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Background: Primary cutaneous lymphomas are neoplasms of the immune system with a distinct tropism for the skin and an absence of extracutaneous manifestations at the time of diagnosis. Studies focusing on cutaneous lymphomas in children and adolescents remain scarce and often do not encompass the rare subtypes. Objectives: To address this knowledge gap by describing the clinical, histological and molecular characteristics of a large group of paediatric patients affected by primary cutaneous lymphoma. We also provided the Paediatric Primary Cutaneous Lymphoma Atlas that illustrates the clinicopathological spectrum of observed presentations, in the hope of supporting other physicians in the diagnostic process. Methods: Retrospective chart review of paediatric patients diagnosed with primary cutaneous lymphomas between 1980 and 2022 at the Paediatric Dermatology Unit of Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Milan. Results: A total of 101 patients (58 males, 43 females) met the inclusion criteria. The most common subtypes were lymphomatoid papulosis (n = 48) and mycosis fungoides (n = 31). These were followed by primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorders (n = 7), primary cutaneous anaplastic large‐cell lymphomas (n = 5), primary cutaneous marginal zone B‐cell lymphomas (n = 3), primary cutaneous follicle centre lymphomas (n = 2), subcutaneous panniculitis‐like T‐cell lymphomas (n = 2), primary cutaneous peripheral T‐cell lymphoma not otherwise specified (n = 1), primary cutaneous precursor B‐lymphoblastic lymphoma (n = 1) and Sézary syndrome (n = 1). Clinical follow‐up data covering a median of 70.8 months (range 1–324) were available for 74 patients, of whom three died due to cutaneous lymphoma. Conclusions: Our findings shed light on the peculiar aspects and long‐term outcomes of paediatric cutaneous lymphomas, particularly emphasizing their distinctive features in comparison to their adult counterparts and exploring the less common subtypes. Further larger‐scale studies are warranted to better characterize these entities and to achieve a more rapid and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cutaneous T cell lymphomas (CTCLs) are comprised of a heterogenous group of non-Hodgkin lymphomas that can be difficult to treat and are often refractory to standard therapies. Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes, accounting for the majority of CTCLs. There is no standard of care, and no treatments are curative. In this review, we summarize the promising, recently reported data describing novel systemic agents for the management of MF/SS. Recent Findings: Clinical trials are currently exploring a number of agents, including novel chemotherapies, antibodies and antibody drug conjugates (ADCs), immunotherapy, and cellular therapies. Summary: These promising novel agents may expand the treatment landscape for MF/SS. [ABSTRACT FROM AUTHOR]

The correction notice in the journal "Frontiers in Oncology" addresses errors in Table 1, Tables 2 and 3, and clarifies the presentation of domain scores and total scores in the educational needs assessment tool for patients with cutaneous lymphoma. The correction emphasizes the need for education, particularly regarding disease process and treatment, among patients, with statistical significance noted in certain domains. The authors acknowledge the errors and affirm that the scientific conclusions of the article remain unchanged. [Extracted from the article]

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs. Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023. Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, β2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival. Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS. [ABSTRACT FROM AUTHOR]

Peripheral blood involvement by MF/SS has significant implications for prognosis and treatment. Flow cytometry is commonly used to assess MF/SS by analyzing the ratio of CD26- and/or CD7-CD4 + T cells and assessment of immunophenotypic abnormalities. However, distinguishing normal from abnormal cells is not always easy. In this study, we aimed to establish quantitative thresholds to better distinguish normal CD4 + T cells from neoplastic CD4 + T cells. A retrospective analysis of flow cytometry data was performed on 30 MF/SS patients with a detectable abnormal T cell population (positive), 63 patients with suspected or confirmed cutaneous involvement without a detectable abnormal T cell population (negative), and 60 healthy controls (control). CD3 and CD4 median fluorescence intensity (MFI) was normalized to internal control subsets. Among the positive cases, 50% had CD3 expression outside ± 2 SD from the mean of the negative and control group in the CD4 + CD26- subset. The corresponding specificity of this threshold was 94%. The ± 2 SD threshold showed a sensitivity of 57% and a specificity of 94% for the CD3 intensity among the CD7-negative subset. For CD4 intensity, the ± 2 SD threshold had a sensitivity of 33.3% and specificity of 95% for the CD26-negative subset and a sensitivity of 37% and specificity of 95% for the CD7-negative subset. In our study, although changes in CD3 and CD4 intensity greater than ± 2 SD were specific for MF/SS, more subtle differences in the intensity of CD3 and CD4 should not be used as the sole abnormality to make a diagnosis of circulating MF/SS. [ABSTRACT FROM AUTHOR]

Introduction: Sézary syndrome (SS) is a rare leukemic cutaneous T cell lymphoma. This study was conducted to examine the real-world treatment patterns among patients with SS in the USA from 2018 to 2020. Methods: This was a retrospective cohort study using the Symphony Health Solutions claims database. Adult patients with ≥ 1 diagnosis code for SS were classified into three non-mutually exclusive cohorts: 2018, 2019, and 2020. Patient characteristics and treatment patterns were examined across the 3 years of study and reported descriptively for each year. Annual treatment patterns were also described for the five states with the highest proportions of SS patients in 2020. Results: Overall, 869, 882, and 853 SS patients were identified in 2018, 2019, and 2020, respectively (median age: 70 years for each year; male: 54.4%, 54.8%, and 55.6%, respectively). The use of any systemic and parenteral systemic treatments increased over time. While utilization rates for many specific systemic therapies decreased over the study period, mogamulizumab use increased, making it the most commonly used systemic treatment in 2020 (29.2%) among patients with any systemic treatment. The five states with the highest proportions of SS patients in 2020 were Florida, New York, California, Texas, and Pennsylvania. Systemic treatment patterns varied considerably by state. Conclusion: Some systemic therapies showed decreased usage over time while a few showed increased utilization, with mogamulizumab showing the largest increase. Treatment patterns for SS varied by region. Further research is needed to examine the factors that drive treatment selection for patients with SS. [ABSTRACT FROM AUTHOR]

Brentuximab vedotin (BV) has been approved for CD30‐positive cutaneous T‐cell lymphoma (CTCL) after at least one previous systemic treatment in China. However, real clinical practice is still limited. We aim to retrospectively review our experience with BV in a cohort of Chinese patients with CTCL, focusing on its efficacy and safety. We included 17 CTCL patients treated with BV at Peking Union Medical College Hospital from January 2021 to June 2024, including 12 with mycosis fungoides (MF)/Sézary syndrome (SS) and five with primary cutaneous anaplastic large‐cell lymphoma (pc‐ALCL). Patients had previously received a median of three treatment regimens (including acitretin, interferon, methotrexate, histone deacetylase inhibitors, phototherapy, radiotherapy, and chemotherapy). Sixteen patients received BV treatment at an initial dose of 1.8 mg/kg intravenously every 3 weeks, either as monotherapy (7/17) or in combination with gemcitabine, chidamide, or multiagent chemotherapy. The median treatment cycle has six cycles. Two patients received BV as the last treatment before undergoing allogeneic stem cell transplantation (alloSCT). The overall response rate (ORR) was 71% (13/17), with 18% (3/17) achieving complete remission (CR). In the MF/SS group, the ORR was 58% (7/12), while in the pc‐ALCL group, it was 100% (5/5). Adverse events (AEs) were observed in 12 patients, including peripheral neuropathy (PN) in three cases, fever in six cases, neutropenia in three cases, exfoliative dermatitis in two cases, and abnormal liver function in one case. Only one patient experienced ≥ Grade 3 AEs. Based on clinical experience in our center, BV, either as monotherapy or combined with chemotherapy, showed a good response in the treatment of advanced CTCL patients with good tolerability. [ABSTRACT FROM AUTHOR]

Summary: Traditionally, Sezary syndrome (SS) has been associated with few therapeutic options and poor prognosis, with 5‐year disease‐specific survival (DSS) less than one‐third in historical cohorts. However, newer therapies and combinations are associated with impressive time‐to‐next‐treatment (TTNT), particularly allogeneic stem‐cell transplantation (AlloSCT) and combination therapies notably those including extracorporeal photopheresis. In this multicentre, international study, we explored the prognostic outcomes of 178 patients exclusively managed for SS, diagnosed between 2012 and 2020, and treated in the modern therapeutic era. In this cohort, 58 different therapies were delivered, with 13.5% of patients receiving AlloSCT. Long‐term survival exceeded historical reports with 5‐year DSS and OS of 56.4% and 53.4% respectively. In those receiving AlloSCT, prognosis was excellent: 5‐year DSS and OS were 90.5% and 78.0% respectively. Confirming the results from the Cutaneous Lymphoma International Consortium (CLIC), LDH and LCT had significant prognostic impact. Unlike earlier studies, stage did not have prognostic impact; we speculate that greater relative benefit favours patients with extensive lymphomatous nodal disease (Stage IVA2) compared to historical reports. For patients ineligible for AlloSCT, the prognosis remains relatively poor (5‐year DSS 51.4% and OS 49.6%), representing ongoing unmet needs for more effective novel agents and investigation of improved therapeutic combinations. [ABSTRACT FROM AUTHOR]

Simple Summary: Precise analysis of T-cell receptor clonality is essential in lymphoma diagnostics, particularly for cutaneous T-cell lymphomas like Mycosis fungoides (MF) and Sézary Syndrome (SS). The current gold standard, based on next generation sequencing (NGS), is precise and accurate but time- and cost-intensive. This study established a workflow for the analysis of the T-cell receptor repertoire using third generation nanopore sequencing. Results are similarly accurate to NGS for cutaneous T-cell lymphoma, but less time-consuming and cost-intensive. Background: Analysis of T-cell receptor (TCR) clonality is a major diagnostic tool for lymphomas, particularly for cutaneous T-cell lymphomas (CTCL) like Mycosis fungoides and Sézary syndrome. However, a fast and cost-effective workflow is needed to enable widespread use of this method. Methods: We established a procedure for TCR rearrangement analysis via Oxford Nanopore Technology (ONT) sequencing. TCR receptor rearrangements (TCR-gamma and TCR-beta chains) were analyzed in samples from 45 patients with various diagnoses: Mycosis fungoides (37/45), Sézary Syndrome (2/45), folliculotropic CTCL (1/45), and non-CTCL diagnoses as polyclonal controls (5/45). Sample types included formalin-fixed paraffin-embedded (FFPE) samples (27/45), fresh frozen samples (9/45), and CD3-isolated cells (9/45). In addition, DNA of a Jurkat cell line was used as a monoclonal control. TCR amplicons were generated employing an optimized version of the protocol from the Euro Clonality consortium. Sequencing was conducted on the ONT GridION and Illumina MiSeq platforms, followed by similar bioinformatic analysis protocols. The tumor clone frequency (TCF), a crucial prognostic factor for CTCL patients, was used for method comparison. Results: The use of an optimized amplicon protocol and adapted bioinformatic tools demonstrated a strong correlation in TCF values between both sequencing methods across all sample types (range R: 0.992–0.996; range r2: 0.984–0.991). Conclusions: In summary, ONT sequencing was able to detect TCR clonality comparable to NGS, indicating its potential as a faster and more cost-effective option for routine diagnostic use. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background: Interferon‐alpha is an important therapeutic option for the treatment of the cutaneous T‐cell lymphomas (CTCL). Since the approved recombinant interferon‐α‐2a (IFN‐α2a) has no longer been produced since January 2020, pegylated interferon‐α2a (pegIFN‐α2a) can be used as an alternative treatment, even though it is not approved for the treatment of CTCL. The aim of this multicentre study was to generate comprehensive data on the efficacy and tolerability of pegIFN‐α2a in the treatment of CTCL. Patients and Methods: A multicenter retrospective study was conducted with 70 patients with CTCL from twelve German skin centers. Results: In total, 70 patients were included in the study, with 57.2% male and a mean age of 58.8 ± 14.9 years. Mycosis fungoides was present in 71.4% of cases and Sézary Syndrome in 28.6%. An overall response rate of 55.2% was observed with pegIFNα‐2a therapy. In 50% of cases, therapy was discontinued after 63.6 ± 33.5 weeks. The most common reason for discontinuation was adverse events, which occurred in 68.6% of cases and which were classified as severe in 29.2%. Blood count changes, fatigue and liver toxicity occurred most frequently. Conclusions: Our analysis provides comprehensive data on the efficacy and tolerability of pegIFNα‐2a therapy in patients with CTCL. In terms of response rates and side effect profile, pegIFNα‐2a appears to be comparable to IFN‐α2a therapy. [ABSTRACT FROM AUTHOR]

Copyright of Dermatologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Introduction Sézary syndrome (SS) is a rare leukemic cutaneous T cell lymphoma. This study was conducted to examine the real-world treatment patterns among patients with SS in the USA from 2018 to 2020. Methods This was a retrospective cohort study using the Symphony Health Solutions claims database. Adult patients with ≥ 1 diagnosis code for SS were classified into three non-mutually exclusive cohorts: 2018, 2019, and 2020. Patient characteristics and treatment patterns were examined across the 3 years of study and reported descriptively for each year. Annual treatment patterns were also described for the five states with the highest proportions of SS patients in 2020. Results Overall, 869, 882, and 853 SS patients were identified in 2018, 2019, and 2020, respectively (median age: 70 years for each year; male: 54.4%, 54.8%, and 55.6%, respectively). The use of any systemic and parenteral systemic treatments increased over time. While utilization rates for many specific systemic therapies decreased over the study period, mogamulizumab use increased, making it the most commonly used systemic treatment in 2020 (29.2%) among patients with any systemic treatment. The five states with the highest proportions of SS patients in 2020 were Florida, New York, California, Texas, and Pennsylvania. Systemic treatment patterns varied considerably by state. Conclusion Some systemic therapies showed decreased usage over time while a few showed increased utilization, with mogamulizumab showing the largest increase. Treatment patterns for SS varied by region. Further research is needed to examine the factors that drive treatment selection for patients with SS.

Patients with advanced-stage mycosis fungoides (MF IIB–IVB) and Sézary syndrome (SS) have poor prognoses, with survival ranging from 4.7 to 1.4 years depending on the disease stage. There is a need for therapeutic approaches that lead to long-lasting responses and improved quality of life and survival. Mogamulizumab, a humanized antibody against the CCR4 molecule, and low-dose total skin electron beam therapy (TSEBT) are two known established treatments for MF and SS as a monotherapy. However, little is known about the potential additive effect on the combination of both treatments. We report here for the first time the concurrent use of low-dose hypofractionated TSEBT (2 × 4 Gy) with mogamulizumab. Based on two relapsed/refractory and advanced-stage CTCL patients, we show that this combination may be well tolerated in advanced-stage MF or SS and may potentially lead to an additive treatment effect on response times, particularly in the skin and blood within two weeks. We propose that this combination may be a treatment option for patients with SS. Further research is needed to understand the efficacy and tolerability profile of this therapeutic combination and to determine if there is an additive effect of the combination on the response rates when compared with the monotherapy.