ABSTRACT
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
Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p = 0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p = 0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p = 0.013). Interpretation: Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. Funding: French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.
ABSTRACT
BACKGROUND: Primary cutaneous lymphomas (PCL) are rare skin tumors of lymphoproliferative neoplasms and belong to the heterogeneous group of non-Hodgkin's lymphomas. PCL encompass a broad spectrum of clinical and histologic manifestations, with cutaneous T-cell lymphoma (CTCL) being the most common (73%). Due to the rarity of the diseases, population-based studies of care and epidemiology are limited. PATIENTS AND METHODS: Based on anonymized, age- and sex-adjusted SHI (statutory health insurance) claims data of approximately five million SHI-insured patients, a retrospective analysis was conducted over a six-year period (2012-2017) to determine the prevalence, incidence, and lethality in patients with mature-cell T/NK-cell lymphoma in Germany. RESULTS: A total of 1,336 patients with T-cell lymphoma were identified during the observation period. The six-year prevalence ranged from 27.35 to 43.58 per 100,000. Patients were 65% male with a mean age of 66 years (SD 15). There were 246 patients (approx. 20%) who died within the 6 years, up to 7% per year. The calculated incidence in 153 identified patients in 2017 is 3.65 to 3.92 per 100,000. CONCLUSIONS: For the first time, valid epidemiologic findings of patients with mature T-cell and NK-cell lymphomas were obtained using SHI claims data in Germany. Further analyses are needed to gain a deeper insight into the healthcare reality of patients with this rare disease.
Subject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Sezary Syndrome , Skin Neoplasms , Humans , Male , Aged , Female , Cross-Sectional Studies , Retrospective Studies , Lymphoma, T-Cell, Cutaneous/epidemiology , Lymphoma, T-Cell, Cutaneous/pathology , Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Germany/epidemiology , Mycosis Fungoides/pathologyABSTRACT
Despite increasing availability of therapies, patients with Sezary syndrome (SS) commonly endure multi-line treatment journeys, mostly with partial responses of short duration. Measuring clinical benefit is challenging; time-to-next-treatment (TTNT) provides a robust, objective measurement of efficacy. This international observational study examines patterns of clinical care and therapeutic benefit as measured by TTNT. TTNT was calculated for monotherapies and combination therapies, with consideration to treatment line. 178 patients with SS (73% de novo, 27% secondary) were included, receiving 721 lines of systemic therapy, with median follow-up of 56.9 months. Across all lines, 58 different therapeutic regimens were prescribed (54 were systemic therapies) and classified into 17 treatment groups. The most common first-line treatments were extracorporeal photopheresis (ECP)-containing combination therapy (20%) and retinoid monotherapy (19%). Median TTNT for all first-line therapies was short (5.4 months). First-line, combination therapies had longer median TTNT than monotherapies, 10.0 vs 5.0 months (P = .004), respectively. Later delivery of combination therapies was associated with shorter clinical benefit, with median TTNT reduced to 6.2 and 2.2 months for mid-line (2nd-4th line) and late-line (≥5th line), respectively (P < .001). First-line ECP-containing treatments were associated with longer median TTNT than non-ECP-containing treatments, 9.0 vs 4.9 months (P = .007). For both ECP-monotherapy and ECP-containing combination therapy, significant reductions in TTNT were seen in later lines. These data suggest therapeutic benefit from first-line delivery of combination therapy for SS and favor early inclusion of ECP in the treatment algorithm for those who can access it.
Subject(s)
Photopheresis , Sezary Syndrome , Skin Neoplasms , Humans , Sezary Syndrome/drug therapy , Skin Neoplasms/drug therapy , Treatment Outcome , Combined Modality TherapySubject(s)
Prurigo , Transcriptome , Humans , Prurigo/genetics , Gene Expression Profiling , Sequence Analysis, RNA , T-LymphocytesSubject(s)
Lymphoma, T-Cell, Cutaneous , Skin Neoplasms , Humans , Lymphoma, T-Cell, Cutaneous/genetics , Lymphoma, T-Cell, Cutaneous/pathology , Skin/pathology , Administration, Cutaneous , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Sequence Analysis, RNA , Tumor Microenvironment/geneticsABSTRACT
Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary cutaneous lymphoma. In about 25% of patients with mycosis fungoides, the disease may progress to higher stages. The pathogenesis and risk factors of progression in mycosis fungoides and Sézary syndrome are not yet fully understood. Previous works have investigated inter- and intrapatient tumor cell heterogeneity. Here, we overview the role of the tumor microenvironment of mycosis fungoides and Sézary syndrome by describing its key components and functions. Emphasis is put on the role of the microenvironment in promoting tumor growth or antitumor immune response, as well as possible therapeutic targets. We focus on recent advances in the field and point out treatment-related alterations of the microenvironment. Deciphering the tumor microenvironment may help to develop strategies that lead to long-term disease control and cure.
ABSTRACT
Our research group developed a novel nano-pitted (NP) TiO2 surface on grade 2 titanium that showed good mechanical, osteogenic, and antibacterial properties; however, it showed weak hydrophilicity. Our objective was to develop a surface treatment method to enhance the hydrophilicity of the NP TiO2 surface without the destruction of the nano-topography. The effects of dilute and concentrated orthophosphoric (H3PO4) and nitric acids were investigated on wettability using contact angle measurement. Optical profilometry and atomic force microscopy were used for surface roughness measurement. The chemical composition of the TiO2 surface and the oxidation state of Ti was investigated using X-ray photoelectron spectroscopy. The ccH3PO4 treatment significantly increased the wettability of the NP TiO2 surfaces (30°) compared to the untreated control (88°). The quantity of the absorbed phosphorus significantly increased following ccH3PO4 treatment compared to the control and caused the oxidation state of titanium to decrease (Ti4+ â Ti3+). Owing to its simplicity and robustness the presented surface treatment method may be utilized in the industrial-scale manufacturing of titanium implants.
Subject(s)
Lymphoma, Large-Cell, Anaplastic , Mycosis Fungoides , Skin Neoplasms , Humans , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/pathology , Mycosis Fungoides/pathology , Antibodies, Monoclonal, Humanized/adverse effects , Skin Neoplasms/pathology , Ki-1 AntigenABSTRACT
The adsorption technique is widely used in water purification, and its efficiency can be significantly improved by target-specific adsorbent design. Research on iodine and its ion removal from water has attracted a great deal of interest due to increased concentrations in the environment and acute toxic effects, e.g., in human thyroid cells. In this work, the iodide removal performance of two high-surface-area resorcinol-formaldehyde-based carbon aerogels was studied under acidic conditions. The BET surface area was 790 m2/g (RF_ac) and 375 m2/g (RMF-GO), with a corresponding micropore ratio of 36 and 26%, respectively. Both aerogels showed outstanding adsorption capacity, exceeding the reported performance of other carbons and Ag-doped materials. Owing to its basic nature, the RMF-GO carbon aerogel showed higher I- capacity, up to 97 mg/g, than the acidic RF_ac, which reached a capacity of 82 mg/g. The surface chemistry of the aerogels also played a distinct role in the removal. In terms of kinetics, RF_ac removed 60% of the iodide ions and RMF-GO 30% within 8 h. The removal kinetics was of the first order, with a half-life of 1.94 and 1.70 h, respectively.
ABSTRACT
Primary cutaneous Tcell lymphomas are a heterogeneous group of rare diseases. Patients often suffer from visible, severely pruritic skin lesions, infections, relapses, and their life expectancy may be reduced. Under current therapies, long-lasting, complete remission is rare. However, new treatment approaches and combination therapies are changing the future. Here, we provide an overview on this topic.
Subject(s)
Lymphoma, T-Cell, Cutaneous , Skin Neoplasms , Combined Modality Therapy , Humans , Lymphoma, T-Cell, Cutaneous/therapy , Neoplasm Recurrence, Local , Remission Induction , Skin Neoplasms/drug therapySubject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Humans , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/therapy , Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Skin Neoplasms/pathology , Skin/pathology , PrognosisABSTRACT
BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) are rare forms of non-Hodgkin's lymphoma of T-cell origin that occur mainly in the skin. The most common form is mycosis fungoides (MF), but Sézary syndrome (SS), a more aggressive form of CTCL, is another relevant subgroup. Due to the rare nature of the disease, population-based studies of the epidemiology and disease burden and insights into care delivery are limited. PATIENTS AND METHODS: Based on an anonymized, age and sex-adjusted routine dataset comprising approximately five million people with statutory health insurance, a retrospective, longitudinal healthcare research study was conducted over a six-year period (2012-2017). RESULTS: In 55 % of patients with MF and SS, the initial diagnosis was documented in an outpatient setting; in 59 % of cases by a dermatologist. Immunophenotyping by flow cytometry is considered an important investigative tool for the detection and follow-up surveillance of blood involvement of cutaneous lymphomas, as the disease stage is the most important prognostic factor in MF and SS; this was performed in only 10 % of patients. The first-line treatment was topical (76 %), in particular with corticosteroids (66 %). CONCLUSIONS: The findings from this healthcare research point to the need for increased guideline-based care.