{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:44:17Z","timestamp":1789015457491,"version":"build-2803163510"},"reference-count":112,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ADC Therapeutics, Beigene, Miragen, Seattle Genetics, Merck, Bristol-Myers Squibb, Incyte, and SecuraBio"},{"name":"Affimed, Imbrium Therapeutics L.P.\/Purdue, Janpix Ltd., Merck, Seattle Genetics, and Takeda"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Historic outcomes for patients with relapsed or refractory nodal-based T-cell lymphomas are poor, with survival generally measured in months in multiple reports from the late 20th and early 21st century. Until recently, salvage strategies have mostly been borrowed from other aggressive lymphomas. However, dedicated investigations into the pathogenesis of T-cell lymphomas have resulted in an outpouring of therapies that target these diseases in biologically rational strategies. In particular, an evolving appreciation of the multiple complex oncogenic pathways and epigenetic changes that underlie these diseases has led to numerous agents targeting these aberrancies. Moreover, large reports of salvage allogeneic stem cell transplants in T-cell lymphoma have now been published, showing that adaptive immunotherapy is a potentially curative strategy for patients with relapsed or refractory disease. This review highlights therapeutic advances for relapsed or refractory T-cell lymphomas, including cellular therapy and allogeneic stem cell transplant, and provides a framework for management.<\/jats:p>","DOI":"10.3390\/cancers15030589","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:06:14Z","timestamp":1674104774000},"page":"589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Therapeutic Advances in Relapsed and Refractory Peripheral T-Cell Lymphoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Robert","family":"Stuver","sequence":"first","affiliation":[{"name":"Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J.","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A report from the Clinical Advisory Committee","volume":"140","author":"Campo","year":"2022","journal-title":"Blood"},{"key":"ref_3","unstructured":"Howlander, N., Noone, A., Krapcho, M., Garshell, J., and Miller, D. (2014). Seer Cancer Statistics Review, 1975\u20132011."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1093\/annonc\/mdh392","article-title":"Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification","volume":"15","author":"Savage","year":"2004","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1182\/blood.V106.11.811.811","article-title":"International Peripheral T-Cell Lymphoma (PTCL) Clinical and Pathologic Review Project: Poor Outcome by Prognostic Indices and Lack of Efficacy with Anthracyclines","volume":"106","author":"Vose","year":"2005","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1002\/cncr.30416","article-title":"A prospective cohort study of patients with peripheral T-cell lymphoma in the United States","volume":"123","author":"Carson","year":"2016","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1200\/JCO.2012.44.7524","article-title":"Survival of Patients With Peripheral T-Cell Lymphoma After First Relapse or Progression: Spectrum of Disease and Rare Long-Term Survivors","volume":"31","author":"Mak","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/hon.2144","article-title":"Dismal outcome of t-cell lymphoma patients failing first-line treatment: Results of a population-based study from the Modena Cancer Registry","volume":"33","author":"Biasoli","year":"2014","journal-title":"Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.3324\/haematol.2017.186577","article-title":"The outcome of peripheral T-cell lymphoma patients failing first-line therapy: A report from the prospective, International T-Cell Project","volume":"103","author":"Bellei","year":"2018","journal-title":"Haematologica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000500666","article-title":"Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry","volume":"143","author":"Lansigan","year":"2019","journal-title":"Acta Haematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1200\/JCO.2014.59.2782","article-title":"Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study","volume":"33","author":"Horwitz","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1182\/blood-2017-05-780049","article-title":"Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma","volume":"130","author":"Pro","year":"2017","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1182\/blood.V87.1.284.284","article-title":"High Incidence of the t(2;5)(p23;q35) Translocation in Anaplastic Large Cell Lymphoma and Its Lack of Detection in Hodgkin\u2019s Disease. Comparison of Cytogenetic Analysis, Reverse Transcriptase-Polymerase Chain Reaction, and P-80 Immunostaining","volume":"87","author":"Lamant","year":"1996","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1200\/JCO.2010.29.9024","article-title":"Pralatrexate in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results From the Pivotal PROPEL Study","volume":"29","author":"Pro","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1756-8722-7-11","article-title":"Romidepsin for the treatment of relapsed\/refractory peripheral T-cell lymphoma: Pivotal study update demonstrates durable responses","volume":"7","author":"Coiffier","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1182\/blood.V106.11.2679.2679","article-title":"Second-Line Therapy with ICE Followed by High Dose Therapy and Autologous Stem Cell Transplantation for Relapsed\/Refractory Peripheral T-Cell Lymphomas: Minimal Benefit When Analyzed by Intent To Treat","volume":"106","author":"Horwitz","year":"2005","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1002\/cncr.25216","article-title":"Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin)\u00b1rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma","volume":"116","author":"Rigacci","year":"2010","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1182\/blood-2017-11-764357","article-title":"Novel insights into the pathogenesis of T-cell lymphomas","volume":"131","author":"Lim","year":"2018","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K Pathway in Human Disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1182\/blood-2017-08-802470","article-title":"Activity of the PI3K-\u03b4,\u03b3 inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma","volume":"131","author":"Horwitz","year":"2018","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1097\/01.HS9.0000847552.42271.7c","article-title":"Duvelisib in patients with relapsed\/refractory peripheral T-cell lymphoma from the phase 2 PRIMO trial: Updated expansion phase analysis","volume":"6","author":"Zinzani","year":"2022","journal-title":"Hemasphere"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Huen, A., Haverkos, B.M., Zain, J., Radhakrishnan, R., Lechowicz, M.J., Devata, S., Korman, N.J., Pinter-Brown, L., Oki, Y., and Barde, P.J. (2020). Phase I\/Ib Study of Tenalisib (RP6530), a Dual PI3K \u03b4\/\u03b3 Inhibitor in Patients with Relapsed\/Refractory T-Cell Lymphoma. Cancers, 12.","DOI":"10.3390\/cancers12082293"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1093\/annonc\/mdx289","article-title":"Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma","volume":"28","author":"Dreyling","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9395","DOI":"10.1182\/blood-2022-162127","article-title":"A Study of Linperlisib in the Treatment of Patients with Relapsed and\/or Refractory Peripheral T-Cell Lymphoma","volume":"140","author":"Qiu","year":"2022","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.annonc.2020.12.009","article-title":"Combination treatment of copanlisib and gemcitabine in relapsed\/refractory PTCL (COSMOS): An open-label phase I\/II trial","volume":"32","author":"Yhim","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_26","unstructured":"(2022, January 01). FDA Briefing Document Oncologic Drugs Advisory Committee Meeting Phosphatidylinositol 3-Kinase (PI3K) Inhibitors in Hematologic Malignancies, Available online: https:\/\/www.fda.gov\/media\/157762\/download."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1182\/blood-2019-125017","article-title":"Final Results of a Phase II Biomarker-Driven Study of Ruxolitinib in Relapsed and Refractory T-Cell Lymphoma","volume":"134","author":"Moskowitz","year":"2019","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/leu.2013.271","article-title":"Recurrent JAK1 and JAK3 somatic mutations in T-cell prolymphocytic leukemia","volume":"28","author":"Bellanger","year":"2013","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/bjh.13952","article-title":"Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia","volume":"173","author":"Bergmann","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1038\/leu.2013.104","article-title":"STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia","volume":"27","author":"Ohgami","year":"2013","journal-title":"Leukemia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/sj.leu.2404104","article-title":"A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma","volume":"20","author":"Pautas","year":"2006","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103775","DOI":"10.18632\/oncotarget.21790","article-title":"Fusion of the genes ataxin 2 like, ATXN2L, and Janus kinase 2, JAK2, in cutaneous CD4 positive T-cell lymphoma","volume":"8","author":"Panagopoulos","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1182\/blood-2018-01-830968","article-title":"Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract","volume":"131","author":"Sharma","year":"2018","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1182\/blood.2021012536","article-title":"Primary cytotoxic T-cell lymphomas harbor recurrent targetable alterations in the JAK-STAT pathway","volume":"138","author":"Lee","year":"2021","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"TPS3148","DOI":"10.1200\/JCO.2020.38.15_suppl.TPS3148","article-title":"A phase II open-label multicenter study to assess the efficacy and safety of AFM13 in patients with relapsed or refractory CD30-positive peripheral T-cell lymphoma or transformed mycosis fungoides: The REDIRECT study design and rationale","volume":"38","author":"Alexis","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/01.HS9.0000843940.96598.e2","article-title":"S262: The Cobalt-Lym Study of CTX130: A Phase 1 Dose Escalation Study of CD70-Targeted Allogeneic Crispr-CAS9\u2013Engineered Car T Cells in Patients with Relapsed\/Refractory (R\/R) T-Cell Malignan-Cies","volume":"6","author":"Iyer","year":"2022","journal-title":"Hemasphere"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7563","DOI":"10.1200\/JCO.2022.40.16_suppl.7563","article-title":"A phase I\/II study of golidocitinib, a selective JAK1 inhibitor, in refractory or relapsed peripheral T-cell lymphoma","volume":"40","author":"Kim","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1182\/blood-2021-152603","article-title":"Nanatinostat (Nstat) and Valganciclovir (VGCV) in Relapsed\/Refractory (R\/R) Epstein-Barr Virus-Positive (EBV +) Lymphomas: Final Results from the Phase 1b\/2 VT3996-201 Study","volume":"138","author":"Haverkos","year":"2021","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.clml.2019.03.022","article-title":"Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma","volume":"19","author":"Barta","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_40","first-page":"3847","article-title":"The Combination of Duvelisib and Romidepsin (DR) Is Highly Active Against Relapsed\/Refractory Peripheral T-Cell Lymphoma with Low Rates of Transaminitis: Final Results and Biomarker Analysis","volume":"138","author":"Horwitz","year":"2021","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1182\/blood-2021-145851","article-title":"Safety and Efficacy of Tenalisib Given in Combination with Romidepsin in Patients with Relapsed\/Refractory T-Cell Lymphoma: Final Results from a Phase I\/II Open Label Multi-Center Study","volume":"138","author":"Iyer","year":"2021","journal-title":"Blood"},{"key":"ref_42","first-page":"4076","article-title":"A Single Direct Intratumoral Injection of TTI-621 (SIRP\u03b1Fc) Induces Antitumor Activity in Patients with Relapsed\/Refractory Mycosis Fungoides and S\u00e9zary Syndrome: Preliminary Findings Employing an Immune Checkpoint Inhibitor Blocking the CD47 Do Not Eat Signal","volume":"130","author":"Querfeld","year":"2017","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1158\/1078-0432.CCR-20-3706","article-title":"Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies","volume":"27","author":"Ansell","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_44","first-page":"293","article-title":"Current Treatment of Peripheral T-cell Lymphoma","volume":"36","author":"Stuver","year":"2022","journal-title":"Oncology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ishitsuka, K., Izutsu, K., Maruyama, D., Makita, S., Jacobsen, E.D., Horwitz, S., Kusumoto, S., Allen, P., Porcu, P., and Imaizumi, Y. (2021). First in-human study of the EZH1 and EZH2 dual inhibitor valemetostat (DS-3201B) in patients with relapsed or refractory non-Hodgkin lymphoma. Hematol. Oncol., 39.","DOI":"10.1002\/hon.14_2879"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/leu.2008.77","article-title":"Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas","volume":"22","author":"Feldman","year":"2008","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1182\/blood-2019-123986","article-title":"A Phase 2 Study of the Dual SYK\/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability and Clinical Response in Relapsed\/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma","volume":"134","author":"Horwitz","year":"2019","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1182\/blood-2006-10-055145","article-title":"The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells","volume":"109","author":"Rickman","year":"2007","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1182\/blood-2013-10-531509","article-title":"A targeted mutational landscape of angioimmunoblastic T-cell lymphoma","volume":"123","author":"Odejide","year":"2014","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.3324\/haematol.2016.158428","article-title":"Integrative clinicopathological and molecular analyses of angioimmunoblastic T-cell lymphoma and other nodal lymphomas of follicular helper T-cell origin","volume":"102","author":"Dobay","year":"2017","journal-title":"Haematologica"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1182\/bloodadvances.2020002396","article-title":"T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed\/refractory peripheral T-cell lymphoma","volume":"4","author":"Ghione","year":"2020","journal-title":"Blood Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/ajh.26288","article-title":"Romidepsin and lenalidomide-based regimens have efficacy in relapsed\/refractory lymphoma: Combined analysis of two phase I studies with expansion cohorts","volume":"96","author":"Lunning","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1182\/blood.2020009004","article-title":"Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: A multicenter phase 2 study","volume":"137","author":"Falchi","year":"2021","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia","volume":"383","author":"Dinardo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1056\/NEJMoa2004444","article-title":"Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission","volume":"383","author":"Wei","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/leu.2011.342","article-title":"DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia","volume":"26","author":"Metzeler","year":"2011","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1182\/blood-2014-06-582809","article-title":"TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients","volume":"124","author":"Bejar","year":"2014","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1182\/blood-2018-04-840538","article-title":"Treatment with 5-azacytidine induces a sustained response in patients with angioimmunoblastic T-cell lymphoma","volume":"132","author":"Lemonnier","year":"2018","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1182\/blood-2022-156789","article-title":"Oral Azacytidine in Patients with Relapsed\/Refractory Angioimmunoblastic T-Cell Lymphoma: Final Analysis of the Oracle Phase III Study","volume":"140","author":"Dupuis","year":"2022","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.3109\/10428194.2014.968780","article-title":"Enhancer of zeste homolog 2 is widely expressed in T-cell neoplasms, is associated with high proliferation rate and correlates with MYC and pSTAT3 expression in a subset of cases","volume":"56","author":"Shi","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1101\/gad.186411.111","article-title":"A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia","volume":"26","author":"Simon","year":"2012","journal-title":"Genes Dev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Izutsu, K., Makita, S., Nosaka, K., Yoshimitsu, M., Utsunomiya, A., Kusumoto, S., Morishima, S., Tsukasaki, K., Kawamata, T., and Ono, T. (2022). An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia\/Lymphoma. Blood.","DOI":"10.1182\/blood.2022016862"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.1182\/bloodadvances.2020001966","article-title":"Enhancing antitumor immunity through checkpoint blockade as a therapeutic strategy in T-cell lymphomas","volume":"4","author":"Neuwelt","year":"2020","journal-title":"Blood Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1182\/blood-2009-04-216671","article-title":"B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders","volume":"114","author":"Wilcox","year":"2009","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/PAS.0b013e3181cc7e79","article-title":"PD-1 Expression in T-cell Lymphomas and Reactive Lymphoid Entities: Potential Overlap in Staining Patterns Between Lymphoma and Viral Lymphadenitis","volume":"34","author":"Krishnan","year":"2010","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nature24649","article-title":"PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis","volume":"552","author":"Wartewig","year":"2017","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1056\/NEJMc1803181","article-title":"Rapid Progression of Adult T-Cell Leukemia\u2013Lymphoma after PD-1 Inhibitor Therapy","volume":"378","author":"Ratner","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1182\/blood.2019002038","article-title":"Rapid progression of adult T-cell leukemia\/lymphoma as tumor-infiltrating Tregs after PD-1 blockade","volume":"134","author":"Rauch","year":"2019","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1056\/NEJMc1807852","article-title":"PD-1 Inhibitor Therapy in Adult T-Cell Leukemia\u2013Lymphoma","volume":"379","author":"Ishitsuka","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e004984","DOI":"10.1136\/jitc-2022-004984","article-title":"Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: Modest activity and cases of hyperprogression","volume":"10","author":"Bennani","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2020-143252","article-title":"A Phase II Study of Pembrolizumab in Combination with Romidepsin Demonstrates Durable Responses in Relapsed or Refractory T-Cell Lymphoma (TCL)","volume":"136","author":"Iyer","year":"2020","journal-title":"Blood"},{"key":"ref_72","unstructured":"Zinzani, P., Zhang, Q., Gritti, G., Cao, J., Liberati, A.M., Hu, J., Huang, H., Savage, K.J., Kwong, Y.L., and Porcu, P. (2020). Tislelizumab (BGB-A317) for Relapsed\/Refractory Peripheral T-Cell Lymphoma, EHA Library."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1182\/blood-2016-12-756841","article-title":"PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK\/T-cell lymphoma failing l-asparaginase","volume":"129","author":"Kwong","year":"2017","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00277-017-3127-2","article-title":"PD1 blockade with low-dose nivolumab in NK\/T cell lymphoma failing l-asparaginase: Efficacy and safety","volume":"97","author":"Chan","year":"2017","journal-title":"Ann. Hematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1200\/JCO.19.01056","article-title":"Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and S\u00e9zary Syndrome: A Multicenter Phase II Study","volume":"38","author":"Khodadoust","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1182\/bloodadvances.2020002371","article-title":"Pembrolizumab in mycosis fungoides with PD-L1 structural variants","volume":"5","author":"Beygi","year":"2021","journal-title":"Blood Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.coi.2012.01.010","article-title":"The CD47\u2013SIRP\u03b1 pathway in cancer immune evasion and potential therapeutic implications","volume":"24","author":"Chao","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMoa1807315","article-title":"CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin\u2019s Lymphoma","volume":"379","author":"Advani","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3109\/10428194.2011.573031","article-title":"Lenalidomide monotherapy for relapsed\/refractory peripheral T-cell lymphoma not otherwise specified","volume":"52","author":"Zinzani","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1016\/j.ejca.2013.04.029","article-title":"A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid\u00ae) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: The EXPECT trial","volume":"49","author":"Morschhauser","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/cncr.29103","article-title":"Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma","volume":"121","author":"Toumishey","year":"2014","journal-title":"Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1200\/JCO.2011.37.3472","article-title":"Defucosylated Anti-CCR4 Monoclonal Antibody (KW-0761) for Relapsed Adult T-Cell Leukemia-Lymphoma: A Multicenter Phase II Study","volume":"30","author":"Ishida","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e407","DOI":"10.3324\/haematol.2016.146977","article-title":"European phase II study of mogamulizumab, an anti-CCR4 monoclonal antibody, in relapsed\/refractory peripheral T-cell lymphoma","volume":"101","author":"Zinzani","year":"2016","journal-title":"Haematologica"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"993","DOI":"10.3324\/haematol.2018.205096","article-title":"Mogamulizumab versus investigator\u2019s choice of chemotherapy regimen in relapsed\/refractory adult T-cell leukemia\/lymphoma","volume":"104","author":"Phillips","year":"2018","journal-title":"Haematologica"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/ejh.13220","article-title":"Safety and effectiveness of mogamulizumab in relapsed or refractory adult T-cell leukemia-lymphoma","volume":"102","author":"Ishitsuka","year":"2019","journal-title":"Eur. J. Haematol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1182\/blood-2021-154142","article-title":"Early Signals of Anti-Tumor Efficacy and Safety with Autologous CD5.CAR T-Cells in Patients with Refractory\/Relapsed T-Cell Lymphoma","volume":"138","author":"Rouce","year":"2021","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1182\/blood-2021-146100","article-title":"Safety and Efficacy Profile of Autologous CD30.CAR-T-Cell Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (CHARIOT Trial)","volume":"138","author":"Ahmed","year":"2021","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1172\/JCI94306","article-title":"Clinical and immunological responses after CD30-specific chimeric antigen receptor\u2013redirected lymphocytes","volume":"127","author":"Ramos","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1182\/blood-2021-148102","article-title":"CD30-Directed CAR-T Cells Co-Expressing CCR4 in Relapsed\/Refractory Hodgkin Lymphoma and CD30+ Cutaneous T Cell Lymphoma","volume":"138","author":"Grover","year":"2021","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E319","DOI":"10.1002\/ajh.25967","article-title":"Phase two study of crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma relapsed\/refractory to chemotherapy","volume":"95","author":"Bossi","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1111\/cas.14671","article-title":"Alectinib for relapsed or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: An open-label phase II trial","volume":"111","author":"Fukano","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"106164","DOI":"10.1016\/j.leukres.2019.05.014","article-title":"Central nervous system relapse of systemic ALK-rearranged anaplastic large cell lymphoma treated with alectinib","volume":"83","author":"Tomlinson","year":"2019","journal-title":"Leuk. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e247","DOI":"10.1016\/j.clml.2019.03.001","article-title":"Treatment of Refractory ALK Rearranged Anaplastic Large Cell Lymphoma With Alectinib","volume":"19","author":"Reed","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1182\/bloodadvances.2021005899","article-title":"Outcome of allogeneic transplantation for mature T-cell lymphomas: Impact of donor source and disease characteristics","volume":"6","author":"Hamadani","year":"2022","journal-title":"Blood Adv."},{"key":"ref_95","first-page":"35","article-title":"Successful Treatment of Mature T-Cell Lymphoma with Allogeneic Stem Cell Transplantation: The Largest Multicenter Retrospective Analysis","volume":"136","author":"Kommalapati","year":"2020","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1056\/NEJM199512073332305","article-title":"Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin\u2019s Lymphoma","volume":"333","author":"Philip","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/annonc\/mdg459","article-title":"High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: The GEL-TAMO experience","volume":"14","author":"Caballero","year":"2003","journal-title":"Ann. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1046\/j.1365-2141.2003.04203.x","article-title":"Autologous stem cell transplant for relapsed and refractory peripheral T-cell lymphoma: Variable outcome according to pathological subtype","volume":"120","author":"Song","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1365-2141.2006.06164.x","article-title":"Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma","volume":"134","author":"KewalRamani","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.bbmt.2008.04.004","article-title":"Long-Term Results Of Autologous Hematopoietic Cell Transplantation For Peripheral T Cell Lymphoma: The Stanford Experience","volume":"14","author":"Chen","year":"2008","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1200\/JCO.2012.46.0188","article-title":"Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma","volume":"31","author":"Smith","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.bbmt.2015.01.013","article-title":"Comparison of Survival in Patients with T Cell Lymphoma after Autologous and Allogeneic Stem Cell Transplantation as a Frontline Strategy or in Relapsed Disease","volume":"21","author":"Beitinjaneh","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_103","first-page":"796","article-title":"Autologous hematopoietic stem cell transplantation for relapsed\/refractory systemic anaplastic large cell lymphoma. A retrospective analysis of the lymphoma working party (LWP) of the EBMT","volume":"55","author":"Boumendil","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/s41375-022-01545-w","article-title":"Autologous or allogeneic hematopoietic cell transplantation for relapsed or refractory PTCL-NOS or AITL","volume":"36","author":"Kameda","year":"2022","journal-title":"Leukemia"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"285","DOI":"10.6004\/jnccn.2022.0015","article-title":"T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Horwitz","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/bjh.17951","article-title":"Guidelines for the management of mature T- and natural killer-cell lymphomas (excluding cutaneous T-cell lymphoma): A British Society for Haematology Guideline","volume":"196","author":"Fox","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1200\/JCO.2012.48.3883","article-title":"Strategies for Relapsed Peripheral T-Cell Lymphoma: The Tail That Wags the Curve","volume":"31","author":"Lunning","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1200\/JCO.2015.66.3476","article-title":"Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis","volume":"34","author":"Ghosh","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1182\/blood-2015-09-671834","article-title":"Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors","volume":"127","author":"Kanate","year":"2016","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/ajh.25463","article-title":"Single agents vs combination chemotherapy in relapsed and refractory peripheral T-cell lymphoma: Results from the comprehensive oncology measures for peripheral T-cell lymphoma treatment (COMPLETE) registry","volume":"94","author":"Stuver","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/hon.2705","article-title":"Survival benefit in patients with peripheral T-cell lymphomas after treatments with novel therapies and clinical trials","volume":"38","author":"Ma","year":"2020","journal-title":"Hematol. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1182\/blood.2021013379","article-title":"A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK\/STAT targeting in T-cell lymphomas","volume":"138","author":"Moskowitz","year":"2021","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/3\/589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:09:13Z","timestamp":1760119753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/3\/589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":112,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["cancers15030589"],"URL":"https:\/\/doi.org\/10.3390\/cancers15030589","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}