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Blood Aug 2022The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical...
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
Topics: Clinical Trials as Topic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Sezary Syndrome; Skin Neoplasms; United States
PubMed: 34758074
DOI: 10.1182/blood.2021012057 -
Oncology Research and Treatment 2017
Topics: Drug Therapy; Humans; Mycosis Fungoides; Photochemotherapy; Radiotherapy Dosage; Radiotherapy, High-Energy; Sezary Syndrome; Skin Neoplasms
PubMed: 28423383
DOI: 10.1159/000475528 -
Chinese Clinical Oncology Feb 2019Sezary syndrome (SS) is a primary cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, lymphadenopathy and leukemic involvement of the peripheral blood. The... (Review)
Review
Sezary syndrome (SS) is a primary cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, lymphadenopathy and leukemic involvement of the peripheral blood. The high relapse rates and a poor prognosis complicate its clinical course and treatment. The phenotypic characterization and genomic/transcriptomic approaches revealed high heterogeneity of Sezary cells, identifying a wide spectrum of biomarkers implicated in the development of this lymphoma. In this context, we discuss the major malignancy-related biomarkers reported in the literature for the diagnosis, prognosis and staging of SS. The hope for a single reliable diagnostic marker appears increasingly unrealistic, but the discovery of multiple potential biomarkers, with pathogenetic implications, paves the road to promising personalized therapies in SS.
Topics: Biomarkers; Humans; Prognosis; Sezary Syndrome
PubMed: 30525758
DOI: 10.21037/cco.2018.11.02 -
Nature Communications Nov 2021Cutaneous T cell lymphomas (CTCL) are rare but aggressive cancers without effective treatments. While a subset of patients derive benefit from PD-1 blockade, there is a...
Cutaneous T cell lymphomas (CTCL) are rare but aggressive cancers without effective treatments. While a subset of patients derive benefit from PD-1 blockade, there is a critically unmet need for predictive biomarkers of response. Herein, we perform CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions from 14 advanced CTCL patients enrolled in a pembrolizumab clinical trial (NCT02243579). We find no differences in the frequencies of immune or tumor cells between responders and non-responders. Instead, we identify topographical differences between effector PD-1 CD4 T cells, tumor cells, and immunosuppressive Tregs, from which we derive a spatial biomarker, termed the SpatialScore, that correlates strongly with pembrolizumab response in CTCL. The SpatialScore coincides with differences in the functional immune state of the tumor microenvironment, T cell function, and tumor cell-specific chemokine recruitment and is validated using a simplified, clinically accessible tissue imaging platform. Collectively, these results provide a paradigm for investigating the spatial balance of effector and suppressive T cell activity and broadly leveraging this biomarker approach to inform the clinical use of immunotherapies.
Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; CD4-Positive T-Lymphocytes; Female; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphocyte Activation; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Mycosis Fungoides; Programmed Cell Death 1 Receptor; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 34795254
DOI: 10.1038/s41467-021-26974-6 -
Blood Oct 2021
Topics: Flow Cytometry; Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 34673947
DOI: 10.1182/blood.2021012016 -
Cytometry. Part B, Clinical Cytometry Mar 2021This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in... (Review)
Review
This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in their diagnosis. The following key points are raised: (a) Sézary syndrome and mycosis fungoides cells most often have a characteristic CD3+ CD4+ CD7- and/or CD26- immunophenotype. (b) This immunophenotype is not specific, but can assist in the distinction from non-neoplastic T cells and other subtypes of mature T-cell neoplasm. (c) However, small subsets of normal and reactive T-cells can have an overlapping immunophenotype, and can be distinguished by evaluating for additional changes in antigen expression.
Topics: Antigens, CD; Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32516521
DOI: 10.1002/cyto.b.21888 -
Cytometry. Part B, Clinical Cytometry Mar 2021Flow cytometry of peripheral blood has become the standard tool for the diagnosis and monitoring of Sézary syndrome. However, there is a sense of frustration among... (Review)
Review
Flow cytometry of peripheral blood has become the standard tool for the diagnosis and monitoring of Sézary syndrome. However, there is a sense of frustration among dermatologists and oncologist regarding the challenges in interpreting vague flow cytometry (FC) reports, which often include an array of numbers and percentages that are difficult to interpret and fail to elucidate quantitatively or qualitatively the presence or absence of an abnormal T cell population. From the clinicians' perspective, a report of the flow cytometric evaluation for Sézary syndrome should include the following items: presence or absence of abnormal T-cells, phenotype of abnormal cells, and quantity of abnormal cells to disease burden and for staging.
Topics: Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32017375
DOI: 10.1002/cyto.b.21870 -
Cytometry. Part B, Clinical Cytometry Mar 2021
Topics: Antigens, CD; Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32083391
DOI: 10.1002/cyto.b.21872 -
Blood Dec 2021
Topics: Gene Expression Profiling; Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 34914833
DOI: 10.1182/blood.2021013433 -
International Journal of Molecular... Mar 2022Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic... (Review)
Review
Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic system. Cutaneous malignancies are usually affected by epigenetic changes. However, there is limited knowledge regarding the epigenetic changes associated with cutaneous lymphomas. In this review, we focused on cutaneous T-cell lymphomas such as mycosis fungoides, Sézary syndrome, and anaplastic large cell lymphoma. With regard to epigenetic changes, we summarize the detailed chemical modifications categorized into DNA methylation and histone acetylation and methylation. We also summarize the epigenetic modifications and characteristics of the drug for cutaneous T-cell lymphoma (CTCL). Furthermore, we discuss current research on epigenetic-targeted therapy against cutaneous T-cell lymphomas. Although the current method of treatment with histone deacetylase inhibitors does not exhibit sufficient therapeutic benefits in all cases of CTCL, epigenetic-targeted combination therapy might overcome this limitation for patients with CTCL.
Topics: Epigenesis, Genetic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 35408897
DOI: 10.3390/ijms23073538