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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 -
Cancers Apr 2023Mycosis fungoides (MF) and Sézary syndrome (SS) are two closely related clinical variants of cutaneous T-cell lymphomas (CTCL). Previously demonstrated large... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are two closely related clinical variants of cutaneous T-cell lymphomas (CTCL). Previously demonstrated large patient-to-patient and intra-patient disease heterogeneity underpins the importance of personalized medicine in CTCL. Advanced stages of CTCL are characterized by dismal prognosis, and the early identification of patients who will progress remains a clinical unmet need. While the exact molecular events underlying disease progression are poorly resolved, the tumor microenvironment (TME) has emerged as an important driver. In particular, the Th1-to-Th2 shift in the immune response is now commonly identified across advanced-stage CTCL patients. Herein, we summarize the role of the TME in CTCL evolution and the latest studies in deciphering inter- and intra-patient heterogeneity. We introduce spatially resolved omics as a promising technology to advance immune-oncology efforts in CTCL. We propose the combined implementation of spatially guided and single-cell omics technologies in paired skin and blood samples. Such an approach will mediate in-depth profiling of phenotypic and molecular changes in reactive immune subpopulations and malignant T cells preceding the Th1-to-Th2 shift and reveal mechanisms underlying disease progression from skin-limited to systemic disease that collectively will lead to the discovery of novel biomarkers to improve patient prognostication and the design of personalized treatment strategies.
PubMed: 37190290
DOI: 10.3390/cancers15082362 -
International Journal of Molecular... Nov 2021Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, including various clinical manifestations, such as mycosis fungoides (MF) and Sézary... (Review)
Review
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, including various clinical manifestations, such as mycosis fungoides (MF) and Sézary syndrome (SS). CTCL mostly develops from CD4 T cells with the skin-tropic memory phenotype. Malignant T cells in MF lesions show the phenotype of skin resident memory T cells (T), which reside in the peripheral tissues for long periods and do not recirculate. On the other hand, malignant T cells in SS represent the phenotype of central memory T cells (T), which are characterized by recirculation to and from the blood and lymphoid tissues. The kinetics and the functional characteristics of malignant cells in CTCL are still unclear due, in part, to the fact that both the malignant cells and the T cells exerting anti-tumor activity possess the same characteristics as T cells. Capturing the features of both the malignant and the benign T cells is necessary for understanding the pathogenesis of CTCL and would lead to new therapeutic strategies specifically targeting the skin malignant T cells or benign T cells.
Topics: Animals; Humans; Lymphoma, T-Cell, Cutaneous; Memory T Cells; Skin; Tumor Microenvironment
PubMed: 34884736
DOI: 10.3390/ijms222312933 -
Blood Advances Mar 2022Sezary syndrome (SS) is a rare leukemic form of cutaneous T-cell lymphoma. Diagnosis mainly depends on flow cytometry, but results are not specific enough to be...
Sezary syndrome (SS) is a rare leukemic form of cutaneous T-cell lymphoma. Diagnosis mainly depends on flow cytometry, but results are not specific enough to be unequivocal. The difficulty in defining a single marker that could characterize Sezary cells may be the consequence of different pathological subtypes. In this study, we used multivariate flow cytometry analyses. We chose to investigate the expression of classical CD3, CD4, CD7, and CD26 and the new association of 2 markers CD158k and PD-1. We performed lymphocyte computational phenotypic analyses during diagnosis and follow-up of patients with SS to define new SS classes and improve the sensitivity of the diagnosis and the follow-up flow cytometry method. Three classes of SS, defined by different immunophenotypic profiles, CD158k+ SS, CD158k-PD-1+ SS, CD158k and PD-1 double-negative SS, showed different CD8+ and B-cell environments. Such a study could help to diagnose and define biological markers of susceptibility/resistance to treatment, including immunotherapy.
Topics: Biomarkers, Tumor; Humans; Programmed Cell Death 1 Receptor; Receptors, KIR2DL2; Receptors, KIR3DL2; Sezary Syndrome; Skin Neoplasms
PubMed: 34570200
DOI: 10.1182/bloodadvances.2021005147 -
JAAD Case Reports Mar 2021
PubMed: 33644277
DOI: 10.1016/j.jdcr.2020.12.033 -
Blood Mar 2022Cutaneous T-cell lymphomas (CTCLs) are rare malignancies involving primarily the skin. Responses to treatment are usually short-lived in advanced CTCL. The determinants...
Cutaneous T-cell lymphomas (CTCLs) are rare malignancies involving primarily the skin. Responses to treatment are usually short-lived in advanced CTCL. The determinants of long-term CTCL control are unclear. Mogamulizumab, an anti-human CCR4 antibody that acts by antibody-dependent cell cytotoxicity against CCR4+ CTCL tumor cells and peripheral memory blood regulatory T cells, has been associated with long-lasting remissions and immune adverse events. Here, we reported skin rashes in 32% of 44 patients with CTCL treated with mogamulizumab, associated with significantly higher overall survival (hazard ratio, 0.16; 0.04-0.73; P = .01). Rash occurred in patients with Sézary syndrome and was associated with longer time to progression. These rashes were characterized by a CD163+ granulomatous and/or CD8+ lichenoid skin infiltrate. High-throughput sequencing analysis of T-cell receptor β genes in skin and blood flow cytometry confirmed the depletion of CTCL tumor cells, as well as the recruitment of new reactive T-cell clones in skin at the time of skin rash. CXCL9 and CXCL11, two macrophage-derived chemokines that recruit CXCR3+ T cells to skin, were overexpressed in skin rashes. A higher frequency of TIGIT+ and PD1+ exhausted reactive blood T cells was observed at baseline in patients with rash, and this frequency decreased with mogamulizumab treatment. These data are consistent with mogamulizumab-induced long-term immune CTCL control by activation of the macrophage and T-cell responses in patients with rash.
Topics: Antibodies, Monoclonal, Humanized; Chemokine CXCL11; Chemokine CXCL9; Exanthema; Humans; Lymphoma, T-Cell, Cutaneous; Macrophages; Skin Neoplasms; T-Lymphocytes, Regulatory
PubMed: 34905599
DOI: 10.1182/blood.2021013341 -
International Journal of Molecular... Oct 2021Primary cutaneous lymphomas are heterogenous lymphoproliferative disorders. Some patients show rapid progression and the need for treatment of advanced disease is still... (Review)
Review
Primary cutaneous lymphomas are heterogenous lymphoproliferative disorders. Some patients show rapid progression and the need for treatment of advanced disease is still unmet. The frequency of each subtype of cutaneous lymphoma varies among different ethnic groups, as do the medical systems found in different countries. It is important to know the differences in clinical guidelines in different areas of the world. Although current monochemotherapy with gemcitabine or pegylated liposomal doxorubicin is temporarily effective for mycosis funogides (MF) and Sézary syndrome (SS)-representative types of cutaneous lymphomas-the duration of response is usually limited. Therefore, treatment strategies targeting tumor-specific molecules have been developed. Molecular targets for MS/SS are currently CD30, CCR4, CD25, CD52, and histone deacetylases, most of which are surface molecules specifically expressed on tumor cells. As a result of advances in research techniques, different kinds of genomic alterations in MF/SS have been revealed. Molecular targets for MS/SS in the near future would be CD158k, JAK, PIK3, the mammalian target of rapamycin, and microRNAs, most of which mediate intracellular signaling pathways. Personalized therapy based on the detection of the genetic signatures of tumors and inhibition of the most suitable target molecules constitutes a future treatment strategy for MF/SS.
Topics: Europe; Histone Deacetylases; Humans; Interleukin-2 Receptor alpha Subunit; Japan; Ki-1 Antigen; Lymphoma; MicroRNAs; Molecular Targeted Therapy; Practice Guidelines as Topic; Precision Medicine; Receptors, CCR4; Sezary Syndrome; Skin Neoplasms
PubMed: 34681738
DOI: 10.3390/ijms222011079 -
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 -
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 -
Genes May 2024Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin.... (Review)
Review
Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin. Sézary syndrome (SS) is an aggressive and rare form of cutaneous T cell lymphoma (CTCL) characterized by an erythroderma and the presence of atypical cerebriform T cells named Sézary cells in skin and blood. Most of the available treatments for SS are not curative, which means there is an urgent need for the development of novel efficient therapies. Recently, targeting cancer metabolism has emerged as a promising strategy for cancer therapy. This is due to the accumulating evidence that metabolic reprogramming highly contributes to tumor progression. Genes play a pivotal role in regulating metabolic processes, and alterations in these genes can disrupt the delicate balance of metabolic pathways, potentially contributing to cancer development. In this review, we discuss the importance of targeting energy metabolism in tumors and the currently available data on the metabolism of Sézary cells, paving the way for potential new therapeutic approaches aiming to improve clinical outcomes for patients suffering from SS.
Topics: Humans; Sezary Syndrome; Skin Neoplasms; Energy Metabolism; Animals
PubMed: 38790264
DOI: 10.3390/genes15050635