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Cells Mar 2024Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)-the most common variant of... (Review)
Review
Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)-the most common variant of CTCL-often presents with skin lesions around the abdomen and buttocks ("bathing suit" distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL.
Topics: Humans; Skin Neoplasms; Vitamin D; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Skin; Skin Diseases; Vitamins
PubMed: 38534347
DOI: 10.3390/cells13060503 -
Cureus Feb 2024Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma with a usually indolent course. Early detection is crucial for effective intervention. We...
Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma with a usually indolent course. Early detection is crucial for effective intervention. We present a case of a 40-year-old male with MF exhibiting blistering as a rare precursor symptom. Despite initial treatment for eczema, the condition worsened over 10 months, leading to erythema, edema, and enlarged lymph nodes. Laboratory and imaging findings confirmed the diagnosis of MF. The patient responded partially to cyclophosphamide/doxorubicin/prednisone in combination with brentuximab vedotin (A-CHP) therapy. This case highlights the significance of recognizing blistering as a prodromal symptom for early detection and management of MF.
PubMed: 38496187
DOI: 10.7759/cureus.54213 -
Blood Advances May 2024Sézary syndrome (SS) is an aggressive leukemic expansion of skin-derived malignant CD4+ T cells. Drug monotherapy often results in disease relapse because of the...
Sézary syndrome (SS) is an aggressive leukemic expansion of skin-derived malignant CD4+ T cells. Drug monotherapy often results in disease relapse because of the heterogenous nature of malignant CD4+ T cells, but how therapies can be optimally combined remains unclear because of limitations in understanding the disease pathogenesis. We identified immunologic transitions that interlink mycosis fungoides with SS using single-cell transcriptome analysis in parallel with high-throughput T-cell receptor sequencing. Nascent peripheral CD4+ T cells acquired a distinct profile of transcription factors and trafficking receptors that gave rise to antigenically mature Sézary cells. The emergence of malignant CD4+ T cells coincided with the accumulation of dysfunctional monocytes with impaired fragment crystallizable γ-dependent phagocytosis, decreased responsiveness to cytokine stimulation, and limited repertoire of intercellular interactions with Sézary cells. Type I interferon supplementation when combined with a monoclonal antibody targeting the chemokine receptor type 4 (CCR4), unleashed monocyte induced phagocytosis and eradication of Sézary cells in vitro. In turn, coadministration of interferon-α with the US Food and Drug Administration-approved anti-CCR4 antibody, mogamulizumab, in patients with SS induced marked depletion of peripheral malignant CD4+ T cells. Importantly, residual CD4+ T cells after Sézary cell ablation lacked any immunologic shifts. These findings collectively unveil an auxiliary role for augmenting monocytic activity during mogamulizumab therapy in the treatment of SS and underscore the importance of targeted combination therapy in this disease.
Topics: Humans; Sezary Syndrome; Monocytes; Interferon Type I; Receptors, CCR4; CD4-Positive T-Lymphocytes; Antibodies, Monoclonal, Humanized; Skin Neoplasms
PubMed: 38489234
DOI: 10.1182/bloodadvances.2023010043 -
Indian Journal of Cancer Mar 2024Recent studies indicate an upsurge of primary cutaneous lymphoma (PCL) in the Indian population. Of late, we too have come across varied presentations of PCL in...
BACKGROUND
Recent studies indicate an upsurge of primary cutaneous lymphoma (PCL) in the Indian population. Of late, we too have come across varied presentations of PCL in relatively younger individuals. Hence, we decided to study the clinical and immunohistological profile of patients with PCL in our department.
METHODS
All cases diagnosed as PCL from October 2016 to October 2019 were included. Clinical details, complete blood count, peripheral smear, imaging, histopathology, and immunohistochemistry of skin specimens were analyzed. Lymph node biopsy and bone marrow studies were done in most cases. Human T lymphotropic virus-1 (HTLV1) serology was done in 10 cases.
RESULTS
Of the 24 patients with PCL, 12 were below 50 years of age. Twenty-three patients (95.8%) had T-cell lymphoma and only one had B-cell PCL. Mycosis fungoides (MF) (n = 17; 71%) was the most common type of PCL. There were two (8.3%) cases each of adult T-cell lymphoma/leukemia (ATLL) and Sezary syndrome. MF had varied clinical morphology at presentation and variable clinical outcomes. Both cases of ATLL had features of immunosuppression in the form of infective dermatoses.
CONCLUSION
We observed an increased proportion of T-cell type of PCL, with the age of onset being relatively early. HTLV-1 positivity was noted in three out of the 10 cases tested. More studies are needed to determine the factors responsible for the younger age of onset of PCL and the role of HTLV-1 infection in the development of PCL.
PubMed: 38475892
DOI: 10.4103/ijc.ijc_841_21 -
Cells Feb 2024Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid...
Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage ( = 0.036) and lower levels of lactate dehydrogenase ( = 0.042). An increased percentage of cells positive for Tbet ( = 0.017), RORγT ( = 0.001), and PD-L1 ( = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.
Topics: Humans; Nuclear Receptor Subfamily 1, Group F, Member 3; Skin Neoplasms; B7-H1 Antigen; Up-Regulation; Programmed Cell Death 1 Receptor; Glia Maturation Factor; Mycosis Fungoides; Forkhead Transcription Factors
PubMed: 38474383
DOI: 10.3390/cells13050419 -
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 -
Cancers Feb 2024Little is known about the impact of MF on quality of life (QoL) in newly diagnosed patients.
BACKGROUND
Little is known about the impact of MF on quality of life (QoL) in newly diagnosed patients.
OBJECTIVES
To describe the impact of the MF diagnosis on QoL, patient expectations, and treatment satisfaction over the first 6 months after diagnosis.
METHODS
Outcomes of this prospective cohort study of newly diagnosed MF patients conducted between 2020 and 2022 at the Leiden University Medical Center included the Skindex-29, RAND-12 Health Survey, degree of itch, pain, and fatigue (Visual Analogue Scale (VAS)), patient expectations, and Client Satisfaction Questionnaire-8 (CSQ-8), measured at baseline and after six months.
RESULTS
A total of 28 patients with MF were included. At baseline, 66% (n = 18) "strongly-totally" expected positive effects of the treatment. At the time of diagnosis, 28% of the patients (n = 8) were moderately to severely affected. There was no statistical change in the Skindex-29 score sum score (20 [10-34] vs. 20 [9-36]; = 0.81) or in the other three subdomains, the RAND-12 scores, and the VAS itch, pain, and fatigue over time. Treatment satisfaction was high overall.
CONCLUSION
Despite that the newly diagnosed MF patients anticipate a positive treatment effect, few improvements in QoL and symptom reduction were found. These data can be used for adequate expectation management and provide a rationale for further evaluation of treatment regimens in these patients.
PubMed: 38473299
DOI: 10.3390/cancers16050937 -
Cancers Feb 2024Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation... (Review)
Review
Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.
PubMed: 38473222
DOI: 10.3390/cancers16050861 -
Bone Marrow Transplantation Jun 2024Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a...
Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a non-myeloablative allogeneic stem cell transplantation regimen consisting of total skin electron beam therapy, total lymphoid irradiation and antithymocyte globulin. Our prospective cohort consisted of 41 patients with a higher proportion of MF (34MF, 7SS). Acute GVHD Grade 2 to 4 was seen in 31.7% and chronic GVHD Grade 2 to 4 in 24%. The cumulative incidence of non-relapse mortality was 9.8% at 1 year and 12.6% at 2 years. At Day +90 post-transplant 66% of patients had a complete response (CR). With a median post-transplant follow up of 5.27 years, the 5-year overall survival rate was 37.7% (MF 36.7%, SS 57.1%). The 5-year cumulative incidence of progressive disease or relapse was 52.7% in all patients but only 20.8% in those with CR at transplant compared to 70.6% in those not in CR at transplant (p = 0.006). Long term survival is possible in advanced MF and SS with non-myeloablative transplantation and outcomes are improved in patients with CR at transplant.
Topics: Humans; Sezary Syndrome; Mycosis Fungoides; Male; Middle Aged; Female; Adult; Hematopoietic Stem Cell Transplantation; Antilymphocyte Serum; Aged; Transplantation, Homologous; Survival Rate; Prospective Studies; Allografts; Transplantation Conditioning; Graft vs Host Disease; Treatment Outcome
PubMed: 38472408
DOI: 10.1038/s41409-024-02236-z