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Frontiers in Oncology 2023Sézary Syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL). In SS patients, malignant T cells are circulating through the blood and...
BACKGROUND
Sézary Syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL). In SS patients, malignant T cells are circulating through the blood and cause erythroderma.
OBJECTIVE
To compare the transcriptome of single cells in blood and skin samples from a patient with advanced SS.
METHODS
We utilized combined single cell RNA and T-cell receptor (TCR) sequencing (scRNA-seq).
RESULTS
We scrutinized the malignant T cells in blood and skin in an unbiased manner without pre-sorting of cells. We observed different phenotypes of the same monoclonal malignant T-cell population, confirmed by TCR sequencing and inferred copy number variation analysis. Malignant T cells present in the circulating blood expressed genes resembling central memory T cells such as , and . In the skin, we detected two major malignant T-cell populations: One subpopulation was closely related to the malignant T cells from the blood, while the other subpopulation expressed genes reminiscent of skin resident effector memory T cells including and . Pseudotime analysis indicated crucial transcriptomic changes in the transition of malignant T cells between blood and skin. These changes included the differential regulation of , a putative tumor suppressor in CTCL, and the adaptation to the hypoxic conditions in the skin. Tumor cell proliferation in the skin was supported by stimulating interactions between myeloid cells and malignant T cells.
CONCLUSIONS
Using scRNA-seq we detected a high degree of functional heterogeneity within the malignant T-cell population in SS and highlighted crucial differences between SS cells in blood and skin.
PubMed: 36761972
DOI: 10.3389/fonc.2023.1090592 -
JAAD International Mar 2023
PubMed: 36655210
DOI: 10.1016/j.jdin.2022.11.005 -
Cureus Dec 2022Medicines often cause serious immune-mediated mucocutaneous reactions including Steven-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). In the acute phase of...
Medicines often cause serious immune-mediated mucocutaneous reactions including Steven-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). In the acute phase of SJS and TEN, a febrile illness is followed by cutaneous erythema with blister formation, skin and mucous membrane necrosis, and separation of the skin and mucous membranes. The patient swiftly becomes in danger of dying, necessitating immediate medical attention. In this case report, we described a case of Steven-Johnson Syndrome in a 102-year-old female who was receiving palliative care and had stage 5 chronic renal disease. Although the agent that caused SJS in this patient is unknown, the patient was managed with topical medication, bandages for the lesions, and oral antihistamines. Skin biopsy, abdomen ultrasound, and sezary cell test were advised for the patient. Such presentations at that age have not, to our knowledge, been documented before.
PubMed: 36628019
DOI: 10.7759/cureus.32303 -
Cancers Dec 2022Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is associated with a poor prognosis and severe symptoms.
BACKGROUND
Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is associated with a poor prognosis and severe symptoms.
OBJECTIVE
To establish insights into the quality of life (QoL), expectations, and treatment satisfaction of E-CTCL patients receiving mogamulizumab.
METHODS
Outcomes of this prospective cohort study conducted between September 2020 and August 2021 at the Leiden University Medical Center included the dermatology-specific QoL (Skindex-29), health-related QoL (RAND-12), degree of itch, pain, and fatigue (Visual Analogue Scale), patient's expectations, and treatment satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8)), measured at baseline and after six months.
RESULTS
13 patients with E-CTCL were included. Most patients anticipated a positive treatment effect on symptoms. Five patients (46%) improved one or more clinical categories regarding the symptoms domain, six (55%) regarding emotions, four (36%) regarding functioning, and four (36%) regarding the overall Skindex-29 score compared to baseline. The Mental Component Score clinically improved from 31 (IQR 29-51) at baseline to 38 (IQR 25-51). The median VAS itch improved significantly from baseline (8 (IQR 7-10) vs. 3 (IQR 1-8), = 0.024). Most patients (n = 7) were "very satisfied" with their treatment.
LIMITATIONS
There was a limited number of patients due to the rarity of the disease.
CONCLUSION
In general, mogamulizumab has a favorable effect on biochemical- and dermatology-specific QoL and physical functioning in some patients, with high treatment satisfaction. Itch especially improved over time in most patients. The treatment satisfaction was generally high. Mogamulizumab seems to be an effective treatment that improves the QoL in patients with E-CTCL.
PubMed: 36612028
DOI: 10.3390/cancers15010032 -
Blood Jan 2023
Topics: Humans; Adenosine; T-Lymphocytes; Sezary Syndrome; Adenosine Triphosphate; Skin Neoplasms; Immunosuppression Therapy
PubMed: 36602823
DOI: 10.1182/blood.2022018185 -
Actas Dermo-sifiliograficas Apr 2023Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its...
BACKGROUND AND OBJECTIVE
Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years.
PATIENTS AND METHODS
RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years.
RESULTS
Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]).
CONCLUSION
The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.
Topics: Male; Humans; Middle Aged; Female; Venereology; Dermatology; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Registries; Mycosis Fungoides
PubMed: 36529273
DOI: 10.1016/j.ad.2022.11.010 -
Cancer Feb 2023Risk factors for progression to advanced-stage mycosis fungoides (MF) are poorly defined.
BACKGROUND
Risk factors for progression to advanced-stage mycosis fungoides (MF) are poorly defined.
METHODS
The authors performed a single-center, retrospective cohort study among patients with MF at an academic medical center from 1990 to 2020 to identify clinical variables associated with progression to advanced-stage MF (stage IIB-IVB), and 388 patients who had a clinicopathologic diagnosis of early stage (IA-IIA) MF were identified from their cutaneous lymphoma database. Baseline clinical characteristics, laboratory values, imaging, and blood flow cytometry or T-cell receptor gene rearrangement (TCR) data were collected. Logistic regression was used to assess risk factors associated with progression.
RESULTS
Overall, 93 of 388 patients (24.0%) progressed to advanced stage. Patients who progressed had an increased risk of death (hazard ratio, 4.50; 95% CI, 2.89-7.00; p < .001). Progression was associated with a higher overall stage at diagnosis, tumor stage, lymph node stage, low-level blood involvement, as measured with TCR data and/or flow cytometry, and elevated lactate dehydrogenase (LDH). Limitations included missing data for LDH, imaging, peripheral blood TCR data, or flow cytometry assessed at diagnosis.
CONCLUSIONS
Staging and baseline laboratory assessments with imaging, peripheral blood flow cytometry, TCR data, and LDH in patients who have newly diagnosed MF may identify those who are at risk for progression to advanced stage.
Topics: Humans; Sezary Syndrome; Prognosis; Retrospective Studies; Neoplasm Staging; Mycosis Fungoides; Skin Neoplasms; Lymph Nodes; Receptors, Antigen, T-Cell
PubMed: 36523150
DOI: 10.1002/cncr.34579 -
Skin Therapy Letter Sep 2022Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US... (Review)
Review
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.
Topics: Humans; Photopheresis; Graft vs Host Disease; Dermatology; Lymphoma, T-Cell, Cutaneous; Scleroderma, Systemic; Skin Neoplasms
PubMed: 36469458
DOI: No ID Found -
Cancer Management and Research 2022Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical...
Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients' symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.
PubMed: 36444356
DOI: 10.2147/CMAR.S377015 -
Cells Nov 2022The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a "do-not-eat-me" sign preventing macrophagal phagocytosis... (Review)
Review
The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a "do-not-eat-me" sign preventing macrophagal phagocytosis via interaction with its ligand SIRPα. Malignant lymphocytes of mycosis fungoides and Sézary syndrome express CD47 highly, thus, being ideal candidates for targeted anti-CD47 therapies. The classes of current anti-CD47-SIRPα therapeutic molecules present in a large variety and include monoclonal antibodies against CD47 and SIRPα, bioengineered SIRPα proteins, miRNAs, and bispecific antibodies. We provided a detailed analysis of all available investigational drugs in a contest of cutaneous T-cell lymphoma. A combination of blockade of the CD47-SIRPα axis and secondary targets in the tumor microenvironment (TME) may improve the clinical efficacy of current immunotherapeutic approaches. We evaluated the possible combination and outlined the most promising one.
Topics: Humans; Phagocytosis; Lymphoma, T-Cell, Cutaneous; Macrophages; Antibodies, Bispecific; Skin Neoplasms; Tumor Microenvironment; CD47 Antigen
PubMed: 36429020
DOI: 10.3390/cells11223591