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Turkish Journal of Haematology :... Mar 2018Transformed mycosis fungoides (T-MF) is a rare variant of MF with an aggressive course. In this study, we aimed to describe characteristics of MF/Sezary syndrome (SS)...
OBJECTIVE
Transformed mycosis fungoides (T-MF) is a rare variant of MF with an aggressive course. In this study, we aimed to describe characteristics of MF/Sezary syndrome (SS) patients with transformation.
MATERIALS AND METHODS
Patients diagnosed with T-MF among MF/SS patients between 2000 and 2014 in a tertiary single center were evaluated retrospectively. Demographic data, clinical data, laboratory data, immunophenotype features, response to treatment, survival, and histopathologic features were analyzed.
RESULTS
Among 254 MF patients, 25 patients with T-MF were identified (10.2%) and included in the study. The male-to-female ratio was 2.6/1. The median time between MF diagnosis and transformation was 32 months (range: 0-192). Nine (36%) patients were diagnosed initially with T-MF. Advanced disease stage and high serum lactate dehydrogenase (LDH) levels were indicators of poor prognosis and treatment response. Five of the 18 patients with progressive disease had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT resulted in complete remission in three (60%) patients. Ten (40%) patients died as a result of disease progression. Mean survival time was 25.2±14.9 (2-56) months after transformation.
CONCLUSION
Advanced stage, high serum LDH levels, and loss of CD26 and CD7 expression in the peripheral blood are poor rognostic factors in T-MF. Treatment-resistant tumors and nodules should be cautionary for T-MF. Patients with T-MF have a shortened survival. Some patients may respond to first-line treatments. However, the majority of patients who do not respond to first-line therapies also are unresponsive to second or third-line therapies. Allo-HSCT may be an alternative option in patients with T-MF.
Topics: Adult; Aged; Biomarkers; Combined Modality Therapy; Female; Humans; Immunophenotyping; Kaplan-Meier Estimate; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Prognosis; Retrospective Studies; Risk Factors; Sezary Syndrome; Skin; Skin Neoplasms
PubMed: 28533196
DOI: 10.4274/tjh.2016.0502 -
Cells Aug 2020Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells,... (Review)
Review
Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells, erythroderma and lymphadenopathy. However, highly variable clinical skin manifestations and similarities with benign mimickers can lead to significant diagnostic delay and inappropriate therapy that can lead to disease progression and mortality. SS has been the focus of numerous transcriptomic-profiling studies to identify sensitive and specific diagnostic and prognostic biomarkers. Benign inflammatory disease controls (e.g., psoriasis, atopic dermatitis) have served to identify chronic inflammatory phenotypes in gene expression profiles, but provide limited insight into the lymphoproliferative and oncogenic roles of abnormal gene expression in SS. This perspective was recently clarified by a transcriptome meta-analysis comparing SS and lymphocytic-variant hypereosinophilic syndrome, a benign yet often clonal T-cell lymphoproliferation, with clinical features similar to SS. Here we review the rationale for selecting lymphocytic-variant hypereosinophilic syndrome (L-HES) as a disease control for SS, and discuss differentially expressed genes that may distinguish benign from malignant lymphoproliferative phenotypes, including additional context from prior gene expression studies to improve understanding of genes important in SS.
Topics: Biomarkers; Gene Expression; Humans; Hypereosinophilic Syndrome; Sezary Syndrome
PubMed: 32872487
DOI: 10.3390/cells9091992 -
International Journal of Molecular... Mar 2024Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell... (Review)
Review
Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases.
Topics: Humans; Photopheresis; Skin Neoplasms; Mycosis Fungoides; Blood Component Removal; Sezary Syndrome
PubMed: 38474257
DOI: 10.3390/ijms25053011 -
BMC Health Services Research Feb 2021Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.
BACKGROUND
Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.
METHODS
In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998-2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland.
RESULTS
The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998-2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up.
CONCLUSIONS
The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998-2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.
Topics: Delivery of Health Care; Finland; Humans; Mycosis Fungoides; Prevalence; Sezary Syndrome; Skin Neoplasms
PubMed: 33618714
DOI: 10.1186/s12913-021-06109-9 -
Cells Oct 2021Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. It has been hypothesized that the interaction between the immune system,... (Review)
Review
BACKGROUND
Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. It has been hypothesized that the interaction between the immune system, cutaneous cells, and neoplastic elements may play a role in MF/SS pathogenesis and progression.
METHODS
This paper aims to revise in a narrative way our current knowledge of the microenvironment's role in MF/SS.
RESULTS AND CONCLUSIONS
Literature data support a possible implication of microenvironment cells in MF/SS pathogenesis and progression, opening up new therapeutic avenues.
Topics: Animals; Disease Progression; Humans; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Tumor Microenvironment
PubMed: 34685762
DOI: 10.3390/cells10102780 -
Dermatologic Clinics Oct 2015Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune... (Review)
Review
Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune response in cutaneous T-cell lymphoma (CTCL). Because of its excellent side effect profile and moderate efficacy, ECP is considered first-line therapy for erythrodermic mycosis fungoides (MF) and Sézary syndrome. Patients with a measurable but low blood tumor burden are most likely to respond to ECP, and the addition of adjunctive immunostimulatory agents may also increase response rates. There may be a role for ECP in the treatment of refractory early stage MF, but data are limited.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Humans; Immunomodulation; Methoxsalen; Mycosis Fungoides; Photopheresis; Photosensitizing Agents; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 26433848
DOI: 10.1016/j.det.2015.05.011 -
Blood Nov 2009The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and... (Review)
Review
The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a "stage-based" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.
Topics: Antineoplastic Agents; Combined Modality Therapy; Humans; Mycosis Fungoides; Radiotherapy; Sezary Syndrome; Skin Neoplasms
PubMed: 19696197
DOI: 10.1182/blood-2009-07-202895 -
Cytometry. Part B, Clinical Cytometry May 2022Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping...
BACKGROUND
Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death-1 (PD-1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry.
METHODS
50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD-1 was assessed over time in blood and bone marrow of available MF/SS cases.
RESULTS
Normal CD4+ T cells showed dim/intermediate to absent PD-1 expression. PD-1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD-1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD-1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan-T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD-1 remained informative in blood/bone marrow over time in most patients.
CONCLUSIONS
PD-1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.
Topics: Biomarkers; Dipeptidyl Peptidase 4; Flow Cytometry; Humans; Mycosis Fungoides; Programmed Cell Death 1 Receptor; Sezary Syndrome; Skin Neoplasms
PubMed: 35451196
DOI: 10.1002/cyto.b.22070 -
The Journal of Investigative Dermatology Sep 2016Sézary syndrome (Sz) is a malignancy of skin-homing CD4(+) memory T cells that is clinically characterized by erythroderma, lymphadenopathy, and blood involvement.... (Comparative Study)
Comparative Study Review
Sézary syndrome (Sz) is a malignancy of skin-homing CD4(+) memory T cells that is clinically characterized by erythroderma, lymphadenopathy, and blood involvement. Distinction of Sz from erythroderma secondary to inflammatory skin diseases (erythrodermic inflammatory dermatosis [EID]) is often challenging. Recent studies identified recurrent mutations in epigenetic enzymes involved in DNA modification in Sz. Here we defined the DNA methylomes of purified CD4(+) T cells from patients with Sz, EID, and healthy control subjects. Sz showed extensive global DNA methylation alterations, with 7.8% of 473,921 interrogated autosomal CpG sites showing hypomethylation and 3.2% hypermethylation. Promoter CpG islands were markedly enriched for hypermethylation. The 126 genes with recurrent promoter hypermethylation in Sz included multiple candidate tumor suppressors that showed transcriptional repression, implicating aberrant methylation in the pathogenesis of Sz. Validation in an independent sample set showed promoter hypermethylation of CMTM2, C2orf40, G0S2, HSPB6, PROM1, and PAM in 94-100% of Sz samples but not in EID samples. Notably, promoter hypermethylation of a single gene, the chemokine-like factor CMTM2, was sufficient to accurately distinguish Sz from EID in all cases. This study shows that Sz is characterized by widespread yet distinct DNA methylation alterations, which can be used clinically as epigenetic diagnostic markers.
Topics: Aged; Biomarkers, Tumor; Case-Control Studies; Cell Line, Tumor; DNA Methylation; Epigenomics; Female; Gene Expression Regulation, Neoplastic; Genome-Wide Association Study; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Promoter Regions, Genetic; Sezary Syndrome; Skin Neoplasms
PubMed: 27113428
DOI: 10.1016/j.jid.2016.03.042 -
Anais Brasileiros de Dermatologia 2012This paper reviews the diagnostic and classificatory concepts of mycosis fungoides and Sézary syndrome in light of the latest normative publications. It describes the... (Review)
Review
This paper reviews the diagnostic and classificatory concepts of mycosis fungoides and Sézary syndrome in light of the latest normative publications. It describes the great variability of the clinical expression of mycosis fungoides in its early stages as well as the histopathological and immunohistochemical aspects that help with diagnosis. The diagnostic criteria required for characterizing Sézary syndrome and the staging system used for both mycosis fungoides and Sézary syndrome are described.
Topics: Diagnosis, Differential; Female; Humans; Male; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 23197199
DOI: 10.1590/s0365-05962012000600001