scholarly journals Helical Irradiation of the Total Skin with Dose Painting to Replace Total Skin Electron Beam Therapy for Therapy-Refractory Cutaneous CD4+ T-Cell Lymphoma

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chen-Hsi Hsieh ◽  
Pei-Wei Shueng ◽  
Shih-Chiang Lin ◽  
Hui-Ju Tien ◽  
An-Cheng Shiau ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
Organ Dose ◽  
T Cell Lymphoma ◽  
Cd4 T Cell ◽  
Whole Body ◽  
Dose Painting ◽  
The Mean ◽  
Painting Techniques

A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS) and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB) technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

scholarly journals TET2 Mutation Associated with Organ Infiltrations in ATLL

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1345-1345
Author(s):  
Takuro Kameda ◽  
Kotaro Shide ◽  
Ayako Kamiunten ◽  
Yuki Tahira ◽  
Keiichi Akizuki ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Analysis ◽  
T Cell ◽  
Double Mutant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cd4 T Cell ◽  
Whole Body ◽  
Tet2 Mutation

Abstract Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma that is caused by HTLV-1. The prognosis of acute and lymphomatous variants of ATLL is poor, ranging from 2 weeks to >1 year. Compared to other types of malignant lymphomas, the organ infiltration is frequently observed in ATLL (Yamada et al. Leuk Lymphoma 1997). We previously reported the landscape of genetic mutations in ATLL, and showed that various mutations occurred in the TCR-NFκB pathway in more than 90% of ATLL cases (Kataoka et al. Nat Genet 2015). These somatic mutations are thought to develop ATLL in combination with viral genes such as HTLV-1 bZIP factor (HBZ). Among them, mutations in TET2, an epigenetic regulator, was observed in about 10% of ATLL cases. Higher frequencies inTET2 mutation was reported in other types of peripheral T-cell lymphoma (PTCL); it was observed in about 80% of angioimmunoblastic T-cell lymphoma (AITL) and in about 50% of PTCL, not otherwise specified. In PTCL, it has been reported that additional mutations in lymphoid progenitors derived from TET2 mutated hematopoietic stem cells cause increased cell proliferation and anti-apoptosis, leading to the disease progression. In ATLL, the role of TET2 mutation in disease progression is still unknown. In this study, we investigated the role of TET2 mutation in ATLL using mouse model and acute and lymphomatous variant ATLL cohort. Materials and methods: As an animal model of HTLV-1 infection or ATLL, transgenic mice expressing HBZ under the control of the mouse CD4 promoter (HBZ-Tg) were generated with C57BL/6 background. Heterozygous TET2 knock-down mice (TET2KD) were generated with C57BL/6 background by gene trapping (Tang et al. Transgenic Res 2008; Shide et al. Leukemia 2012). HBZ-Tg/TET2KD compound mice (double mutant) were generated by crossing them. HBZ-Tg, TET2KD, and double mutant mice were investigated by cell counts, organ weight, FACS analysis, pathological analysis, and survival analysis. The relationship between the TET2 mutation status and the clinical feature was investigated using our acute and lymphomatous variant ATLL cohort (n=115). Result: At 12 months, compared to wild type mouse (WT), sporadic splenomegaly and lymphadenopathy were observed in HBZ-Tg. No significant increase was observed in peripheral blood (PB) leukocyte and mononuclear cell (MNC) of BM and spleen, but an increase was observed in the estimated whole body MNC (Femur x 100/6 + spleen) (WT vs. HBZ-Tg; estimated whole body MNC (x106 cells/body), 416±162 vs. 621±147, p=0.01). In FACS analysis, the frequency of CD4+ T-cell was increased in PB, spleen, and BM (WT vs. HBZ-Tg; PB-CD4+ T-cell%, 4.9±0.9 vs. 28.2±22.8, p<0.05; spleen CD4+ T-cell%, 10.3±3.1 vs. 18.2±3.3, P<0.01; BM-CD4+ T-cell%, 1.2±0.6 vs. 2.5±1.1, p<0.05), and the estimated whole body CD4+ T-cell count was also increased (WT vs. HBZ-Tg; CD4+ T-cells (x106 cells/body) 13.6±7.6 vs. 41.9±24.4, p<0.01). In the survival analysis, compared to WT, the shortened overall survival (OS) was observed in HBZ-Tg (median survival time (MST, month), unreached vs. 11.1, p<0.01). In pathological analysis, HBZ-Tg showed increased leukocyte infiltration to various organs such as lung and liver, and the infiltrated cells were mainly composed of T-cells. In the lung, in addition to the cell infiltration, alveolar edema was observed, which was presumed to be the main cause of death. Next, to elucidate the role of TET2 mutation in ATLL, the double mutant was analyzed. At six months, compared to HBZ-Tg, no increase was observed in the number of PB leukocyte, spleen-MNC, and BM-MNC, and also in the frequency and the number of CD4+ T-cells in PB, spleen and BM. However, in pathological and survival analysis, the double mutant showed severe cell infiltration in lung and liver and demonstrated inferior OS (median OS (month), 11.1 vs. 6.0, p<0.05). Further, the double mutant showed increased frequency of CD103 (integrin alpha E), an adhesion molecule, expressing cells (CD4+CD103+% in spleen; 6.7±1.0 vs. 10.9±1.9, p<0.05). In the acute and lymphomatous variant ATLL cohort analysis, genetic and clinical investigation revealed that organ infiltration detectable by imaging studies was frequently observed in TET2 mutated patients (WT-Pt (n=100) vs. TET2 mutated-Pt (n=15); extra nodular lesion, 78/100 vs. 14/15). Conclusion: In both mice model and human cohort, TET2 mutation exacerbated organ infiltration of ATLL cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi

2021 ◽  
Vol 11 ◽  
Author(s):  
Laura Ballotta ◽  
Pier Luigi Zinzani ◽  
Stefano Pileri ◽  
Riccardo Bruna ◽  
Monica Tani ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Clinical Trial Registration ◽  
Prospective Phase ◽  
Bcl2 Protein

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified.Clinical Trial Registrationwww.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).

Small intestinal CD4+ T-cell lymphoma: a rare distinctive clinicopathological entity associated with prolonged survival

2007 ◽  
Vol 451 (6) ◽  
pp. 1091-1093 ◽  
Author(s):  
Magali Svrcek ◽  
Laurent Garderet ◽  
Virginie Sebbagh ◽  
Michelle Rosenzwajg ◽  
Yann Parc ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cd4 T Cell ◽  
Prolonged Survival ◽  
Small Intestinal

scholarly journals Indolent Small Intestinal CD4+ T-cell Lymphoma Is a Distinct Entity with Unique Biologic and Clinical Features

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68343 ◽  
Author(s):  
Elizabeth Margolskee ◽  
Vaidehi Jobanputra ◽  
Suzanne K. Lewis ◽  
Bachir Alobeid ◽  
Peter H. R. Green ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cd4 T Cell ◽  
Distinct Entity ◽  
Small Intestinal

A Phase I Open Label Dose Escalation Study To Evaluate MEDI-507 in Patients with CD2-Positive T-Cell Lymphoma/Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2727-2727 ◽  
Author(s):  
Deborah A. Casale ◽  
Nancy L. Bartlett ◽  
David D. Hurd ◽  
Francine Foss ◽  
Barbara Pro ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
Dose Escalation ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
Lymphocytic Leukemia ◽  
T Cell Lymphoma ◽  
Cell Recovery ◽  
Open Label ◽  
Dose Escalation Study

Abstract This ongoing multicenter study is a Phase I trial with MEDI-507 (Siplizumab) [a humanized IgG1k class monoclonal antibody that binds to the CD2 receptor on human T- and NK-cells] to determine the maximum tolerated dose (MTD) or the optimum biologic dose (OBD) in patients with relapsed/refractory CD2-positive T-cell lymphoma/leukemia [CD2-positive adult T-cell leukemia (ATL), cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), and large granular lymphocytic leukemia (LGL).] Open label 3+3 dose escalation was conducted in which patients receive bi-weekly infusions of MEDI-507 over 3 consecutive days at total doses of 0.7 mg/kg, 3.4 mg/kg or 4.8 mg/kg. Predose and serial MEDI-507 pharmacokinetics (ELISA) at Visit 2 and anti MEDI-507 antibodies (ELISA), peripheral blood total T-Cell and CD2-positive T-cells (flow cytometry), and C3 and C4 complement are obtained for each patient. Patients are followed for one year after their last dose of MEDI-507 for tumor assessment and CD2-positive T-cell recovery. 16 patients have been enrolled: 3 (0.7 mg/kg); 9 (3.4); 4 (4.8). Three additional patients were added to the 3.4 mg/kg cohort to replace patients who progressed early and one patient with tumor lysis syndrome. Diagnoses of the 16 patients: PTCL (9), CTCL (6) and NK-LGL (1). Frequent adverse events reported, to date, are infusion reaction (7/16) patients; hypertension (4/16); lymphopenia (4/16); fatigue (4/16) and leukopenia (3/16). Two DLT’s have been observed. The first, erythematous confluent dermatitis, occurred in one patient at 3.4 mg/kg and the cohort was expanded with eventual dose escalation. The second, pulmonary edema, occurred in one patient at 4.8 mg/kg and the cohort is currently being expanded without further DLT identified to date. Two responses have been observed, one PR in an NK-LGL patient at 3.4 mg/kg and one CR in a PTCL patient at 3.4 mg/kg. MEDI-507 has been well tolerated and shown anti-tumor activity. Dosing will change to weekly dosing with dose escalation (3+3) starting at 1.2 mg/kg as 0.8 mg/kg was seen to be safe in the single center study. MTD and/or OBD have not been determined.

Pralatrexate (PDX) IS Active in Cutaneous T-Cell Lymphoma: Preliminary Results of a Multi-Center Dose-Finding Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1569-1569 ◽  
Author(s):  
Steven M. Horwitz ◽  
Madeleine Duvic ◽  
Youn Kim ◽  
Jasmine M. Zain ◽  
Mary Jo Lechowicz ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Tumor Lysis Syndrome ◽  
T Cell Lymphoma ◽  
Hematological Toxicity ◽  
Cutaneous T Cell Lymphoma ◽  
Phase 1 Study ◽  
Toxic Dose ◽  
Aggressive Lymphomas

Abstract Background: Pralatrexate (PDX) is a novel targeted antifolate that is designed to accumulate preferentially in cancer cells. Pralatrexate has demonstrated activity at a range of doses in patients (pts) with relapsed/refractory T-cell lymphoma. The maximum tolerated dose (MTD) in a trial of pts with aggressive lymphomas was 30 mg/m2 weekly for 6 of 7 weeks. In that Phase 1 study, responses were seen in pts with cutaneous T-cell lymphoma (CTCL). To further explore this activity, we designed PDX-010, a multi-center, open-label, Phase 1 study of pralatrexate with vitamin B12 and folic acid in pts with relapsed/refractory CTCL. As CTCL is often a more indolent disease than peripheral T-cell lymphoma and treatment paradigms use maintenance approaches, we sought to identify the least toxic dose and schedule with activity for this distinct pt population through a dose de-escalation scheme. Methods: Eligible pts were required to have mycosis fungoides (MF), Sézary syndrome (SS), or cutaneous anaplastic large cell lymphoma (ALCL), and progression of disease (PD) after ≥ 1 systemic therapy. The dosing scheme employed 2 schedules: a 3 out of 4 week schedule and a 2 out of 3 week schedule. Doses are reduced in sequential cohorts based on toxicity. Optimal dose and schedule is defined as evidence of anti-tumor activity without Grade (Gr) 4 hematological toxicity, Gr 3–4 infection, or febrile neutropenia. Responses in skin are investigator-assessed using the modified severity weighted assessment tool (mSWAT). Results: From August 2007 to August 2008, 23 pts have enrolled, 17 of whom are evaluable for safety and response. The 17 evaluable pts, 15 with MF, 1 with SS, and 1 with ALCL, were enrolled into 4 cohorts: 30 mg/m2 3 of 4 weeks (n=2), 20 mg/m2 3 of 4 weeks (n=3), 20 mg/m2 2 of 3 weeks (n=7), and 15 mg/m2 3 of 4 weeks (n=5). These pts were heavily pretreated with a median of 6 prior regimens (range 1–25), and a median of 3.5 prior systemic regimens (range 1–9). Dose-limiting toxicities (DLTs) to date have included Gr 2 acute renal failure (1), Gr 3 joint stiffness/muscle weakness (1), and Gr 2–3 stomatitis/mucositis (4). The most common treatment-related AEs include mucositis (10 patients [59%]), nausea (8 patients [47%]), and fatigue (7 patients [41%]). Treatment-related SAEs occurred in 3 pts: stomatitis (Gr 2) at pralatrexate 20 mg/m2 2 of 3 weeks; chills (Gr 1) and exfoliative dermatitis (Gr 2) at pralatrexate 20 mg/m2 2 of 3 weeks; and hypoalbuminemia (Gr 3) and tumor lysis syndrome (Gr 3) at pralatrexate 20 mg/m2 3 of 4 weeks. To date of the 17 evaluable pts, 9 have achieved a response (53%), including partial response (PR) in 7 pts, and complete response (CR) in 2 pts (1 progressed rapidly off treatment). In addition, 6 pts had SD. Eight of the responding pts had MF, and the pt with ALCL had a CR. Seven of the 17 pts remain on treatment, including 3 pts who have been on treatment for 8, 8, and 9 months, respectively. Conclusion: In this preliminary report, pralatrexate shows marked clinical activity in the treatment of CTCL at much lower doses than those used for aggressive lymphomas. Responses have been observed in pts who had previously received up to 8 prior treatment regimens. This study is ongoing to identify a dose and schedule of pralatrexate that can result in maintained responses with minimal toxicity for pts with CTCL.

A Case of ALK+ Anaplastic Large T Cell Lymphoma (ALCL) with Lymphomatous Meningitis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5226-5226
Author(s):  
Bongi A. Rudder ◽  
Nidhi Mishra ◽  
Albert S. Braverman ◽  
Michael Geraghty ◽  
Elpidio Jimenez
Keyword(s):  
T Cell ◽  
Skin Disease ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Whole Body ◽  
Axillary Lymph ◽  
Lymphomatous Meningitis ◽  
Beam Radiation ◽  
Abducens Paralysis ◽  
Cutaneous Nodule

Abstract Abstract 5226 Background: Anaplastic large T cell lymphoma may present with indolent cutaneous T cell infiltration, progressing to more aggressive skin disease and systemic involvement. In adults lymphomatous meningitis is very rare complication. Case Report: A 62 year old Jamaican woman had been diagnosed with biopsy proven psoriasis when 42 years of age. Ustekinumab had been initiated without effect two months prior to her presentation to us. A new cutaneous nodule on her left neck was then found, shave biopsy of which revealed psoriasiform dermatitis with epidermotropism, suspicious for early patch stage mycosis fungoides. The lesion was CD30+, suggestive of ALCL and was positive for ALK. Positron emission tomography revealed an SUV of 6.0 in the neck mass, but lymph nodes in all regions had an SUV of <2.3. Axillary lymph node biopsy, bone marrow biopsy and flow cytometry were negative. Local electron beam radiation was administered to the left supraclavicular space with complete resolution of the cutaneous nodule. About 2 months following completion of radiation therapy she noted anorexia, 30 lb weight loss, night sweats and left hip pain. Physical examination revealed a sick woman, with whole body scaling red-brown macules and plaques. CBC was normal except for Hb of 10 g/dl, platelets 453,000/dl. Hepatic and renal function studies were normal. ESR was 84 mm/hr, lactic dehydrogenase 670 IU (reference range 300–600 IU) and calcium 15.1 mg/dl. HTLV1, HIV, hepatitis panel and anti-nuclear antibody serologies were negative. Computer automated tomography of the pelvis demonstrated 6×2×8 cm soft tissue mass on the sacrum invading left sacro-iliac joint and ilium. Biopsy revealed ALCL, positive for CD43, CD2dim, CD7dim, CD30, and nuclear and cytoplasmic ALK1, while negative for CD43, 3, 4, 5, 8, 19,20, 34, 138, PAX5, AE1/AE3, Cam5, S100 and TdT. The mass was irradiated with alleviation of pain, but cutaneous nodules progressively appeared and continuous fever developed with negative blood cultures. There was increasing confusion, blurred vision and bilateral abducens paralysis. Magnetic resonance imaging of the head and spine revealed dural enhancement and multiple extra- and intercranial interosseous masses, one of which involved the posterior sella turcica. Cyclophosphamide, doxorubicin, vincristine and prednisone were initiated; lumbar puncture was refused. Within 2 days after treatment initiation the cutaneous nodules disappeared, fever subsided, the left abducens palsy resolved completely while the right improved. Conclusion: Our patient's long standing indolent skin disease abruptly progressed to cutaneous and systemic ALCL, with evidence of lymphomatous meningitis. The response of her abducens palsies and other CNS findings to systemic chemotherapy alone suggests that her meningeal involvement may have arisen from that of adjacent bones. Involvement of CNS in ALK positive systemic anaplastic large cell lymphoma is rare and reported in mainly pediatric cases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Circulating Lymphoma Cells in Mycosis Fungoides/Sezary Syndrome Show Heterogeneity of the Cell-of-Origin and Variable PD-1 Expression By Flow Cytometric Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1624-1624
Author(s):  
Mariko Yabe ◽  
Natasha Lewis ◽  
Qi Gao ◽  
Allison Sigler ◽  
Jeeyeon Baik ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cd4 T Cell ◽  
Cell Of Origin ◽  
Lymphoma Cells ◽  
T Cell Subset ◽  
Subset Analysis ◽  
Flow Cytometric

Abstract Introduction: Mycosis fungoides (MF) is an epidermotropic primary cutaneous T-cell lymphoma. Its leukemic variant is recognized as Sezary syndrome (SS), although a study suggests that MF and SS may be distinct entities arising from different T-cell subsets; effector memory T-cells and central memory T-cells, respectively (Campbell JJ et al. Blood. 2010;116(5):767-771). Recent studies show bright PD-1 (T follicular helper (TFH)-like), and CD25/FOXP3 (Treg-like) expression in a subset of MF/SS cases by immunohistochemistry, and these findings raise the possibility that the cell-of-origin of MF/SS may be heterogeneous (Cetinozman F et al. Arch Dermatol. 2012;148(12):1379-1385, Prince HM et al. J Am Acad Dermatol. 2012;67(5):867-875, Satou A et al. Histopathology. 2016;68(7):1099-1108). In order to address this question comprehensively, we evaluated the expression levels of PD-1 on lymphoma cells of MF/SS patients by flow cytometry in peripheral blood (PB), and the results were compared to other T-cell lymphomas including angioimmunoblastic T-cell lymphoma (AITL). We also performed extensive flow cytometric immunophenotyping to algorithmically assess cell-of-origin of MF/SS with a subset of patients (Maecker HT et al. Nat Rev Immunol. 2012;12(3):191-200). Methods: Patients who were diagnosed with T-cell lymphoma at Memorial Sloan Kettering Cancer Center between August 2015 and August 2018, and have circulating lymphoma cells in PB were selected for this study. Diagnosis of MF/SS was confirmed by skin biopsy along with the clinical presentation. PD-1 expression levels on lymphoma cells in PB were evaluated by 10-color flow cytometry including anti-CD279 (PD-1) antibody. Immunophenotyping to assess cell-of-origin of lymphoma cells (T-cell subset analysis) was performed with 3 tube/10-color flow cytometry, using the following antibodies: CD3, CD4, CD8, CD25, CD27, CD45RA, CD45RO, CD127, CD279, HLA-DR, CCR4, CCR6, CCR7, and CXCR3. Results: Our study group is composed of 82 patients, including 34 MF/SS, 22 AITL, 2 anaplastic large cell lymphoma, ALK-negative (ALCL, ALK-), 8 adult T-cell leukemia/ lymphoma (ATLL), 5 peripheral T-cell lymphoma, NOS (PTCL-NOS), 5 T-cell large granular lymphocytic leukemia (T-LGL), and 6 T-cell prolymphocytic leukemia (T-PLL). The expression levels of PD-1 of lymphoma cells of the patients with MF/SS were widely variable (mean fluorescence intensity (MFI); Mean 949.0; range 101.0 - 3188.6) (Fig 1). 32.4% (11/34) of MF/SS cases showed high PD-1 expression equivalent to that of AITL cases. T-cell subset analysis to assess cell-of-origin was performed in 14 patients, including 4 patients with MF and 10 patients with SS (Table 1). While routine flow cytometric analysis showed similar immunophenotype other than the variation of PD-1, by flow cytometric T-cell subset analysis, we identified 3 patients with lymphoma cells showing T follicular helper (TFH) immunophenotype with CCR4+/CXCR3-/CCR6- and bright CD279 expression (case 2, 6, 8) (Table 2). Lymphoma cells of 8 patients showed effector memory CD4+ T-cell immunophenotype defined as CCR7-/CD45RA- (case 1, 3, 4, 5, 9, 10, 12, 13). Among these 8 patients, 2 patients had a subset of lymphoma cells showing central memory CD4+ T-cell immunophenotype defined as CCR7+/CD45RA- (case 5 and 12), and 2 patients had a subset with effector CD4+ cell immunophenotype defined as CCR7-/CD45RA+ (case 9, 13). 2 patients (case 7, 14) showed central memory CD4+ T-cell immunophenotype only, and 1 patient showed effector CD4+ T-cell immunophenotype only (case 11) (Table 2, Fig 2, 3). No cases showed Treg immunophenotype. The small sample size limited any subset analysis but we did not see obvious association between cell-of-origin of lymphoma cells and clinical features including prognosis, nodal presentation, number of circulating tumor cells, and histological findings in this study with limited number of cases. Conclusions: Lymphoma cells in MF/SS show marked heterogeneity of expression of PD-1 including clear subset arising from TFH. This suggests MF/SS may represent multiple biological entities. Further studies will be necessary to investigate the clinical significance of cell-of-origin of MF/SS. Disclosures Yabe: Y-mAbs Therapeutics: Consultancy. Moskowitz:ADC Therapeutics: Research Funding; Incyte: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Takeda: Honoraria; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Horwitz:Infinity/Verastem: Consultancy, Research Funding; Trillium: Consultancy; Innate Pharma: Consultancy; Portola: Consultancy; Kyowa-Hakka-Kirin: Consultancy, Research Funding; Aileron Therapeutics: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Spectrum: Research Funding; Corvus: Consultancy.

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