{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T01:51:58Z","timestamp":1756000318791,"version":"3.30.2"},"reference-count":44,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The cutaneous T-cell lymphomas (CTCLs) comprise a diverse set of diseases with equally diverse presentations ranging from asymptomatic solitary lesions to highly aggressive diseases with propensity for visceral spread. The more aggressive CTCLs, which herein we consider as certain cases of advanced-stage mycosis fungoides\/S\u00e9zary syndrome (MF\/SS), primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETCL), and primary cutaneous gamma delta T-cell lymphoma (PCGDTCL), require systemic therapy. Over the last 5 years, treatment options for MF\/SS have expanded with biological insights leading to new therapeutic options and increasingly unique management strategies. An enhanced appreciation of the compartmental efficacy of these agents (skin, blood, lymph nodes, visceral organs) is incorporated in current management strategies in MF\/SS. In addition, approaches that combine modalities in attempts to increase depth and durability of responses across multiple compartments are being trialed. In contrast to MF\/SS, PCAETCL and PCGDTCL remain diseases with few prospective studies to guide treatment. However, recent genomic insights on these diseases, such as the presence of JAK2 fusions in PCAETCL and cell of origin findings in PCGDTCL, have created options for new biomarker-driven strategies.<\/jats:p>","DOI":"10.1182\/hematology.2024000529","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T15:05:46Z","timestamp":1733497546000},"page":"62-68","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["Through thick and thin: confronting the aggressive cutaneous T-cell lymphomas"],"prefix":"10.1182","volume":"2024","author":[{"given":"Robert","family":"Stuver","sequence":"first","affiliation":[{"name":"1 Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M.","family":"Horwitz","sequence":"additional","affiliation":[{"name":"1 Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"2 Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"issue":"7","key":"2024121115464659700_hem2024000529C1","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"},{"issue":"10","key":"2024121115464659700_hem2024000529C2","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1093\/annonc\/mdx352","article-title":"Global patterns of care in advanced stage mycosis fungoides\/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium","volume":"28","author":"Quaglino","year":"2017","journal-title":"Ann Oncol"},{"issue":"31","key":"2024121115464659700_hem2024000529C3","doi-asserted-by":"crossref","first-page":"4730","DOI":"10.1200\/JCO.2009.27.7665","article-title":"Survival outcomes and prognostic factors in mycosis fungoides\/S\u00e9zary syndrome: validation of the revised International Society for Cutaneous Lymphomas\/European Organisation for Research and Treatment of Cancer staging proposal","volume":"28","author":"Agar","year":"2010","journal-title":"J Clin Oncol"},{"issue":"11","key":"2024121115464659700_hem2024000529C4","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41408-020-00380-5","article-title":"Targeted genomic analysis of cutaneous T cell lymphomas identifies a subset with aggressive clinicopathological features","volume":"10","author":"Argyropoulos","year":"2020","journal-title":"Blood Cancer J"},{"issue":"9","key":"2024121115464659700_hem2024000529C5","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/ng.3356","article-title":"Genomic landscape of cutaneous T cell lymphoma","volume":"47","author":"Choi","year":"2015","journal-title":"Nat Genet"},{"issue":"7","key":"2024121115464659700_hem2024000529C6","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1182\/blood.2020008241","article-title":"Integrating novel agents into the treatment of advanced mycosis fungoides and S\u00e9zary syndrome","volume":"141","author":"Khodadoust","year":"2023","journal-title":"Blood"},{"issue":"10094","key":"2024121115464659700_hem2024000529C7","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0140-6736(17)31266-7","article-title":"Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial","volume":"390","author":"Prince","year":"2017","journal-title":"Lancet"},{"issue":"9","key":"2024121115464659700_hem2024000529C8","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/S1470-2045(18)30379-6","article-title":"Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial","volume":"19","author":"Kim","year":"2018","journal-title":"Lancet Oncol"},{"issue":"Suppl 1","key":"2024121115464659700_hem2024000529C9","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1182\/blood-2020-141379","article-title":"Patient characteristics of long-term responders to mogamulizumab: results from the MAVORIC Study","volume":"136","author":"Kim","year":"2020","journal-title":"Blood"},{"issue":"7","key":"2024121115464659700_hem2024000529C10","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/eji.202049043","article-title":"CCR4 in cutaneous T-cell lymphoma: therapeutic targeting of a pathogenic driver","volume":"51","author":"Nicolay","year":"2021","journal-title":"Eur J Immunol"},{"issue":"6","key":"2024121115464659700_hem2024000529C11","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1001\/jamadermatol.2021.0877","article-title":"Clinical characterization of mogamulizumab-associated rash during treatment of mycosis fungoides or S\u00e9zary syndrome","volume":"157","author":"Hirotsu","year":"2021","journal-title":"JAMA Dermatol"},{"issue":"Suppl 1","key":"2024121115464659700_hem2024000529C12","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1182\/blood-2022-166887","article-title":"Mogamulizumab-associated rash (MAR) correlates with longer progression free survival in cutaneous T cell lymphoma (CTCL)","volume":"140","author":"Hu","year":"2022","journal-title":"Blood"},{"issue":"14","key":"2024121115464659700_hem2024000529C13","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1158\/1078-0432.CCR-16-3185","article-title":"Usefulness of KIR3DL2 to diagnose, follow-up, and manage the treatment of patients with S\u00e9zary syndrome","volume":"23","author":"Hurabielle","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"8","key":"2024121115464659700_hem2024000529C14","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/S1470-2045(19)30320-1","article-title":"IPH4102, a first-in-class anti-KIR3DL2 monoclonal antibody, in patients with relapsed or refractory cutaneous T-cell lymphoma: an international, first-in-human, open-label, phase 1 trial","volume":"20","author":"Bagot","year":"2019","journal-title":"Lancet Oncol"},{"issue":"Suppl 1","key":"2024121115464659700_hem2024000529C15","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1182\/blood-2022-160239","article-title":"Lacutamab in patients with advanced Sezary syndrome: results from an interim analysis of the TELLOMAK phase 2 trial","volume":"140","author":"Bagot","year":"2022","journal-title":"Blood"},{"issue":"S2","key":"2024121115464659700_hem2024000529C16","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/hon.3163_127","article-title":"Lacutamab in patients with advanced mycosis fungoides (MF): efficacy results according to updated lymph node (LN) classification in the TELLOMAK study","volume":"41","author":"Kim","year":"2023","journal-title":"Hematol Oncol"},{"issue":"1","key":"2024121115464659700_hem2024000529C17","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"},{"issue":"1","key":"2024121115464659700_hem2024000529C18","doi-asserted-by":"crossref","first-page":"6726","DOI":"10.1038\/s41467-021-26974-6","article-title":"Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma","volume":"12","author":"Phillips","year":"2021","journal-title":"Nat Commun"},{"issue":"2","key":"2024121115464659700_hem2024000529C19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jaad.2014.10.014","article-title":"Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase-II clinical trials","volume":"72","author":"Hoppe","year":"2015","journal-title":"J Am Acad Dermatol"},{"issue":"3","key":"2024121115464659700_hem2024000529C20","doi-asserted-by":"crossref","first-page":"100629","DOI":"10.1016\/j.adro.2020.11.014","article-title":"Low-dose total skin electron beam therapy combined with mogamulizumab for refractory mycosis fungoides and S\u00e9zary syndrome","volume":"6","author":"Fong","year":"2021","journal-title":"Adv Radiat Oncol"},{"issue":"3","key":"2024121115464659700_hem2024000529C21","first-page":"279","article-title":"Low-dose total skin electron beam therapy plus oral bexarotene maintenance therapy for cutaneous T-cell lymphoma","volume":"20","author":"Elsayad","year":"2022","journal-title":"J Dtsch Dermatol Ges"},{"issue":"Suppl 1","key":"2024121115464659700_hem2024000529C22","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1182\/blood-2023-184898","article-title":"Reduced dose brentuximab vedotin for mycosis fungoides appears to prolong response duration by balancing efficacy and tolerability","volume":"142","author":"Munayirji","year":"2023","journal-title":"Blood"},{"issue":"18","key":"2024121115464659700_hem2024000529C23","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1182\/bloodadvances.2020001627","article-title":"Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma","volume":"4","author":"Weng","year":"2020","journal-title":"Blood Adv"},{"issue":"4","key":"2024121115464659700_hem2024000529C24","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/his.12371","article-title":"Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop","volume":"67","author":"Robson","year":"2015","journal-title":"Histopathology"},{"issue":"5","key":"2024121115464659700_hem2024000529C25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/modpathol.2016.240","article-title":"Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas","volume":"30","author":"Guitart","year":"2017","journal-title":"Mod Pathol"},{"issue":"23","key":"2024121115464659700_hem2024000529C26","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"},{"issue":"5","key":"2024121115464659700_hem2024000529C27","first-page":"e15132","article-title":"Long-term remission after matched sibling donor hematopoietic cell transplantation in a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma","volume":"13","author":"Gesiotto","year":"2021","journal-title":"Cureus"},{"issue":"3","key":"2024121115464659700_hem2024000529C28","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jdcr.2017.02.004","article-title":"Complete durable remission of a fulminant primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma after autologous and allogeneic hematopoietic stem cell transplantation","volume":"3","author":"Plachouri","year":"2017","journal-title":"JAAD Case Rep"},{"issue":"1","key":"2024121115464659700_hem2024000529C29","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1016\/j.clml.2017.11.004","article-title":"Transplantation in the treatment of primary cutaneous aggressive epidermotropic cytotoxic CD8-positive T-cell lymphoma","volume":"18","author":"Cyrenne","year":"2018","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"3","key":"2024121115464659700_hem2024000529C30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/10428194.2023.2287965","article-title":"Gemcitabine and liposomal doxorubicin (GemDox) for the treatment of relapsed and refractory T-cell lymphomas","volume":"65","author":"Braunstein","year":"2024","journal-title":"Leuk Lymphoma"},{"issue":"3","key":"2024121115464659700_hem2024000529C31","doi-asserted-by":"crossref","first-page":"702","DOI":"10.3324\/haematol.2020.274506","article-title":"Deregulation of JAK2 signaling underlies primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma","volume":"107","author":"Bastidas Torres","year":"2022","journal-title":"Haematologica"},{"issue":"26","key":"2024121115464659700_hem2024000529C32","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"},{"issue":"9","key":"2024121115464659700_hem2024000529C33","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1182\/blood-2002-05-1597","article-title":"Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma","volume":"101","author":"Toro","year":"2003","journal-title":"Blood"},{"issue":"2","key":"2024121115464659700_hem2024000529C34","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1182\/blood-2007-04-087288","article-title":"Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases","volume":"111","author":"Willemze","year":"2008","journal-title":"Blood"},{"issue":"1","key":"2024121115464659700_hem2024000529C35","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1038\/s41467-020-15572-7","article-title":"Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas","volume":"11","author":"Daniels","year":"2020","journal-title":"Nat Commun"},{"issue":"11","key":"2024121115464659700_hem2024000529C36","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1097\/PAS.0b013e31826a5038","article-title":"Cutaneous \u03b3\u03b4 T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas","volume":"36","author":"Guitart","year":"2012","journal-title":"Am J Surg Pathol"},{"issue":"6","key":"2024121115464659700_hem2024000529C37","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.jaad.2015.01.003","article-title":"Hematopoietic stem cell transplantation for primary cutaneous \u03b3\u03b4 T-cell lymphoma and refractory subcutaneous panniculitis-like T-cell lymphoma","volume":"72","author":"Gibson","year":"2015","journal-title":"J Am Acad Dermatol"},{"issue":"Suppl_1","key":"2024121115464659700_hem2024000529C38","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1182\/blood-2019-130223","article-title":"Characteristics, treatment patterns, and outcomes in primary cutaneous gamma delta T cell lymphoma (PCGDTCL): a real world multi-institutional analysis of a rare malignancy","volume":"134","author":"David","year":"2019","journal-title":"Blood"},{"issue":"6025","key":"2024121115464659700_hem2024000529C39","article-title":"Activating mutations of STAT5B and STAT3 in lymphomas derived from \u03b3\u03b4-T or NK cells","volume":"6","author":"K\u00fc\u00e7\u00fck","year":"2015","journal-title":"Nat Commun"},{"issue":"Suppl 1","key":"2024121115464659700_hem2024000529C40","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1182\/blood-2022-166916","article-title":"Efficacy and safety of E7777 (improved purity denileukin diftitox [ONTAK]) in patients with relapsed or refractory cutaneous T-cell lymphomas: results from pivotal Study 302","volume":"140","author":"Foss","year":"2022","journal-title":"Blood"},{"issue":"16","key":"2024121115464659700_hem2024000529C41","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1182\/bloodadvances.2022009575","article-title":"Treating relapsed\/refractory mature T- and NK-cell neoplasms with tislelizumab: a multicenter open-label phase 2 study","volume":"7","author":"Bachy","year":"2023","journal-title":"Blood Adv"},{"key":"2024121115464659700_hem2024000529C42","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/01.HS9.0000843940.96598.e2","article-title":"The COBALT-LYM study of CTX-130: a phase 1 dose escalation study of CD70-targeted allogeneic CRISPR-CAS9- engineered CAR T cells in patients with relapsed\/refractory (R\/R) T-cell malignancies","volume":"6","author":"Iyer","year":"2022","journal-title":"HemaSphere"},{"issue":"13","key":"2024121115464659700_hem2024000529C43","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1182\/blood.2023022204","article-title":"Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed\/refractory mature T-cell lymphomas","volume":"143","author":"Hill","year":"2024","journal-title":"Blood"},{"issue":"Suppl 1","key":"2024121115464659700_hem2024000529C44","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1182\/blood-2023-172980","article-title":"Innate cell engager (ICE\u00ae) AFM13 combined with preactivated and expanded (P+E) cord blood (CB)-derived natural killer (NK) cells for patients with refractory CD30-positive lymphomas: final results","volume":"142","author":"Nieto","year":"2023","journal-title":"Blood"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2024\/1\/62\/2346397\/62stuver.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2024\/1\/62\/2346397\/62stuver.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T20:13:36Z","timestamp":1733948016000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2024\/1\/62\/526193\/Through-thick-and-thin-confronting-the-aggressive"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12,6]]},"published-print":{"date-parts":[[2024,12,6]]}},"URL":"https:\/\/doi.org\/10.1182\/hematology.2024000529","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"type":"print","value":"1520-4391"},{"type":"electronic","value":"1520-4383"}],"subject":[],"published-other":{"date-parts":[[2024,12,6]]},"published":{"date-parts":[[2024,12,6]]}}}