, with a median age of 62 (range, 47-76) years. Stage III/IV was found in 56%, bone marrow infiltration was found in 39％, central nervous system (CNS) infiltration was found in 17％, and high risk of international prognostic index (IPI) was found in 67％. Among the 18 patients with the DHL, extranodal sites of disease were bone marrow (7 patients), CNS (3 patients), pleural effusion (5 patients), and gastrointestinal tract (3 patients). Furthermore, 8 patients had at least two extranodal localizations. Immunophenotyping analysis (CD20, CD5, CD10, BCL2, BCL6, MUM1, Ki-67) was performed and showed BCLU with a germinal center type in all cases. Ki-67 staining ranged from 30-90%. All lymphoma cells were positive for CD20 and negative for CD5. CD10, BCL2, BCL6, and MUM1 were positive in 89%, 75%, 88%, and 19%, respectively. The 4-year overall survival (OS) rate was 72% among the patients with dual translocation (n=18) and 75% among the patients in the other chromosomal abnormalities group (n=177). The 4-year progression-free survival (PFS) rate was 52% among the patients with the dual translocation and 71% among the patients in the other chromosomal abnormalities group. The 4-year OS rate of the stage I/II and stage III/IV groups was 100% and 47%, respectively (P=0.016). We next examined the survival curve of patients in whom data on serum LDH levels were available. The 4-year OS rates of the high (〉2N) and low LDH groups (

Description: Abstract 5104 Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of malignant lymphoma, characterized by the selective growth of lymphoma cells within the lumina of vessels in various organs. Although recent reports showed that prompt and accurate diagnosis lead to better outcomes, absence of typical clinical manifestations and its aggressive behavior frequently makes it difficult. LR11 (also called SorLA or SORL1) is a type I membrane protein, from which a soluble form (sLR11) is released by proteolytic shedding. sLR11 is originally known to be a biomarker of carotid intima-media thickness. We have recently found that LR11 is expressed on human leukemia cell lines, and sLR11 is released in its culture medium. Serum sLR11 levels are significantly elevated in patient serum samples with acute leukemia and B cell lymphomas, and are associated with tumor burden and bone marrow invasion. Based on these findings, we hypothesized that LR11 may be also expressed and released from IVLBCL cells; therefore we evaluated its clinical importance in IVLBCL. Materials and methods: Serum samples and paraffin embedded tumor specimens were obtained from 6 patients who were histologically diagnosed as IVLBCL from 2009 to 2012. Specimens were subjected to immunostaining using anti-LR11 antibody, and serum sLR11 levels were measured by ELISA method. Patient laboratory and clinical data were collected retrospectively. Also, serum samples from 75 healthy volunteers, and 10 patients with collagen diseases presenting similar clinical manifestations as IVLBCL were analyzed. Results: Tissue samples of IVLBCL were obtained by bone marrow biopsy (N=2), transbronchial lung biopsy (N=2), and random skin biopsy (N=2). Biopsy specimens showed that cytoplasm of IVLBCL cells were specifically immunoreacted against the anti-LR11 antibody (Figure 1). Median serum sLR11 level of IVLBCL patients was 86. 0 ng/ml (mean ± SD: 201. 8 ± 260. 0 ng/ml), which was significantly elevated than those of healthy volunteers (median: 8. 4 ng/ml, mean±SD: 8. 8 ± 1. 8 ng/ml, p

Description: Abstract 2795 Peripheral T-cell lymphoma (PTCL) is more aggressive and has a poorer prognosis than diffuse large B-cell lymphoma (DLBCL). In particular, PTCL, not otherwise specified (PTCL, NOS) is not responsive to conventional chemotherapies. The usefulness of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has been reported, although a recent study did not confirm this result. More recent study, however, suggested that intensified regimens may indeed yield superior results to CHOP. We previously administered the CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen to patients with DLBCL, and reported its safety and efficacy. nm23-H1 was originally identified as a protein that was expressed at a lower level in metastatic cancer cells. The nm23 genes play critical roles in cellular proliferation, differentiation, oncogenesis, and tumor metastasis. We previously reported that the serum nm23-H1 level was significantly higher in patients with aggressive lymphoma than in healthy controls, and that a high nm23-H1 level was associated with poor prognosis in patients with aggressive lymphoma. We previously examined cytoplasmic nm23-H1 expression in DLBCLs and found that the serum and cytoplasmic nm23-H1 levels were significant prognostic factors in DLBCLs. Here, we report the results of a multicenter phase II study of the CyclOBEAP regimen for patients with PTCLs [anaplastic large-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AILT), and PTCL, NOS]. This was a prospective, single-arm phase II trial in the Adult Lymphoma Treatment Study Group (ALTSG) in Japan. Patients were enrolled in the study between April 1998 and March 2006. Patients aged between 18 and 60 years who were in the low-intermediate (L-I), high-intermediate (H-I), or high (H) risk groups, were eligible for this study. The CyclOBEAP regimen was administered over a total period of 12 weeks. In the CyclOBEAP regimen, the dose intensities of cyclophosphamide, doxorubicin, and vincristine are equal to or higher than those in the CHOP regimen, and etoposide and bleomycin were added to the CHOP regimen. There were 84 eligible patients and the median age was 54 years. The median follow-up period was 82 months. A complete response was achieved in 77 patients (92%). The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 69%. The 5-year OS was 93% among the ALCL patients, 74% among the AILT patients, and 63% among the PTCL,NOS patients. Further evaluation of the 5-year PFS among the PTCL, NOS and AILT patients (n=70) according to the international prognostic index showed that the 5-year PFS in patients with L-I, H-I or H risk was 77.4%, 48.6% and 25%, respectively (P=0.011). When the patients were divided according to the prognostic index for PTCL (PIT), the 5-year OS and PFS rates did not significantly differ among the risk groups. We next examined the survival curve of patients with PTCL in whom soluble interleukin-2 receptor data were available. The 5-year survival rates of the high (≧2000 IU/ml) and low soluble interleukin-2 receptor groups (

Description: Abstract 1581 Introduction: LR11 is a type I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding. It plays a key role in the migration of undifferentiated vascular smooth muscle cells, and circulating sLR11 is a known biomarker of carotid intima-media thickness. We have recently found that LR11 is specifically and highly expressed on the cell surface of acute leukemia cells in addition to normal leukocytes. Furthermore, patients with various hematological malignancies showed significantly high serum sLR11 levels especially in B-cell acute lymphoblastic leukemia. Serum sLR11 level has a significant association with remission and survival rate in patients with acute leukemia (Ohwada et al. 2010 ASH annual meeting). Based on these findings, we have retrospectively evaluated the clinical importance of serum sLR11 in patients with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Patients and Methods: Fifty-one patients with DLBCL and 23 patients with FL treated at Chiba University Hospital between 2002 and 2011 were evaluated. The majority of patients were treated by the R-CHOP regimen (rituximab 375 mg/m2 on day 1; cyclophosphamide, 750 mg/m2 on day 1; adriamycin, 50 mg/m2 on day 1; vincristine, 1.4 mg/m2 on day 1; and prednisolone, 100 mg/body on day 1–5). Patient biopsy specimens were subjected to immunostaining using anti-LR11 antibody. Serum sLR11 levels were measured by ELISA. Patient laboratory data and treatment outcome were obtained retrospectively. Results: Immunostaining of paraffin-embedded lymphoma tissue revealed that the cytoplasm of lymphoma cells of both DLBCL and FL specifically reacted against the anti-LR11 antibody. Furthermore, serum sLR11 levels of patients with lymphoma were significantly increased (DLBCL: 17.4±14.7 ng ml−1, FL: 22.7±25.5 ng ml−1) compared with those of normal control subjects (8.8±1.79 ng ml−1, P