Ocular Adnexal Lymphomas: Experience of Single Center

Abstracts lymphoma and therefore helpful in differential diagnosis. In this study, we describe 5 cases of extramedullary plasmacytoma arising in immunocompetent individuals that were diffusely positive for Epstein-Barr virus encoded small RNA by in situ hybridization. These tumors were characterized by a diffuse proliferation of mature appearing plasma cells intermixed with a brisk reactive, CD8+, TIA1+ T-cell infiltrate. Long-term follow-up was available for all patients (median 44.1 months). All patients were alive and free of disease at last follow up. It is essential to appropriately identify these neoplasms, which we have designated as EBV+ plasmacytoma in immunocompetent patients (EPIC), and to distinguish these tumors from plasmablastic lymphoma as the latter diagnosis is associated with a poor prognosis and patients require much more aggressive therapy.

38.0%, respectively), except against VL-CEM (0.2%). Finally, we evaluated cytotoxicity against CD20-low tumor cells. CAR-T cells lysed RRBL1 which is a cell line established from a DLBCL patient who exhibited CD20-negative phenotypic changes after repeated chemotherapy with rituximab (47.83% of lysis at E:T ratio 10:1) and lysed the primary cells isolated from patients with mAb therapyrefractory CLL, albeit the CD20 expression was almost negatively converted. (35.50.63% of lysis at E:T ratio 10:1) Conclusions: CAR-T cells could recognize and lyse cells expressing very low levels of the target antigen and were activated and expanded upon stimulation. CD20 CAR-T cell therapy may also be applicable to the treatment of CD20 down-regulated, mAb therapy resistant tumors.

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504 Development of a novel humanized anti-CD20 chimeric antigen receptor; Effect on the CD20 down-regulated and mAb therapy resistant tumor cells 1

1

Keisuke Watanabe, Seitaro Terakura, Susumu Uchiyama,2 Kazuyuki Shimada,1 Akihiro Tomita,1 Tetsuya Nishida,1 Makoto Murata,1 Tomoki Naoe,1 Hitoshi Kiyoi1 1

Department of Hematology and Oncology, Nagoya university graduate school of medicine; 2Division of Advanced Science and Biotechnology, Osaka university graduate school of medicine

Background: In chimeric antigen receptor transduced T-cell (CAR-T cell) therapy, setting of the target antigen is critical in terms of both the efficacy and the possible adverse effects. However, how low expressing antigen CAR-T cells can recognize and lyse is unclear. Methods: In this study, we generated a novel CAR consisting of anti-CD20 single chain variable fragments linked to a CD3-zeta chain, a CD28 costimulatory domain, and a truncated epidermal growth factor receptor (tEGFR) as a transduction marker. CD8 positive T cells were activated with anti-CD3/28 beads, transduced with the CAR, enriched by selection with anti-EGFR mAb, and expanded by stimulation with gamma-irradiated B-lymphoblastoid cells. Results: To determine the threshold expression level of CD20 antigen to induce cytotoxicity, we performed 51Cr release against 30 clones of CD20 transduced CCRF-CEM (CD20-CEM) expressing various levels of CD20 (CD20 ¼ 240-230,546 molecules/cell). CAR-T cells lysed CD20-CEMs equally well from low to high level of CD20 (CD20 ¼ 5,172 molecules or more, 40-60% of lysis at E:T ratio of 10:1), and lysed the clone expressing the lowest level of CD20 (240 molecules, 22.82% of lysis). Next, we performed intracellular IFN-gamma production upon the stimulation with four representative CD20-CEM clones depicted from the 30 clones; CD20 very low CEM (VL-CEM) (240 molecules), low (L-CEM) (26,990 molecules), mid (M-CEM) (91,567 molecules), and high (H-CEM) (142,722 molecules). CAR-T cells produced IFN-g equally well (L-CEM, 45.9%, M-CEM, 35.4% and H-CEM,

Ocular Adnexal Lymphomas: Experience of Single Center Melda Cömert Özkan,1 Melis Palamar Onay,2  lu,1 Mine Hekimgil,3 Nazan Özsan,3 Murat Tombulog 1 Güray Saydam, Fahri S¸ahin1 1

Ege University, School of Medicine, Department of Hematology;

2

Ege University, School of Medicine, Department of Ophtalmology;

3

Ege University, School of Medicine, Department of Pathology

Context: Ocular adnexal lymphomas (OALs) are a rare manifestation of non-Hodgkin lymphomas (NHLs), accounting for 1% to 2% of all NHLs and about 8% of the extranodal lymphomas, however the incidence of OAL has increased by approximately 6% annually in last 20 years. Objective: Determining OALs frequency and optimal treatment in our clinic and evaluating the outcomes. Design: Eighteen OAL cases diagnosed in our pathology department between 2004-2014 was evaluated retrospectively in terms of disease localization, type of treatment, and outcomes based on our hospital records. Results: Six (33.3%) of the cases were marginal zone lymphoma (MZL) (3 ENMZ5L, 3 NMZL), 5 (27.8%) mantle cell lymphoma (MCL) (3 blastoid variant), 3 (16.7%) diffuse large B cell lymphoma (DBBHL), 2 (11.1%) follicular lymphoma and 1 (5.6%) was lymphoblastic lymhoma. 15 cases were followed in our clinic. Eight (53.3%) cases were primary OAL, 5 (33.3%) were initial sign of systemic lymphoma and 2 (13.3%) cases were diagnosed in the course of lymphoma. 7 primary OAL cases were treated with radiation therapy, systemic lymphomas and one of primary lymphoma which was bulky disease were treated with chemotherapy. Two cases (in the course of FL and primary ENMZL) had relapsed diseases. Conclusion: However more than one-half of the cases of OALs are mucosa-associated lymphoid tissue (MALT) lymphomas, mantle cell lymphoma especially blastoid variant and extranodal marginal zone lymphoma was relatively higher in our clinic. Because of high relaps rates, systemic treatment can be considered particulartly in bulky and/or destructive diseases. Radiotherapy should be a part of therapy in selected cases.

Clinical Lymphoma, Myeloma & Leukemia June 2015

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