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Der Hautarzt; Zeitschrift Fur... Sep 2017Primary cutaneous lymphomas can be diagnosed when the clinical symptoms, histology, immunohistology and molecular biological changes are characteristic of primary... (Review)
Review
Primary cutaneous lymphomas can be diagnosed when the clinical symptoms, histology, immunohistology and molecular biological changes are characteristic of primary cutaneous T or B‑cell lymphomas; however, in many cases not all of the changes are typical of a primary cutaneous lymphoma especially in the early stages; therefore, the diagnosis of a primary cutaneous lymphoma can be a challenge. This is especially true for the Sézary syndrome, which can initially prove to be difficult to differentiate from reactive erythroderma; therefore, the main focus of this review is the diagnostics of Sézary syndrome. The review also summarizes the clinical heterogeneity and describes the classical histological and immunohistochemical changes for the diagnosis of Sézary syndrome. Recent data from different multicenter, international studies by the cutaneous lymphoma task force of the European Organisation for Research and Treatment of Cancer (EORTC) on dermatological alterations of the skin and the detection of Sézary cells in blood are addressed. The detection of Sézary cells in the blood still remains a challenge despite improved molecular boiological and cytogenetic characterization of tumor cells. The latest studies of the EORTC group particularly identified CD158k, MYC, MNT, DNM, TWIST1, EPHA4 and PLS3 as valuable markers for the differentiation of reactive erythroderma but which are not yet part of the standard diagnostics of Sézary syndrome. Further studies are required to see if these markers can be used in the routine clinical application.
Topics: Biomarkers, Tumor; Biopsy; Diagnosis, Differential; Diagnostic Imaging; Humans; Immunohistochemistry; Lymphoma, B-Cell; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin; Skin Neoplasms
PubMed: 28779267
DOI: 10.1007/s00105-017-4020-6 -
Frontiers in Immunology 2023Mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T cell lymphoma (CTCL) that pose significant challenges in their clinical management,... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T cell lymphoma (CTCL) that pose significant challenges in their clinical management, particularly in refractory and advanced-stage disease. With the emergence of novel therapeutic modalities however, there are increasing opportunities to exploit the current understanding of pathophysiologic mechanisms of MF/SS for treatment. This review summarizes recent advances in the treatment of MF/SS, with a focus on monoclonal antibodies, immunotherapies, and Janus kinase (JAK) inhibitors, including ongoing clinical trials.
Topics: Humans; Sezary Syndrome; Antibodies, Monoclonal; Janus Kinase Inhibitors; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Immunotherapy
PubMed: 38022633
DOI: 10.3389/fimmu.2023.1291259 -
Chinese Clinical Oncology Feb 2019Mycosis fungoides (MF) and Sézary syndrome (SS) are two well-characterized skin limited and leukemic subtypes of cutaneous T-cell lymphoma (CTCL), respectively.... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are two well-characterized skin limited and leukemic subtypes of cutaneous T-cell lymphoma (CTCL), respectively. Progressive global immune dysfunction and a multitude of specific immunological abnormalities have long been recognized as features of MF and SS. Therefore, a variety of immune-based therapies have been explored and used in the clinic for decades in the attempt to restore the immune imbalance in these malignancies. With recent advances in the development of novel immunotherapies in cancer treatment, new treatment modalities have emerged to complement the existing repertoire. Herein, we provide a comprehensive review of immune evasive mechanisms in MF/SS and summarize the established and emerging immunotherapies for these malignancies. We explain the underlying mechanisms of these immune-based therapies and derive recommendation from results of major clinical trials.
Topics: Humans; Immunotherapy; Mycosis Fungoides; Sezary Syndrome
PubMed: 30691274
DOI: 10.21037/cco.2019.01.01 -
Seminars in Diagnostic Pathology Jan 2017Mycosis Fungoides (MF) and Sézary Syndrome (SS) are clonal proliferations of mature T-cells manifesting as lymphoproliferative disorders in which the neoplastic cells... (Review)
Review
Mycosis Fungoides (MF) and Sézary Syndrome (SS) are clonal proliferations of mature T-cells manifesting as lymphoproliferative disorders in which the neoplastic cells show a strong propensity for skin-homing. While the predominant site of presentation in MF is the skin, the peripheral blood carries a significant tumor burden in Sézary Syndrome such that it resembles a "leukemic" disease. While the genetic basis of these diseases has been studied using different approaches in the previous years, recent genome-wide studies employing massively parallel sequencing techniques now offer new insights into the molecular pathogenesis of these diseases. In this chapter, we discuss the recent findings elucidating the genomic landscape of MF and SS. The pathways targeted by mutational alterations are discussed and a model for understanding the pathogenesis of these diseases is proposed. It is anticipated that prognostic stratification and therapeutic targeting based on mutational signatures will be achieved in the near future based on the improved understanding of the molecular pathogenesis of these diseases.
Topics: Humans; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 28024703
DOI: 10.1053/j.semdp.2016.11.002 -
Expert Review of Anticancer Therapy Sep 2021The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments... (Review)
Review
INTRODUCTION
The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches.
AREAS COVERED
In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors.
EXPERT OPINION
Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future.
Topics: Disease Progression; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 33554707
DOI: 10.1080/14737140.2021.1882859 -
Bone Marrow Transplantation Jun 2021
Topics: Hematopoietic Stem Cell Transplantation; Humans; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 33526916
DOI: 10.1038/s41409-020-01150-4 -
Frontiers in Immunology 2023Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at... (Review)
Review
Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials.
Topics: Humans; Sezary Syndrome; Quality of Life; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Mycoses
PubMed: 37868986
DOI: 10.3389/fimmu.2023.1284045 -
Cells Nov 2023In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in... (Review)
Review
In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.
Topics: Humans; Skin Neoplasms; Mycosis Fungoides; Brentuximab Vedotin; Sezary Syndrome; Antineoplastic Agents; Antibodies, Monoclonal
PubMed: 37998391
DOI: 10.3390/cells12222656 -
Der Hautarzt; Zeitschrift Fur... Sep 2017Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification.... (Review)
Review
Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification. There is no curative therapy for CTCL yet, so that treatment currently aims at improving symptoms and quality of life as well as reducing relapse rates. The treatment has to be stage-adapted. Therapeutic options comprise skin-directed as well as systemic treatment. In early stages, phototherapy and local steroids are the first-line therapeutic options. For the therapy of higher stages, interferon alpha and the RXR-specific retinoid bexarotene are used as first-line medications. Second-line treatment comprises monochemotherapy with agents like gemcitabine or liposomal doxorubicine. Nevertheless, the high relapse rates in higher stages make novel alternative treatment options necessary. As future therapy, especially the fusion protein brentuximab-vedotin directed against CD30 shows promising potential in clinical studies.
Topics: Adrenal Cortex Hormones; Bexarotene; Brentuximab Vedotin; Deoxycytidine; Doxorubicin; Humans; Immunoconjugates; Interferon-alpha; Mycosis Fungoides; Neoplasm Recurrence, Local; Neoplasm Staging; PUVA Therapy; Phototherapy; Polyethylene Glycols; Sezary Syndrome; Skin Neoplasms; World Health Organization; Gemcitabine
PubMed: 28770285
DOI: 10.1007/s00105-017-4021-5 -
Dermatology (Basel, Switzerland) 2021Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is...
BACKGROUND
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management.
METHODS
A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies.
RESULTS
Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia.
CONCLUSIONS
This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.
Topics: Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Canada; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Retrospective Studies; Sezary Syndrome; Skin Neoplasms; Treatment Outcome; Young Adult
PubMed: 33429396
DOI: 10.1159/000512484