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European Journal of Cancer (Oxford,... Dec 2023On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated... (Review)
Review
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
Topics: Humans; Mycosis Fungoides; Sezary Syndrome; Consensus; Quality of Life; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Immunologic Factors
PubMed: 37890355
DOI: 10.1016/j.ejca.2023.113343 -
CNS Oncology Dec 2023Cutaneous T-cell lymphoma (CTCL) is a rare hematologic malignancy that traditionally presents with cutaneous lesions, though metastases are not uncommon in progressive... (Review)
Review
Cutaneous T-cell lymphoma (CTCL) is a rare hematologic malignancy that traditionally presents with cutaneous lesions, though metastases are not uncommon in progressive disease. We describe four cases of CTCL with central nervous system (CNS) involvement, detailing the history, pathological characteristics, treatment response, and progression. Median time from initial diagnosis to CNS metastasis was ∼5.4 years (range 3.4-15.5 years) and survival after metastasis was ∼160 days (range 19 days-4.4 years). No patients achieved long-term (>5 years) survival, though some displayed varying degrees of remission following CNS-directed therapy. We conclude that clinicians must be attentive to the development of CNS metastases in patients with CTCL. The growing body of literature on such cases will inform evolving therapeutic guidelines on this rare CTCL complication.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Neoplasms, Second Primary; Skin Neoplasms
PubMed: 37877303
DOI: 10.2217/cns-2023-0014 -
JAAD Case Reports Nov 2023
PubMed: 37877094
DOI: 10.1016/j.jdcr.2023.08.044 -
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 Sep 2023Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are...
Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with Sézary syndrome (SS), a leukemic form of CTCL, was examined for the new fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and/or knockout assays were conducted in two CTCL cell lines (MJ cells and HH cells) by RNA interference and/or CRISPR/Cas9 gene editing. SS patients expressed heterogeneous levels of a new fusion transcript. Patients with high-level expression of showed poorer 5-year survival (n = 19, 42.1%) than patients with low-level expression (n = 14, 78.6%). CTCL cells transduced with specific shRNAs or sgRNAs had decreased new fusion transcript expression, reduced cell proliferation, and decreased colony formation. In NSG xenograft mice, smaller tumor sizes were observed in MJ cells transduced with specific shRNAs than cells transduced with controls. Our results suggest that the newly identified fusion transcript confers an oncogenic event in CTCL.
Topics: Animals; Humans; Mice; Janus Kinase 3; Lymphoma, T-Cell, Cutaneous; RNA, Guide, CRISPR-Cas Systems; RNA, Small Interfering; Sezary Syndrome; Skin Neoplasms; Oncogene Proteins, Fusion
PubMed: 37830594
DOI: 10.3390/cells12192381 -
Indian Journal of Dermatology 2023Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic...
Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD). While recent reports have described cases of new-onset mycosis fungoides (MF) following treatment with dupilumab for AD, to our knowledge only one patient has been delineated with the progression to SS. We present an additional case of a patient who was diagnosed with SS following treatment with dupilumab for adult-onset AD and asthma. We examine SS as a possible side effect of dupilumab while also discussing management and theories to explain this phenomenon.
PubMed: 37822402
DOI: 10.4103/ijd.ijd_580_22 -
Cureus Sep 2023Erythroderma is a general term used to describe severe, intense skin inflammation. The condition is also known as exfoliative dermatitis when it is associated with...
Erythroderma is a general term used to describe severe, intense skin inflammation. The condition is also known as exfoliative dermatitis when it is associated with exfoliation. Erythroderma has many causes, such as adverse drug eruption, dermatitis, psoriasis, pityriasis rubra pilaris, immunobullous disease, cutaneous T-cell lymphoma (Sézary syndrome), underlying systemic malignancy, graft versus host disease, and HIV infection. Many medications can cause erythroderma, including antibiotics, antiepileptics, angiotensin-converting enzyme (ACE) inhibitors, and sulfonamides. Here, we report a rare case of erythroderma secondary to gliclazide, an oral antidiabetic. This presentation is rare, as we found only one case report of gliclazide causing erythroderma in the literature. Erythroderma is considered a medical emergency requiring immediate diagnosis and prompt management; therefore, early intervention should start on suspicion without waiting for dermatologist confirmation, as this will significantly reduce the mortality and morbidity of this potentially life-threatening emergency.
PubMed: 37766779
DOI: 10.7759/cureus.45965 -
Cells Sep 2023Extracorporeal photopheresis (ECP) is an FDA-approved immunotherapy for cutaneous T-cell lymphoma, which can provide a complete response in some patients. However, it is... (Review)
Review
Extracorporeal photopheresis (ECP) is an FDA-approved immunotherapy for cutaneous T-cell lymphoma, which can provide a complete response in some patients. However, it is still being determined who will respond well, and predictive biomarkers are urgently needed to target patients for timely treatment and to monitor their response over time. The aim of this review is to analyze the current state of the diagnostic, prognostic, and disease state-monitoring biomarkers of ECP, and outline the future direction of the ECP biomarker discovery. Specifically, we focus on biomarkers of response to ECP in mycosis fungoides and Sézary syndrome. The review summarizes the current knowledge of ECP biomarkers, including their limitations and potential applications, and identifies key challenges in ECP biomarker discovery. In addition, we discuss emerging technologies that could revolutionize ECP biomarker discovery and accelerate the translation of biomarker research into clinical practice. This review will interest researchers and clinicians seeking to optimize ECP therapy for cutaneous T-cell lymphoma.
Topics: Humans; Sezary Syndrome; Photopheresis; Skin Neoplasms; Treatment Outcome; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Biomarkers
PubMed: 37759543
DOI: 10.3390/cells12182321 -
Disease Models & Mechanisms Oct 2023Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal...
Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, an immunodeficient knock-in mouse model genetically engineered to express human IL-15 uniquely supported the growth of SS patient samples relative to conventional immunodeficient mouse strains. SS patient-derived xenograft (PDX) models recapacitated key pathological features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single-cell transcriptomic analysis revealed congruent neoplastic gene expression signatures but distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of immunodeficient humanized IL-15 mice as hosts for SS - and potentially other T and NK cell-derived hematologic malignancies - PDX model generation. Furthermore, these studies advocate the thorough molecular understanding of the resultant PDX models to maximize their translational impact.
Topics: Humans; Animals; Mice; Skin Neoplasms; Interleukin-15; Lymphoma, T-Cell, Cutaneous; Sezary Syndrome; Lymphocytes; Tumor Microenvironment
PubMed: 37718909
DOI: 10.1242/dmm.050190 -
Cancer Management and Research 2023Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach... (Review)
Review
Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach to management. The most common subtype is mycosis fungoides, in which local disease has an excellent prognosis and is often managed with topical therapy alone. More extensive cutaneous involvement as well as involvement of lymph nodes and the peripheral blood (Sezary syndrome) require systemic therapies. Recent years have brought an expansion of therapeutic options, specifically with immune-based approaches that were developed using the knowledge gained regarding the biology and molecular pathology of CTCL. Previous systemic therapies such as retinoids, histone deacetylase inhibitors, and chemotherapeutic agents come with significant toxicity and only short-term response. Newer agents such as mogamulizumab and brentuximab vedotin use a targeted immune-based approach leading to longer periods of response with less systemic toxicity. While still in its infancy, the use of immune checkpoint inhibitors such as nivolumab and pembrolizumab appears promising, and while their current clinical application is limited, early data suggest possible future areas for research of immune manipulation to treat CTCL. Herein, we review these novel immune-based treatment strategies, their superiority over prior systemic options, and the ongoing need for further research and clinical trial enrollment.
PubMed: 37700809
DOI: 10.2147/CMAR.S330908