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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 -
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 -
Dermatologic Clinics Oct 2015Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on... (Review)
Review
Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on clinical lesion type and evaluation of findings on light microscopic examination, immunohistochemistry and molecular analysis of representative skin biopsies. The evaluation, classification, and staging system is unique for mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of cutaneous T-cell lymphoma (CTCL) versus the other subtypes of Non-MF/Non-SS CTCL and the subtypes of cutaneous B-cell lymphoma (CBCL). Since current treatment is stage-based, it is particularly important that the correct diagnosis and stage be ascertained initially. The purpose of this article is to review the current evaluation, diagnosis, classification, staging, assessment techniques, and response criteria for the various types of both T-cell and B-cell PCLs.
Topics: Humans; Lymphoma, B-Cell; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin Neoplasms
PubMed: 26433839
DOI: 10.1016/j.det.2015.06.001 -
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 -
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 -
Oncology (Williston Park, N.Y.) May 2010Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly... (Review)
Review
Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF's nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.
Topics: Humans; Mycosis Fungoides; Neoplasm Staging; Skin Neoplasms
PubMed: 20568590
DOI: No ID Found -
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 -
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 -
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 -
Yonsei Medical Journal Dec 1991Within the past few years, an increasing number of reports of Hodgkin's disease following the diagnosis of, and frequently coexisting with, mycosis fungoides have... (Review)
Review
Within the past few years, an increasing number of reports of Hodgkin's disease following the diagnosis of, and frequently coexisting with, mycosis fungoides have appeared. Previously, Hodgkin's disease found in the lymph nodes of the patient diagnosed as mycosis fungoides was considered as a transformed form of the mycosis fungoides. But, now it has been proven that Hodgkin's disease and mycosis fungoides are histologically and immunohistochemically distinct disease entities. We report a well-documented case of a man who developed Hodgkin's disease and mycosis fungoides simultaneously as a composite lymphoma. Our case emphasizes the importance of considering the diagnosis of another lymphoma in patients with mycosis fungoides who have lymphadenopathy. The cutaneous mycosis fungoides and the Hodgkin's disease should be treated as an independent disease.
Topics: Adult; Hodgkin Disease; Humans; Male; Mycosis Fungoides; Neoplasms, Multiple Primary; Skin Neoplasms
PubMed: 1812658
DOI: 10.3349/ymj.1991.32.4.362