China
Africa
Explore chapters and articles related to this topic
Cutaneous Lymphomas
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Emily Correia, Shalini Krishnasamy, Neda Nikbakht
Laboratory studies: The diagnosis requires the presence of Sezary cells in the peripheral blood; these cells are cerebriform and mononuclear. On complete blood count, a normal white blood cell count can be seen or there can be a moderate leukocytosis. In order to diagnose Sezary syndrome, there must be a Sezary cell count of at least 1000 cells per microliter. The buffy coat may also contain 15–30% Sezary cells.
Approach to Erythroderma
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
The International Society for Cutaneous Lymphomas has recognized variants of erythrodermic CTCL, which includes Sézary syndrome (SS), erythrodermic mycosis fungoides (lacks hematologic findings of SS), and erythrodermic CTCL, not otherwise specified [29]. Sézary syndrome is diagnosed by demonstration of a peripheral blood T-cell clone by molecular/cytogenetic methods: an expanded CD4+ population resulting in CD4:CD8 ratio >10%, absolute Sézary cell count of at least 1000 cells/mm3 and immunophenotypic abnormalities. Clinically it presents as intractable pruritus, erythroderma, and lymphadenopathy. Hematological involvement shows >5% atypical circulating lymphocytes [29]. The dermal infiltrate in Sézary syndrome mainly shows a T-helper-2 cytokine profile, whereas benign reactive erythroderma shows a T-helper-1 cytokine profile, indicating that, although clinically similar, they have different underlying pathogenic mechanisms [30,31]. Immunophenotype in Sézary syndrome is of a mature helper T cell with memory phenotype, viz., CD2, CD3, CD4, CD5, CD45R0+, and CD8–. CD4+ cells also lose the CD26 marker and when this CD26– subset exceeds 30% of CD4+ cells along with hematological involvement, a diagnosis of SS is made [32]. Two antigens P140 and SCS have been found in skin-infiltrating cells of patients with Sézary syndrome [32]. Resolution of the erythroderma can be seen with curative resection of the tumor, and its recurrence might indicate recurrence of the tumor. Absolute Sézary cell count and lymph node involvement are independent prognostic factors. In addition, development of skin tumors on a background of erythroderma, visceral involvement, advancing age, and presence of Ebstein-Barr virus genome in keratinocytes all have poor prognosis [32,33].
Single-cell RNA-sequencing reveals predictive features of response to pembrolizumab in Sézary syndrome
Published in OncoImmunology, 2022
Tianying Su, George E. Duran, Alexa C. Kwang, Nirasha Ramchurren, Steven P. Fling, Youn H. Kim, Michael S. Khodadoust
Treatment of T-cell malignancies with immune checkpoint inhibitors presents a theoretic risk of disease hyperprogression through release of T-cell inhibition. Examples of hyperprogression with PD-1 treatment have been observed in adult T-cell leukemia and peripheral T-cell lymphomas26,27 and stimulation of leukemic CTCL with nivolumab increases malignant T-cell proliferation ex vivo.28 To further evaluate the effect of pembrolizumab on Sézary cell proliferation, alterations in the cell cycle after three weeks of treatment were computationally inferred for Sézary cells. The percentage of Sézary cells in the more proliferative phases of the cell cycle (G2M and S) decreased significantly for responders while no significant change was observed for the non-responders (Figure 2i).
Novel therapeutic approaches for cutaneous T cell lymphomas
Published in Expert Review of Clinical Immunology, 2021
Antreas Pavlidis, Christina Piperi, Evangelia Papadavid
SS is more aggressive than MF and presents a five year OS of 26% with a median survival ~3 years [7]. It is defined by erythroderma and lymphadenopathy and characterized by atypical malignant Sézary cells with a central memory T cell phenotype, different from MF, in blood, lymph nodes and skin. However, SS also expresses TFH phenotype markers PD-1, ICOS, CXCL-13, Bcl-6 and CD10 [16,17]. The International Society for Cutaneous Lymphoma (ISCL) has recommended an absolute Sézary cell count of at least 1000 cells/μL for SS diagnosis [20]. The molecular profile of SS exhibits chromosomal aberrations which include gains in chromosomes on 8q24.3 and 17q and deletions on 10q and 17p [21]. Alterations have been described in many genes including PTEN, c-MYC, TP53, CDKN2A, MAP3K8, FAS, NKKB2, MAP2K3 FGFR2, DMBT1, ZEB1 [19,21]. In this review, we have performed a literature search of peer-reviewed articles on the PubMed and Web of Science using the terms ‘cutaneous T cell lymphoma’ or ‘mycosis fungoides’ or ‘Sézary syndrome’ and ‘systemic treatment’ published the last 15 years, until November 2020. Upon selection of all relevant original articles, we provide an update on the molecular and the immunological aspects of CTCL with special focus on MF and SS and discuss novel therapeutic agents with promising outcome.
Mogamulizumab in the treatment of advanced mycosis fungoides and Sézary syndrome: safety and efficacy
Published in Expert Review of Anticancer Therapy, 2020
Daniel J. Lewis, Alain H. Rook
Mogamulizumab is a novel targeted therapy that has improved the current treatment landscape for advanced MF/SS since its approval by the FDA in 2018. Although its response rate of 28% in the pivotal MAVORIC trial is similar to that of alternative agents for advanced disease, many of these agents were studied in smaller trials with different study populations [3–5,49]. For example, romidepsin is used to treat MF/SS primarily based on the results of a smaller phase II trial [4]. Moreover, brentuximab vedotin was studied in the phase III ALCANZA trial, which excluded patients with high Sézary cell counts and included patients with primary cutaneous anaplastic large-cell lymphoma [4,49]. Conversely, the phase III MAVORIC trial enrolled a significant proportion of patients with advanced or relapsed/refractory disease and also represents the largest randomized controlled trial in CTCL to date [18]. Mogamulizumab also offers specific advantages over other therapies for advanced MF/SS: a prolonged duration of response, a high response rate within the blood compartment, and a favorable safety profile.