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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 -
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 -
The British Journal of Dermatology Nov 2021Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking.
Mycosis fungoides-derived exosomes promote cell motility and are enriched with microRNA-155 and microRNA-1246, and their plasma-cell-free expression may serve as a potential biomarker for disease burden.
BACKGROUND
Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking.
OBJECTIVES
To characterize MF-derived exosomes and their involvement in the disease.
METHODS
Exosomes were isolated by ultracentrifugation from cutaneous T-cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell-line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma-cell-free microRNA (cfmiRNA) were analysed by reverse-transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay.
RESULTS
MyLa- and MJ-derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)-155 and miR-1246. Both microRNAs were delivered into target cells, but only exomiR-155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR-1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR-155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR-1246 (and not exomiR-155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration.
CONCLUSIONS
Our findings show that MF-derived exosomes promote cell motility and are enriched with miR-155, a well-known microRNA in MF, and miR-1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden.
Topics: Biomarkers, Tumor; Cell Movement; Exosomes; Humans; MicroRNAs; Mycosis Fungoides; Skin Neoplasms
PubMed: 34053079
DOI: 10.1111/bjd.20519 -
Acta Dermato-venereologica Jun 2022Chlormethine is a bifunctional cytotoxic alkylating agent that binds to DNA, resulting in cell death (apoptosis). Chlormethine (also known as mechlorethamine) gel (CL...
Chlormethine is a bifunctional cytotoxic alkylating agent that binds to DNA, resulting in cell death (apoptosis). Chlormethine (also known as mechlorethamine) gel (CL gel) was approved in the European Union in 2017 and was first used in 2019. The aim of the study is to examine evidence regarding the efficacy and safety of chlormethine gel in everyday clinical experience from a cutaneous lymphoma centre. Twenty-three patients with stage IA-IIB mycosis fungoides received chlormethine gel between September 2020 and May 2021. All patients started by applying the gel daily and were monitored every month. At 1, 3, 6 and 9 months, 0%, 43.47%, 56.52% and 65.22% of patients, respectively, achieved an overall response. Five out of 23 patients (21.73%) achieved near complete response at a mean time of 6 months. Chlormethine gel was given as monotherapy in 12 patients (52.17%), and in addition to systemic treatments (methotrexate and peginterferon alpha-2a) in 11 patients (47.82%). Adverse events (AE) were recorded in 43.47% of patients, but only 3 discontinued treatment, due to dermatitis. Scale down of the treatment to application 3-times per week led to better patient compliance. This study shows that chlormethine gel is effective and safe in patients with mycosis fungoides with different types of skin lesions.
Topics: Antineoplastic Agents; Antineoplastic Agents, Alkylating; Humans; Mechlorethamine; Mycosis Fungoides; Skin Diseases; Skin Neoplasms
PubMed: 35199177
DOI: 10.2340/actadv.v102.1095 -
Dermatologic Clinics Oct 2015Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous,... (Review)
Review
Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous, they can be indistinguishable histologically. Lymphomatoid papulosis rarely requires systemic treatment; however, multifocal primary cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation of mycosis fungoides are typically treated systemically. As CD30⁺ LPDs are rare, there is little published evidence to support a specific treatment algorithm. Most studies are case reports, small case series, or retrospective reviews. This article discusses various treatment choices for each of the CD30⁺ disorders and offers practical pearls to aid in choosing an appropriate regimen.
Topics: Antineoplastic Agents; Cell Transformation, Neoplastic; Combined Modality Therapy; Diagnosis, Differential; Humans; Ki-1 Antigen; Lymphoma, Primary Cutaneous Anaplastic Large Cell; Lymphomatoid Papulosis; Mycosis Fungoides; Prognosis; Skin Neoplasms
PubMed: 26433852
DOI: 10.1016/j.det.2015.05.013 -
Drug Design, Development and Therapy 2018Nitrogen mustard is a chemotherapeutic agent that has a well-documented safety and efficacy profile in the treatment of cutaneous T-cell lymphoma. Development of... (Review)
Review
Nitrogen mustard is a chemotherapeutic agent that has a well-documented safety and efficacy profile in the treatment of cutaneous T-cell lymphoma. Development of nitrogen mustard formulations and treatment regimens has been studied extensively over the last 40 years. In the last 5 years, a new gel formulation has been developed that is associated with a decrease in delayed hypersensitivity reactions. The authors in this review found that while the gel formulation may result in a decrease of allergic contact dermatitis, this advantage has been replaced by a higher number of irritant contact reactions and a decrease in complete response rate. The gel formulation has a complete response rate of 13.8%, which is a decrease in efficacy when compared to aqueous-based preparations of similar concentrations.
Topics: Administration, Cutaneous; Antineoplastic Agents, Alkylating; Drug Eruptions; Gels; Humans; Mechlorethamine; Mycosis Fungoides; Risk Factors; Skin Neoplasms; Treatment Outcome
PubMed: 29440874
DOI: 10.2147/DDDT.S137106 -
Cells Mar 2022Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Early-stage disease is characterized by superficial infiltrates of small- to medium-sized...
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Early-stage disease is characterized by superficial infiltrates of small- to medium-sized atypical epidermotropic T lymphocytes that are clonal related. Nevertheless, the percentage of atypical T cells is low with many admixed reactive immune cells. Despite earlier studies, the composition and spatial characteristics of the cutaneous lymphocytic infiltrate has been incompletely characterized. Here, we applied mass cytometry to profile the immune system in skin biopsies of patients with early-stage MF and in normal skin from healthy individuals. Single-cell suspensions were prepared and labeled with a 43-antibody panel, and data were acquired on a Helios mass cytometer. Unbiased hierarchical clustering of the data identified the major immune lineages and heterogeneity therein. This revealed patient-unique cell clusters in both the CD4 and myeloid cell compartments but also phenotypically distinct cell clusters that were shared by most patients. To characterize the immune compartment in the tissue context, we developed a 36-antibody panel and performed imaging mass cytometry on MF skin tissue. This visualized the structure of MF skin and the distribution of CD4 T cells, regulatory T cells, CD8 T cells, malignant T cells, and various myeloid cell subsets. We observed clusters of CD4 T cells and multiple types of dendritic cells (DCs) identified through differential expression of CD11c, CD1a, and CD1c in the dermis. These results indicated substantial heterogeneity in the composition of the local immune infiltrate but suggest a prominent role for clustered CD4-DC interactions in disease pathogenesis. Probably, the local inhibition of such interactions may constitute an efficient treatment modality.
Topics: CD8-Positive T-Lymphocytes; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Skin; Skin Neoplasms
PubMed: 35406628
DOI: 10.3390/cells11071062 -
Saudi Medical Journal Sep 2016To evaluate the effect of pregnancy on the natural course of Mycosis fungoides (MF) and compare the obtained results with previous reports.
OBJECTIVES
To evaluate the effect of pregnancy on the natural course of Mycosis fungoides (MF) and compare the obtained results with previous reports.
METHODS
The medical records of 140 patients with cutaneous T-cell lymphoma (CTCL) treated at the University Hospital of Isfahan (the academic referral center for CTCL) Isfahan, Iran. Between 2000 and 2013 were retrospectively reviewed to retrieve all cases of pregnancy during the course of MF disease.
RESULTS
A total of 8 pregnancies were recorded. The median age of patients at the time of diagnosis was 26.7 (range 21-30 years) and pregnancy 29.4 (range 27-31 years). Most of patients had early-stage MF (Ia and Ib). All patients experienced aggravation of disease during pregnancy or immediately postpartum. Mycosis fungoides did not cause any complications during pregnancy.
CONCLUSION
Pregnancy appears to have a negative impact on the course of MF, probably due to immune system deteriorations during the pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF.
Topics: Adult; Female; Humans; Mycosis Fungoides; Pregnancy; Pregnancy Complications, Neoplastic; Retrospective Studies
PubMed: 27570852
DOI: 10.15537/smj.2016.9.15838 -
Frontiers in Immunology 2020Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have...
BACKGROUND
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.
METHODS
Whole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.
RESULTS
MF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.
CONCLUSIONS
The neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Clonal Evolution; Computational Biology; Disease Management; Disease Progression; Disease Susceptibility; Female; Gene Expression Profiling; Humans; Male; Mutation; Mycosis Fungoides; Neoplasm Staging; Peptides; Transcriptome; Exome Sequencing
PubMed: 33329522
DOI: 10.3389/fimmu.2020.561234 -
Anais Brasileiros de Dermatologia 2021Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. Most early-stage mycosis fungoides cases follow an indolent course, hence considered by doctors a...
BACKGROUND
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. Most early-stage mycosis fungoides cases follow an indolent course, hence considered by doctors a relatively easy condition. However, since mycosis fungoides bears the title of cancer, patients might perceive it differently.
OBJECTIVE
To investigate patients' illness perception, and its relationships to quality of life, depression, anxiety, and coping among early-stage mycosis fungoides patients.
METHODS
A cross-sectional questionnaire-based study was conducted. Patients from a single tertiary medical center completed the Revised Illness Perception Questionnaire, the MF/SS-CTCL Quality of Life scale, the Hospital Anxiety and Depression Scale, and The Mental Adjustment to Cancer Scale.
RESULTS
Thirty patients (25 males, five females, mean age 51.60) with stage I mycosis fungoides were enrolled. Mycosis fungoides had a little impact on patients' daily life, quality of life, and levels of depression and anxiety, and they generally coped well. Disease understanding was low and was negatively correlated with impairment to quality of life and depression. Patients felt that stress and worry were features of the disease's etiology.
STUDY LIMITATIONS
A small sample of patients was included.
CONCLUSION
Patients with early-stage mycosis fungoides adapt well to their disease. Psychological interventions should be aimed at improving patients coping style and enhancing illness understanding, in order to maintain high quality of life.
Topics: Adaptation, Psychological; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Perception; Quality of Life; Skin Neoplasms
PubMed: 33279315
DOI: 10.1016/j.abd.2020.05.008