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1
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Özistanbullu D, Wilhelm R, Reichenbach G, Doll M, Bahrami K, Zöller N, Schnütgen F, König A, Scheller T, Winkler L, Spahn P, Jäger M, Nicolay JP, Pfeilschifter J, Schilling B, Kaufmann R, Koch A, Kippenberger S, Kleemann J, Meissner M. Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma. Blood Adv 2025; 9:2651-2662. [PMID: 40020159 DOI: 10.1182/bloodadvances.2024015132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/02/2025] [Indexed: 05/29/2025] Open
Abstract
ABSTRACT Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durable therapies. Similar to other non-Hodgkin lymphomas (NHLs), MF and SS have a greater incidence rate in males than females. The endocrine contribution to this sex difference is unknown. Although several studies could show a potential role of estrogen receptor β (ERβ) on NHL lymphomagenesis, its impact on CTCL development is unknown. In this study, we investigated LY500307, a selective ERβ agonist, as a potential treatment for CTCL. Our results show that LY500307 selectively reduced the viability of CTCL cells, sparing noncancerous skin cells. Liquid chromatography with tandem mass spectrometry analysis revealed that CTCL cells accumulated significantly higher concentrations of LY500307 than normal skin cells, likely contributing to its selective cytotoxicity. Mechanistically, LY500307 induced apoptosis, G2/M cell cycle arrest, and increased sensitivity to chemotherapeutic agents, particularly Monomethyl auristatin E. Furthermore, LY500307 treatment significantly reduced tumor growth in a CTCL xenograft mouse model without notable toxicity. These findings suggest LY500307 as a promising therapeutic agent for CTCL, warranting further clinical investigation, including the potential for topical applications.
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Affiliation(s)
- Deniz Özistanbullu
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Raphael Wilhelm
- Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
- Department of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt, Germany
| | - Gabi Reichenbach
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Monika Doll
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Karola Bahrami
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Nadja Zöller
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Frank Schnütgen
- Department of Molecular Hematology and LOEWE Center for Cell and Gene Therapy, Goethe University Medical School, Frankfurt, Germany
| | - Anke König
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Theresia Scheller
- Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin, Germany
| | - Lars Winkler
- Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin, Germany
| | - Pascal Spahn
- Department of Dermatology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
| | - Manuel Jäger
- Department of Dermatology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
| | - Jan P Nicolay
- Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
| | - Josef Pfeilschifter
- Department of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt, Germany
| | - Bastian Schilling
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Roland Kaufmann
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Alexander Koch
- Department of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt, Germany
| | - Stefan Kippenberger
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Johannes Kleemann
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Markus Meissner
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
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2
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Kołkowski K, Sławińska M, Zagórska B, Nowicki RJ, Jankau J, Sokołowska-Wojdyło M. Scalp Involvement in Primary Cutaneous Lymphomas-An Update on Clinical Presentation, Diagnostics, and Management. Cancers (Basel) 2025; 17:1678. [PMID: 40427175 PMCID: PMC12110331 DOI: 10.3390/cancers17101678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 05/05/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
Primary cutaneous lymphomas (PCLs) constitute a heterogeneous group of rare diseases. Previously, few studies have focused on the aspect of scalp involvement by PCLs. The objective of this study was to analyze the clinical presentation, diagnostic pathways, and treatment methods in patients diagnosed with scalp PCLs. A comprehensive literature review was conducted using the PubMed database, with the search terms "scalp" AND "cutaneous lymphoma", "folliculotropic mycosis fungoides" AND "scalp", "trichoscopy" AND "lymphoma", and "dermoscopy" AND "scalp" AND "lymphoma." The search was limited to articles published from database inception to May 2, 2024. Based on the title and abstract analysis, we included articles on PCLs involving the scalp. After a thorough review of the full manuscripts, several were excluded due to irrelevance, the absence of essential clinical data, discrepancies in patient age, gender, and diagnosis, and a lack of information pertinent to scalp PCLs. The literature search identified 1482 patients with scalp involvement in PCLs. Of the total number of cases, 1096 were diagnosed with B-cell PCLs, 384 with T-cell PCLs, and two cases lacked a precise PCL diagnosis. Primary cutaneous follicle center lymphoma was the most frequently reported B-cell PCL of the scalp, while mycosis fungoides was the most common T-cell PCL. Alopecia was observed in 69.0% of the patients analyzed, with the most prevalent form being non-scarring focal alopecia. It is imperative to consider the scalp in patients with PCLs, particularly in light of the knowledge that some lymphomas affecting the scalp exhibit a higher degree of aggressiveness.
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Affiliation(s)
- Karol Kołkowski
- Department of Dermatology, Venereology and Allergology, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland; (M.S.); (B.Z.); (R.J.N.); (M.S.-W.)
- Department of Plastic Surgery, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland;
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
- Department of Plastic Surgery, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
| | - Martyna Sławińska
- Department of Dermatology, Venereology and Allergology, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland; (M.S.); (B.Z.); (R.J.N.); (M.S.-W.)
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
| | - Beata Zagórska
- Department of Dermatology, Venereology and Allergology, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland; (M.S.); (B.Z.); (R.J.N.); (M.S.-W.)
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
| | - Roman J. Nowicki
- Department of Dermatology, Venereology and Allergology, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland; (M.S.); (B.Z.); (R.J.N.); (M.S.-W.)
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
| | - Jerzy Jankau
- Department of Plastic Surgery, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland;
- Department of Plastic Surgery, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
| | - Małgorzata Sokołowska-Wojdyło
- Department of Dermatology, Venereology and Allergology, University Clinical Centre, Smoluchowskiego 17 str., 80-214 Gdansk, Poland; (M.S.); (B.Z.); (R.J.N.); (M.S.-W.)
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Smoluchowskiego 17 str., 80-214 Gdansk, Poland
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Ortiz Romero PL, Kim YH, Molloy K, Quaglino P, Scarisbrick J, Thornton S, Sandilands K, Dent JE, Nixon A, Williams A, Shinohara MM. Health-related quality of life in cutaneous T-cell lymphoma: A post hoc analysis of a phase 3 trial in mycosis fungoides and Sézary syndrome. J Eur Acad Dermatol Venereol 2025; 39:833-845. [PMID: 39315857 PMCID: PMC11934017 DOI: 10.1111/jdv.20357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 09/06/2024] [Indexed: 09/25/2024]
Abstract
BACKGROUND Mycosis fungoides (MF) and Sézary syndrome (SS) are common subtypes of cutaneous T-cell lymphoma that primarily affect the skin but may spread to the lymph nodes, viscera and blood. The symptom burden may compromise health-related quality of life (HRQL). The phase 3 MAVORIC study (ClinicalTrials.gov identifier NCT01728805) in patients with relapsed/refractory MF/SS reported improved HRQL with mogamulizumab compared with vorinostat. OBJECTIVES Use baseline (pre-treatment) data from the MAVORIC study to describe the symptom burden of MF/SS and identify characteristics associated with worse HRQL. METHODS Data were from 372 adults with stage IB-IVB histologically confirmed relapsed/ refractory MF or SS. Associations between demographic and medical history variables and worse HRQL (Skindex-29, ItchyQol and Functional Assessment of Cancer Therapy - General [FACT-G]) were determined by regression models. RESULTS In the cohort of 372 adults, 70% were white; 42% were female; mean age was 63 (SD 13.0) years. Fifty-five per cent had MF and 45% had SS; 77% had advanced (stage IIB-IV) disease, involving the skin in all patients and the blood and/or nodes in 66%. HRQL scores showed impairment versus normative means (where available), with the greatest impact on Symptoms and Emotions in the Skindex-29, Functioning in the ItchyQol, and Functional Wellbeing in the FACT-G. In regression analysis, worse HRQL across all domains and total score was associated with being female and younger, worse mSWAT score and worse itch for the Skindex-29 (n = 352), and being female, younger, Black/African American, worse performance status and worse itch for the ItchyQol (n = 369). Associations across domains and total score were not found for the FACT-G. Associations between domains and demographic/medical history were seen for all instruments. CONCLUSIONS The symptoms of advanced MF/SS compromise all HRQL domains. Treatment goals and therapeutic choice should be informed by individual patients' disease burden.
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Affiliation(s)
| | - Y. H. Kim
- Stanford University School of Medicine and Cancer InstituteStanfordCAUSA
| | - K. Molloy
- Tallaght University Hospital/Trinity College DublinDublinIreland
| | | | | | - S. Thornton
- Susan Thornton, Cutaneous Lymphoma FoundationPhiladelphiaPAUSA
| | | | | | | | | | - M. M. Shinohara
- University of Washington and Fred Hutchinson Cancer CenterSeattleWAUSA
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Nenonen J, Winther AH, Jonsson P, Ivert LU, Brauner H. Identification of subgroups of early-stage mycosis fungoides patients with increased itch and impaired quality of life. Front Oncol 2025; 15:1524353. [PMID: 40094017 PMCID: PMC11906425 DOI: 10.3389/fonc.2025.1524353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/24/2025] [Indexed: 03/19/2025] Open
Abstract
Introduction Mycosis fungoides (MF), Sézary syndrome (SS) and other cutaneous T-cell lymphomas (CTCLs) can have a severe impact on quality of life (QoL) and itch, but early MF is insufficiently investigated despite representing most patients. This single center study investigated associations between QoL/itch/depressive symptoms and clinical phenotypes in patients with CTCL with particular focus on early MF-stages. Methods Patients were included during routine dermatological care. The primary outcomes included Dermatology Life Quality Index (DLQI), EuroQoL 5D (EQ-5D) index, Montgomery-Åsberg Depression Rating Scale - Self report (MADRS-S), and itch measured with a visual analogue scale (VAS-itch). Results In the total CTCL cohort (n=76), median EQ-5D index was impaired in female vs male patients (0.73 vs 0.85, p = 0.040). Among early MF patients (n=58), increased disease activity correlated with impaired DLQI (r = 0.413, p = 0.0014) and EQ-5D index (r = -0.317, p = 0.0161). Early MF patients with plaques vs only patches reported impaired EQ-5D index (median 0.725 vs 0.848, p = 0.0032) and increased itch (median VAS 3.27 vs 0.43, p = 0.0006). MF patients with stage IB vs IA reported impaired DLQI (median 5.00 vs 1.00, p = 0.0006), impaired EQ-5D index (median 0.725 vs 0.848, p = 0.0040) and increased itch (median VAS 3.37 vs 0.54, p = 0.0487). Discussion Although early MF patients reported generally a mild impact on QoL, this study highlights the need for disease management optimization for subgroups of early MF patients, including those with plaques, stage IB and higher disease activity.
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Affiliation(s)
- Julia Nenonen
- Division of Dermato-Venerology, Department of Medicine, Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Anna H Winther
- Division of Dermato-Venerology, Department of Medicine, Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden
| | - Pontus Jonsson
- Division of Dermato-Venerology, Department of Medicine, Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden
| | - Lina U Ivert
- Division of Dermato-Venerology, Department of Medicine, Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden
| | - Hanna Brauner
- Division of Dermato-Venerology, Department of Medicine, Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden
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Dirix M, Baart H, Neyens L, Dieu M, Stuyven C, Busschots AM, Woei-A-Jin FJSH. Improving quality of life in cutaneous lymphoma patients. J Eur Acad Dermatol Venereol 2025; 39:e195-e197. [PMID: 38923680 DOI: 10.1111/jdv.20207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024]
Affiliation(s)
- M Dirix
- Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - H Baart
- Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - L Neyens
- Department of Psychiatry, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - M Dieu
- Oncology Zone, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - C Stuyven
- Oncology Zone, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - A M Busschots
- Department of Dermatology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - F J S H Woei-A-Jin
- Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
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Raymundo C, Cella D, Wagner LI, Hippe DS, Di M, Guitart J, Rosen ST, Querfeld C, Shinohara MM. Development and psychometric properties of the Functional Assessment of Cancer Therapy-Cutaneous T-Cell Lymphoma (FACT-CTCL) instrument. Br J Dermatol 2024; 192:78-84. [PMID: 39078947 DOI: 10.1093/bjd/ljae308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 07/24/2024] [Accepted: 07/24/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Patients with mycosis fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL). OBJECTIVES To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy-General (FACT-G), in patients with MF/SS. METHODS Qualitative interviews were conducted with expert clinicians and patients with MF/SS. Thematic analysis identified the most common concerns, and 19 items were selected. Patients with MF/SS were recruited from a single centre. FACT-G, CTCL-S (collectively 'FACT-CTCL'), Skindex-29 and Visual Analogue Scale-Pruritis (VAS-itch) were administered. A subset repeated FACT-CTCL and VAS-itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical records. Psychometric properties were assessed. Internal consistency was estimated using Cronbach's α. Convergent and discriminant validity were assessed by comparing CTCL-S with disease stage, age, VAS-itch, FACT-G and Skindex-29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation and within-subject coefficient of variation. RESULTS Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS-itch after ≈2 weeks. Two-thirds were men; most were White (78%). The majority (85%) had MF, 15% had SS and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high, with α = 0.95 [95% confidence interval (CI) 0.93-0.96]. There was no significant change in CTCL-S average test-retest scores [ICC 0.93 (P = 0.63)]. CTCL-S was significantly lower in advanced vs. early-stage disease [median (interquartile range) 34 (26-48) vs. 59 (44-68), P < 0.001] and strongly correlated with VAS-itch [Spearman's r (rs) -0.70, 95% CI -0.81 to -0.55], FACT-G (rs 0.77, 95% CI 0.65-0.85) and Skindex-29 (rs -0.90, 95% CI -0.94 to -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs 0.19, 95% CI -0.05 to 0.41, P = 0.12), supporting discriminant validity. CONCLUSIONS The FACT-CTCL is a disease-specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.
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Affiliation(s)
| | - David Cella
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Lynne I Wagner
- Department of Health Policy and Management, University of North Carolina, Chapel Hill, NC, USA
| | | | - Mengyang Di
- Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Joan Guitart
- Northwestern University Department of Dermatology, Chicago, IL, USA
| | - Steven T Rosen
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA
| | - Christiane Querfeld
- Division of Dermatology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA
| | - Michi M Shinohara
- Fred Hutchinson Cancer Center, Seattle, WA, USA
- University of Washington Department of Dermatology, Seattle, WA, USA
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7
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Nagshabandi KN, Shadid A, Shadid A, Almuhanna NK. CD4/CD8 double-negative mycosis fungoides: a review. Dermatol Reports 2024; 16:9908. [PMID: 39669878 PMCID: PMC11632450 DOI: 10.4081/dr.2024.9908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/15/2023] [Indexed: 12/14/2024] Open
Abstract
Mycosis fungoides (MF) stands as the predominant form of primary cutaneous T-cell lymphoma (CTCL). It manifests a diverse array of clinical, histological, and immunophenotypic variations, each bearing distinct prognostic implications. The typical immunophenotypic profile of mycosis fungoides involves CD3+/CD4+/CD45RO+ memory T cells. Notably, the CD4-/CD8- double-negative variant of MF is a rare occurrence, observed in approximately 12% of early-stage cases and more prevalent in tumor-stage instances, often correlated with atypical clinical presentations. Despite its rarity, scant information is available about double-negative mycosis fungoides, with only a limited number of cases documented in the existing literature. This review aims to provide enhanced clarity, comprehension, and a detailed exploration of the spectrum encompassing double-negative mycosis fungoides.
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Affiliation(s)
| | | | - Asem Shadid
- Department of Dermatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Nouf K. Almuhanna
- Department of Dermatology, King Fahad Medical City, Riyadh, Saudi Arabia
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8
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Elsayad K, Guenova E, Assaf C, Nicolay JP, Trautinger F, Stadler R, Waldstein C, Boterberg T, Meijnders P, Kirova Y, Dobos G, Duque-Santana V, Riggenbach E, Elsheshtawy W, Niezink A, Papadavid E, Scarisbrick J, Vermeer M, Neelis KJ, Bagot M, Battistella M, Quaglino P, Knobler R, Kempf W, Maklad A, Adeberg S, Kouloulias V, Simontacchi G, Corradini S, König L, Eich HT, Cowan R, Correia D. Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group. Eur J Cancer 2024; 212:115064. [PMID: 39418694 DOI: 10.1016/j.ejca.2024.115064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/29/2024] [Accepted: 10/04/2024] [Indexed: 10/19/2024]
Abstract
The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.
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Affiliation(s)
- Khaled Elsayad
- Radiation Oncology, University Hospital of Münster, Münster, Germany; Department of Radiation Oncology, UKGM Marburg, Marburg, Germany; Marburg Ion-Beam Therapy Center (MIT), Department of Radiation Oncology, UKGM Marburg, Marburg, Germany; University Cancer Center (UCT) Frankfurt-Marburg, Marburg, Frankfurt, Germany.
| | - Emmanuella Guenova
- Department of Dermatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; University Institute and Clinic for Immunodermatology, Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Chalid Assaf
- Institute for Molecular Medicine, Medical School Hamburg, University of Applied Sciences and Medical University, Hamburg, Germany; Department of Dermatology, HELIOS Klinikum Krefeld, Krefeld, Germany, Medical School Hamburg, University of Applied Sciences and Medical University, Hamburg, Germany
| | - Jan P Nicolay
- Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany
| | - Franz Trautinger
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
| | - Rudolf Stadler
- Department of Dermatology, Johannes Wesling Medical Centre, University of Bochum, Minden, Germany
| | - Cora Waldstein
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University Vienna, Austria
| | - Tom Boterberg
- Department of Radiation Oncology, Ghent University Hospital, Belgium
| | - Paul Meijnders
- Iridium Netwerk, University of Antwerp, Antwerp, Belgium
| | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Hopital de Paris, France
| | - Gabor Dobos
- Department of Dermatology, Charite - Universitaetsmedizin Berlin - Campus Mitte, Germany
| | - Victor Duque-Santana
- Department of Radiation Oncology, Quironsalud Madrid University Hospital, Madrid, Spain; Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Spain
| | - Elena Riggenbach
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Wael Elsheshtawy
- Department of Clinical Oncology, Al Azhar University, Cairo, Egypt
| | - Anne Niezink
- Department of Radiation Oncology, University Medical Center Groningen, the Netherlands
| | - Evangelia Papadavid
- National and Kapodistrian University of Athens, 2nd Department of Dermatology and Venereology, Attikon General Hospital, University of Athens, Chaidari, Greece
| | - Julia Scarisbrick
- Department of Dermatology, University Hospital Birmingham, Birmingham, UK
| | - Maarten Vermeer
- Head of Department of Dermatology, Leiden University Medical Center, the Netherlands
| | - Karen J Neelis
- Department of radiotherapy, Leiden University Medical Center, the Netherlands
| | - Martine Bagot
- Department of Dermatology, Hopital Saint Louis, Université Paris Cité, INSERM U976, Paris, France
| | - Maxime Battistella
- APHP Department of Pathology, INSERM U976, University Paris Cité, Saint-Louis University Hospital, Paris, France
| | - Pietro Quaglino
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Robert Knobler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Werner Kempf
- Kempf und Pfaltz Histologische Diagnostik, Affolternstrasse 56, CH-8050 Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, CH-8091 Zurich, Switzerland
| | - Ahmed Maklad
- Department of Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Sebastian Adeberg
- Department of Radiation Oncology, UKGM Marburg, Marburg, Germany; Marburg Ion-Beam Therapy Center (MIT), Department of Radiation Oncology, UKGM Marburg, Marburg, Germany; University Cancer Center (UCT) Frankfurt-Marburg, Marburg, Frankfurt, Germany
| | - Vassilis Kouloulias
- Department of Radiation Oncology, National and Kapodistrian University of Athens, Athens, Greece
| | - Gabriele Simontacchi
- Department of Radiation Oncology, DAI Oncologia, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | | | - Laila König
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
| | - Hans Theodor Eich
- Radiation Oncology, University Hospital of Münster, Münster, Germany
| | - Richard Cowan
- Department of Clinical Oncology, Christie Hospital, University of Manchester, Manchester, United Kingdom
| | - Dora Correia
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Radiation Oncology, Cantonal Hospital Aarau, Aarau, Aargau, Switzerland
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9
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Brazel D, Larocca C, Shinohara MM. Assessing Health-Related Quality of Life in Mycosis Fungoides and Sézary Syndrome: Unmet Needs. Cancers (Basel) 2024; 16:2757. [PMID: 39123484 PMCID: PMC11312166 DOI: 10.3390/cancers16152757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) can impair multiple dimensions of health-related quality of life (HRQoL). Currently, there is no standardized assessment tool for measuring HRQoL in patients with MF/SS. Here, we describe the existing literature on multiple dimensions of HRQoL in MF/SS with a special focus on the gaps in the current knowledge and identify future directions necessary to assess the HRQoL of patients with this disease.
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Affiliation(s)
- Danielle Brazel
- Department of Hematology/Oncology, Scripps Clinic/Scripps Green Hospital, La Jolla, CA 92037, USA
| | - Cecilia Larocca
- Brigham and Women’s Department of Dermatology, Dana Farber Cancer Center, Boston, MA 02215, USA
| | - Michi M. Shinohara
- Department of Dermatology, University of Washington, 1959 Northeast Pacific Street BB-1353, Box 356524, Seattle, WA 98195, USA
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10
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Goel RR, Rook AH. Immunobiology and treatment of cutaneous T-cell lymphoma. Expert Rev Clin Immunol 2024; 20:985-996. [PMID: 38450476 DOI: 10.1080/1744666x.2024.2326035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/28/2024] [Indexed: 03/08/2024]
Abstract
INTRODUCTION Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders. AREAS COVERED In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome. EXPERT OPINION Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology.
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Affiliation(s)
- Rishi R Goel
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Institute for Immunology and Immune Health (I3H), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Alain H Rook
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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11
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Nielsen MH, Nielsen PR, Bzorek M, Eriksen JO, Wehkamp U, Lindahl LM, Woetmann A, Ødum N, Litman T, Gjerdrum LMR. Stage-related increase in PIM2 expression in mycosis fungoides. APMIS 2024; 132:564-570. [PMID: 38757234 DOI: 10.1111/apm.13423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 04/26/2024] [Indexed: 05/18/2024]
Abstract
The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). PIM2 is a well-known oncogene and is regulated by cell signaling pathways like the JAK/STAT- and NF-kB-pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin-fixed paraffin-embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced-stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced-stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID.
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Affiliation(s)
- Mie Holm Nielsen
- Department of Pathology, Copenhagen University Hospital - Zealand University Hospital Roskilde, Roskilde, Denmark
| | - Pia Rude Nielsen
- Department of Pathology, Copenhagen University Hospital - Zealand University Hospital Roskilde, Roskilde, Denmark
- Department of Immunology and Microbiology, LEO Foundation Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark
| | - Michael Bzorek
- Department of Pathology, Copenhagen University Hospital - Zealand University Hospital Roskilde, Roskilde, Denmark
| | - Jens Ole Eriksen
- Department of Pathology, Copenhagen University Hospital - Zealand University Hospital Roskilde, Roskilde, Denmark
| | - Ulrike Wehkamp
- Department of Dermatology, University Hospital, Kiel, Schleswig-Holstein, Germany
| | | | - Anders Woetmann
- Department of Immunology and Microbiology, LEO Foundation Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark
| | - Niels Ødum
- Department of Immunology and Microbiology, LEO Foundation Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Litman
- Department of Immunology and Microbiology, LEO Foundation Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark
| | - Lise Mette Rahbek Gjerdrum
- Department of Pathology, Copenhagen University Hospital - Zealand University Hospital Roskilde, Roskilde, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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12
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Qin Y, Lin Y, Chen Z, Zhang Q, Li Y, Wen Y, Tu P, Gao P, Wang Y. Effectiveness of narrowband ultraviolet B monotherapy versus combination therapy with systemic agents in patients with early-stage mycosis fungoides and the association with plaque lesions. J Evid Based Med 2024; 17:390-398. [PMID: 38898743 DOI: 10.1111/jebm.12623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024]
Abstract
OBJECTIVE Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects. METHODS This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model. RESULTS In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0% vs. 54.3%, p = 0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4 vs. 6 months, p = 0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed. CONCLUSIONS Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.
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Affiliation(s)
- Yao Qin
- Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
- National Clinical Research Center for Skin and Immune Diseases, Beijing, China
- NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Yuwei Lin
- Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China
| | - Zhuojing Chen
- Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
- National Clinical Research Center for Skin and Immune Diseases, Beijing, China
- NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Qiuli Zhang
- Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Yingyi Li
- Department of Dermatology, Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Yujie Wen
- Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
- National Clinical Research Center for Skin and Immune Diseases, Beijing, China
- NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Ping Tu
- Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
- National Clinical Research Center for Skin and Immune Diseases, Beijing, China
- NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Pei Gao
- Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Yang Wang
- Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
- National Clinical Research Center for Skin and Immune Diseases, Beijing, China
- NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
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13
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Bernard P, Guenova E. Decoding the impact of primary cutaneous B-cell lymphomas on patients' well-being. J Eur Acad Dermatol Venereol 2024; 38:794-795. [PMID: 38661027 DOI: 10.1111/jdv.19952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 03/04/2024] [Indexed: 04/26/2024]
Affiliation(s)
- Pauline Bernard
- Department of Dermatology, Lausanne University Hospital CHUV, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Emmanuella Guenova
- Department of Dermatology, Lausanne University Hospital CHUV, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
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14
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Schirren AEC, Albrecht JD, Melchers S, Weiß C, Büttner S, Dippel E, Gosmann J, Jonak C, Klemke CD, Laturnus-Chang M, Livingstone E, Mitteldorf C, Schummer P, Stadler R, Stranzenbach R, Weyer-Fahlbusch SS, Wobser M, Ziemer M, Nicolay JP. Health-related quality of life and its influencing factors in patients with primary cutaneous B-cell lymphomas: A multicentric study in 100 patients. J Eur Acad Dermatol Venereol 2024; 38:954-966. [PMID: 38279594 DOI: 10.1111/jdv.19799] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 12/11/2023] [Indexed: 01/28/2024]
Abstract
BACKGROUND Primary cutaneous B-cell lymphomas (CBCL) are a group of rare malignant skin diseases that represent approximately 20%-30% of all primary cutaneous lymphomas (PCL). Previous studies revealed impaired health-related quality of life (HRQoL) in patients diagnosed with primary cutaneous T-cell lymphoma (CTCL). Currently, only small-sized studies investigated HRQoL in CBCL patients and lacked detailed analysis of respective subtypes. OBJECTIVES This study aims to investigate HRQoL in CBCL patients to identify independent factors of HRQoL impairment in CBCL patients. METHODS One hundred CBCL patients were recruited from eight German PCL centres in this multicentric, cross-sectional study from 2021 to 2022. The patients completed the dermatologic HRQoL questionnaire Skindex-29 and an investigator-designed 'CBCL-Questionnaire' with additional questions on HRQoL and clinical characteristics. RESULTS The Skindex-29 revealed that HRQoL in CBCL patients is impaired on a mild to moderate level. The multiple regression analysis identified parameters like worries about dying, feeling prejudiced/discriminated and impairment of daily activities to be independently associated with impairment of HRQoL. Highest scores for HRQoL impairment were found in patients with primary cutaneous follicle centre lymphoma while on rituximab treatment and in patients with primary cutaneous marginal zone lymphoma while on watchful waiting. CONCLUSIONS HRQoL is impaired in CBCL patients, even though, in the face of indolent disease course and favourable prognosis in the majority of cases. Of note, our investigator-designed tool identified worries about dying, feeling prejudiced/discriminated, and the type of treatment to have a negative impact on patients' HRQoL. Our study highlights the importance of a thorough patient-doctor communication to capture overall disease burden because generic HRQoL tools might lack of disease-specific items.
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Affiliation(s)
- A E C Schirren
- Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Mannheim, Germany
- Section for Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - J D Albrecht
- Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Mannheim, Germany
- Section for Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Skin Cancer Unit, German Cancer Research Centre (DKFZ), Heidelberg, Germany
| | - S Melchers
- Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Mannheim, Germany
- Section for Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Skin Cancer Unit, German Cancer Research Centre (DKFZ), Heidelberg, Germany
| | - C Weiß
- Department for Medical Statistics, Biomathematics and Information Processing, Medical Faculty Mannheim of the University of Heidelberg and University Medical Centre Mannheim, Mannheim, Germany
| | - S Büttner
- Department for Medical Statistics, Biomathematics and Information Processing, Medical Faculty Mannheim of the University of Heidelberg and University Medical Centre Mannheim, Mannheim, Germany
| | - E Dippel
- Department of Dermatology, Ludwigshafen Medical Centre, Ludwigshafen, Germany
| | - J Gosmann
- University Clinic for Dermatology, Johannes Wesling Medical Centre, Minden, Germany
| | - C Jonak
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - C-D Klemke
- Department of Dermatology and Skin Cancer Centre, Municipal Hospital Karlsruhe, Academic Educational Hospital of the University of Freiburg, Karlsruhe, Germany
| | - M Laturnus-Chang
- Department of Dermatology, Ludwigshafen Medical Centre, Ludwigshafen, Germany
| | - E Livingstone
- Department of Dermatology, University Hospital Essen, Essen, Germany
| | - C Mitteldorf
- Department of Dermatology, Venereology and Allergology, University Medical Centre Göttingen, Göttingen, Germany
| | - P Schummer
- Department of Dermatology, University Hospital Würzburg, Würzburg, Germany
| | - R Stadler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - R Stranzenbach
- Department of Dermatology, Bochum Medical Centre, Bochum, Germany
| | | | - M Wobser
- Department of Dermatology, University Hospital Würzburg, Würzburg, Germany
| | - M Ziemer
- Department of Dermatology, University Medical Centre, Leipzig, Germany
| | - J P Nicolay
- Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Mannheim, Germany
- Section for Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Skin Cancer Unit, German Cancer Research Centre (DKFZ), Heidelberg, Germany
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15
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Porkert S, Griss J, Hudelist-Venz M, Steiner I, Valencak J, Weninger W, Brunner PM, Jonak C. Mortalität, prognostische Parameter und Behandlungsstrategien bei Mycosis fungoides. J Dtsch Dermatol Ges 2024; 22:532-552. [PMID: 38574037 DOI: 10.1111/ddg.15331_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 11/14/2023] [Indexed: 04/06/2024]
Abstract
ZusammenfassungHintergrund und ZieleMycosis fungoides (MF), das häufigste primär kutane T‐ Zell‐Lymphom, ist durch einen variablen klinischen Verlauf charakterisiert. Dieser ist entweder indolent oder infaust bei Progression mit extrakutaner Beteiligung. Das Fehlen von Prognosemodellen bei überwiegend palliativen Therapiemodalitäten erschweren das Patientenmanagement. Ziel dieser Studie war es, Überlebensraten, Treffsicherheit von verfügbaren Prognosemodellen und den Therapieerfolg bei MF‐Patienten zu evaluieren.Patienten und MethodikHundertvierzig MF‐Patienten wurden retrospektiv untersucht. Prognose, Krankheitsprogression beziehungsweise Überlebensraten wurden anhand univariater Cox‐ Regressionsmodellen und Kaplan‐Meier‐ Schätzungen analysiert.ErgebnisseHauttumoren waren im Vergleich zu Erythrodermie mit einem kürzeren progressionsfreien Überleben und Gesamtüberleben sowie einem 3,48‐fach erhöhtem Risiko für Krankheitsprogression verbunden. Der Cutaneous Lymphoma International Prognostic Index identifizierte Risikopatienten lediglich im frühen Krankheitsstadium. Zudem waren die Expression von Ki‐67 > 20%, CD30 > 10%, CD20+ und CD7– unabhängig vom Krankheitsstadium mit einem signifikant schlechteren Outcome verbunden. Eine langfristige Krankheitskontrolle wurde lediglich mit Interferon‐α als Monotherapie oder durch Kombination von Phototherapie mit Interferon‐α oder Retinoiden/Bexaroten erreicht.SchlussfolgerungenUnsere Daten unterstützen die Vorhersagekraft von etablierten Prognoseparametern und ‐modellen bei MF. Zusätzlich wurden neue Parameter, die mit einer schlechten Prognose assoziiert sind, identifiziert. Prospektive Studien, die Prognoseindikatoren in Bezug auf Krankheitsstadium und Therapie synergistisch evaluieren sind erforderlich, um die Patientenbetreuung zu verbessern.
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Affiliation(s)
- Stefanie Porkert
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | - Johannes Griss
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | | | - Irene Steiner
- Zentrum für Medizinische Statistik, Information und intelligente Systeme, Institut für Medizinische Statistik, Medizinische Universität Wien, Wien, Österreich
| | - Julia Valencak
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | - Wolfgang Weninger
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | - Patrick M Brunner
- Department of Dermatology, Icahn School of Medicineat Mount Sinai, New York, NY, USA
| | - Constanze Jonak
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
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16
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Porkert S, Griss J, Hudelist-Venz M, Steiner I, Valencak J, Weninger W, Brunner PM, Jonak C. Evaluation of mortality, prognostic parameters, and treatment efficacy in mycosis fungoides. J Dtsch Dermatol Ges 2024; 22:532-550. [PMID: 38444271 DOI: 10.1111/ddg.15331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 11/14/2023] [Indexed: 03/07/2024]
Abstract
BACKGROUND AND OBJECTIVES Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is characterized by a variable clinical course, presenting either as indolent disease or showing fatal progression due to extracutaneous involvement. Importantly, the lack of prognostic models and predominantly palliative therapy settings hamper patient care. Here, we aimed to define survival rates, disease prediction accuracy, and treatment impact in MF. PATIENTS AND METHODS Hundred-forty MF patients were assessed retrospectively. Prognosis and disease progression/survival were analyzed using univariate Cox proportional hazards regression model and Kaplan-Meier estimates. RESULTS Skin tumors were linked to shorter progression-free, overall survival and a 3.48 increased risk for disease progression when compared to erythroderma. The Cutaneous Lymphoma International Prognostic Index identified patients at risk in early-stage disease only. Moreover, expression of Ki-67 >20%, CD30 >10%, CD20+, and CD7- were associated with a significantly worse outcome independent of disease stage. Only single-agent interferon-α and phototherapy combined with interferon-α or retinoids/bexarotene achieved long-term disease control in MF. CONCLUSIONS Our data support predictive validity of prognostic factors and models in MF and identified further potential parameters associated with poor survival. Prospective studies on prognostic indices across disease stages and treatment modalities are needed to predict and improve survival.
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Affiliation(s)
- Stefanie Porkert
- Department of Dermatology, Medical University of Vienna, Viena, Austria
| | - Johannes Griss
- Department of Dermatology, Medical University of Vienna, Viena, Austria
| | - Mercedes Hudelist-Venz
- Department of Radiotherapy and Radiobiology, Medical University of Vienna, Viena, Austria
| | - Irene Steiner
- Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Viena, Austria
| | - Julia Valencak
- Department of Dermatology, Medical University of Vienna, Viena, Austria
| | - Wolfgang Weninger
- Department of Dermatology, Medical University of Vienna, Viena, Austria
| | - Patrick M Brunner
- Department of Dermatology, Icahn School of Medicineat Mount Sinai, New York, NY, USA
| | - Constanze Jonak
- Department of Dermatology, Medical University of Vienna, Viena, Austria
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17
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Ottevanger R, van Beugen S, Kersten JM, Evers AWM, Vermeer MH, Willemze R, Quint KD. Evaluation of Quality of Life and Treatment Satisfaction in Newly Diagnosed Cutaneous T-Cell Lymphoma Patients. Cancers (Basel) 2024; 16:937. [PMID: 38473299 DOI: 10.3390/cancers16050937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 02/20/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
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]; p = 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.
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Affiliation(s)
- Rosanne Ottevanger
- Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Sylvia van Beugen
- Health, Medical and Neuropsychology Unit, Institute of Psychology, Leiden University, 2311 EZ Leiden, The Netherlands
| | - Juliette M Kersten
- Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Andrea W M Evers
- Health, Medical and Neuropsychology Unit, Institute of Psychology, Leiden University, 2311 EZ Leiden, The Netherlands
| | - Maarten H Vermeer
- Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Koen D Quint
- Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
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18
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McFeely O, Walsh PM, Desmond R, Enright H, Costa Blasco M, Wolinska A, Murphy L, Andrawis M, Beatty P, Doyle C, Tobin AM, O'Gorman S, Molloy K. Incidence of cutaneous T-cell lymphoma in the Republic of Ireland between 1994 and 2019. J Eur Acad Dermatol Venereol 2024; 38:e145-e147. [PMID: 37705380 DOI: 10.1111/jdv.19497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 08/30/2023] [Indexed: 09/15/2023]
Affiliation(s)
- O McFeely
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - P M Walsh
- National Cancer Registry of Ireland, Cork, Ireland
| | - R Desmond
- Department of Haematology, Tallaght University Hospital, Dublin, Ireland
| | - H Enright
- Department of Haematology, Tallaght University Hospital, Dublin, Ireland
| | - M Costa Blasco
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - A Wolinska
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - L Murphy
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - M Andrawis
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - P Beatty
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - C Doyle
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - A M Tobin
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
| | - S O'Gorman
- Department of Dermatology, St. James's Hospital, Dublin, Ireland
| | - K Molloy
- Department of Dermatology, Tallaght University Hospital, Dublin, Ireland
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Ardigò M, Nikbakht N, Teoli M, Gleason L, Crisan L, Querfeld C. Chlormethine gel in combination with other therapies for treatment of mycosis fungoides: a review with patient cases. Front Med (Lausanne) 2024; 10:1308491. [PMID: 38274457 PMCID: PMC10810130 DOI: 10.3389/fmed.2023.1308491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 12/04/2023] [Indexed: 01/27/2024] Open
Abstract
Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients treated with chlormethine gel combined with phototherapy (n = 5), retinoids (n = 16), or mogamulizumab (n = 3) are presented. These different combination regimens showed promising results. Most patients had a complete or partial response following treatment and the combinations were well-tolerated over extended treatment periods. Patients receiving chlormethine gel with retinoids had long-term periods of remission, even after treatment discontinuation. Durations of response of up to 3 years were observed in these patients. This long-term disease control may be the result of disease-modifying effects of chlormethine. Previous studies have shown targeted reductions in malignant T-cell clones in patients treated with chlormethine gel as well as improved post-treatment responses. Further research is needed to determine the effectiveness and safety of combination treatment regimens with chlormethine gel and to assess the impact chlormethine gel has on disease control.
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Affiliation(s)
- Marco Ardigò
- Clinical Dermatology Department, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Neda Nikbakht
- Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, United States
| | - Miriam Teoli
- Clinical Dermatology Department, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Laura Gleason
- Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, United States
| | - Liliana Crisan
- Division of Dermatology and Department of Pathology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, United States
| | - Christiane Querfeld
- Division of Dermatology and Department of Pathology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, United States
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20
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Henderson Berg MH, Popradi G, Roberge D, Petrogiannis-Haliotis T, Pehr K. Psychological Distress and Treatment Outcome in Patients With Early-Stage Mycosis Fungoides. J Cutan Med Surg 2024; 28:29-32. [PMID: 38229268 PMCID: PMC10908191 DOI: 10.1177/12034754231220913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
BACKGROUND Skin diseases have been shown to worsen psychological distress, which, in turn, may be detrimental to treatment outcomes. Both the impact of psychological distress on response to treatment in mycosis fungoides (MF) and the effect of treatments on psychological well-being are unclear. OBJECTIVES To evaluate (1) the association between pretreatment psychological morbidity and treatment outcome in early-stage MF and (2) the impact of response to treatment on psychological well-being. METHODS This was a prospective cohort study of patients with early-stage MF who started a new stage-directed treatment for their disease. The response was determined using the modified severity-weighted assessment tool, and psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12) and Penn State Worry Questionnaire (PSWQ). Participants were followed for 1 year. RESULTS In all, 24 consecutive patients were recruited. Objective response rate was 71% (17/24), consistent with existing literature. Prior to treatment, 9 patients (38%) had clinically significant psychological distress on the GHQ-12, while 8 (33%) demonstrated high-level worry on the PSWQ. Of these patients, 6 had pathologic scores on both instruments. Patients with significantly less baseline anxiety/depression on the GHQ-12 responded better to treatment than patients with higher levels (P = .004). In addition, responders' mean GHQ-12 scores decreased by 39% and their PSWQ scores by 17%, whereas nonresponders' GHQ-12 scores increased by 93% (P = .042) and their PSWQ scores by 11% (P = .019). CONCLUSIONS These findings suggest that (1) baseline psychological distress is associated with worse outcomes in patients with early-stage MF and that (2) effective treatment improves psychological morbidity.
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Affiliation(s)
- Meagan-Helen Henderson Berg
- Division of Dermatology, McGill University, Montréal, QC, Canada
- Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada
- McGill Multidisciplinary Cutaneous Lymphoma Clinic, Montréal, QC, Canada
| | - Gizelle Popradi
- McGill Multidisciplinary Cutaneous Lymphoma Clinic, Montréal, QC, Canada
- Division of Hematology, McGill University, Montréal, QC, Canada
| | - David Roberge
- McGill Multidisciplinary Cutaneous Lymphoma Clinic, Montréal, QC, Canada
- Division of Radiation Oncology, Centre Hospitalier de l’Universite de Montreal, Montréal, QC, Canada
| | - Tina Petrogiannis-Haliotis
- McGill Multidisciplinary Cutaneous Lymphoma Clinic, Montréal, QC, Canada
- Department of Pathology, Jewish General Hospital, McGill University, Montréal, QC, Canada
- Division of Hematology, Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC, Canada
| | - Kevin Pehr
- Division of Dermatology, McGill University, Montréal, QC, Canada
- Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada
- McGill Multidisciplinary Cutaneous Lymphoma Clinic, Montréal, QC, Canada
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21
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Abdulrahman N, Leo R, Boumenar HA, Ahmad F, Mateo JM, Jochebeth A, Al-Sowaidi NK, Sher G, Ansari AW, Alam M, Uddin S, Ahmad A, Steinhoff M, Buddenkotte J. Embelin inhibits viability of cutaneous T cell lymphoma cell lines HuT78 and H9 by targeting inhibitors of apoptosis. Leuk Lymphoma 2023; 64:2236-2248. [PMID: 37708450 DOI: 10.1080/10428194.2023.2256909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 05/15/2023] [Accepted: 08/30/2023] [Indexed: 09/16/2023]
Abstract
Cutaneous T cell lymphoma (CTCL) is a varied group of neoplasms that affects the skin. Acquired resistance against chemotherapeutic drugs and associated toxic side effects are limitations that warrant search for novel drugs against CTCL. Embelin (EMB) is a naturally occurring benzoquinone derivative that has gained attention owing to its anticancer pharmacological actions and nontoxic nature. We assessed the anticancer activity of EMB against CTCL cell lines, HuT78, and H9. EMB inhibited viability of CTCL cells in a dose-dependent manner. EMB activated extrinsic and intrinsic pathways of apoptosis as shown by the activation of initiator and executioner caspases. EMB-induced apoptosis also involved suppression of inhibitors of apoptosis, XIAP, cIAP1, and cIAP2. PARP cleavage and upregulation of pH2AX indicated DNA damage induced by EMB. In conclusion, we characterized a novel apoptosis-inducing activity of EMB against CTCL cells, implicating EMB as a potential therapeutic agent against CTCL.
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Affiliation(s)
- Nabeel Abdulrahman
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Rari Leo
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Hasna Amal Boumenar
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Fareed Ahmad
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Jericha M Mateo
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Anh Jochebeth
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | | | - Gulab Sher
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Abdul W Ansari
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Majid Alam
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Shahab Uddin
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Aamir Ahmad
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Martin Steinhoff
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
- Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar
- College of Medicine, Qatar University, Doha, Qatar
- Weill Cornell Medicine, School of Medicine, Doha, Qatar
- Department of Dermatology, Weill Cornell Medicine, New York, NY, USA
| | - Joerg Buddenkotte
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
- Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar
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22
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Latzka J, Assaf C, Bagot M, Cozzio A, Dummer R, Guenova E, Gniadecki R, Hodak E, Jonak C, Klemke CD, Knobler R, Morrris S, Nicolay JP, Ortiz-Romero PL, Papadavid E, Pimpinelli N, Quaglino P, Ranki A, Scarisbrick J, Stadler R, Väkevä L, Vermeer MH, Wehkamp U, Whittaker S, Willemze R, Trautinger F. EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023. Eur J Cancer 2023; 195:113343. [PMID: 37890355 DOI: 10.1016/j.ejca.2023.113343] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/28/2023] [Accepted: 08/23/2023] [Indexed: 10/29/2023]
Abstract
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
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Affiliation(s)
- Johanna Latzka
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria; Karl Landsteiner Institute of Dermatological Research, Department of Dermatology and Venereology, University Hospital of St. Pölten, St. Pölten, Austria.
| | - Chalid Assaf
- Department of Dermatology, HELIOS Klinikum Krefeld, Krefeld, Germany; Institute for Molecular Medicine, Medical School Hamburg, University of Applied Sciences and Medical University, Hamburg, Germany; Department of Dermatology, HELIOS Klinikum Schwerin, University Campus of The Medical School Hamburg, Schwerin, Germany
| | - Martine Bagot
- Department of Dermatology, Hopital Saint Louis, Université Paris Cité, INSERM U976, Paris, France
| | - Antonio Cozzio
- Department of Dermatology and Allergology, Kantonspital St. Gallen, St. Gallen, Switzerland
| | - Reinhard Dummer
- Department of Dermatology, University of Zurich, Zurich, Switzerland
| | - Emmanuella Guenova
- Department of Dermatology, University Hospital of Lausanne and Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Robert Gniadecki
- Department of Dermatology, University of Copenhagen, Copenhagen, Denmark; Division of Dermatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Emmilia Hodak
- Cutaneous Lymphoma Unit, Davidoff Cancer Center, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Constanze Jonak
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | | | - Robert Knobler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Stephen Morrris
- Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, London, UK
| | - Jan P Nicolay
- Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany
| | - Pablo L Ortiz-Romero
- Department of Dermatology, Hospital Universitario 12 de Octubre, Institute i+12, CIBERONC, Medical School, University Complutense, Madrid, Spain
| | - Evangelia Papadavid
- National and Kapodistrian University of Athens, 2nd Department of Dermatology and Venereology, Attikon General Hospital, University of Athens, Chaidari, Greece
| | - Nicola Pimpinelli
- Department of Health Sciences, Division of Dermatology, University of Florence, Florence, Italy
| | - Pietro Quaglino
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Annamari Ranki
- Department of Dermatology and Allergology, Inflammation Center, Helsinki University Central Hospital, Helsinki, Finland
| | - Julia Scarisbrick
- Department of Dermatology, University Hospital Birmingham, Birmingham, UK
| | - Rudolf Stadler
- University Department of Dermatology, Venereology, Allergology and Phlebology, Skin Cancer Center, Johannes Wesling Medical Centre Minden, Ruhr University Bochum, Bochum, Germany
| | - Liisa Väkevä
- Department of Dermatology and Allergology, Inflammation Center, Helsinki University Central Hospital, Helsinki, Finland
| | - Maarten H Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ulrike Wehkamp
- Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Medical Department, Medical School of Hamburg, Hamburg, Germany
| | - Sean Whittaker
- St. John's Institute of Dermatology, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Franz Trautinger
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria; Karl Landsteiner Institute of Dermatological Research, Department of Dermatology and Venereology, University Hospital of St. Pölten, St. Pölten, Austria
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23
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Campbell BA, Dobos G, Haider Z, Prince HM, Bagot M, Evison F, van der Weyden C, McCormack C, Ram-Wolff C, Miladi M, Scarisbrick JJ. International study of treatment efficacy in SS shows superiority of combination therapy and heterogeneity of treatment strategies. Blood Adv 2023; 7:6639-6647. [PMID: 37648672 PMCID: PMC10628811 DOI: 10.1182/bloodadvances.2023011041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/22/2023] [Accepted: 08/22/2023] [Indexed: 09/01/2023] Open
Abstract
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.
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Affiliation(s)
- Belinda A. Campbell
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
- Department of Clinical Pathology, The University of Melbourne, Parkville, Australia
| | - Gabor Dobos
- Department of Dermatology, Hôpital Saint Louis, Université Paris Cité, Paris, France
- Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Zahra Haider
- Department of Dermatology, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - H. Miles Prince
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
- Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne Australia
| | - Martine Bagot
- Department of Dermatology, Hôpital Saint Louis, Université Paris Cité, Paris, France
| | - Felicity Evison
- Health Data Science Team, Research Development and Innovation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Carrie van der Weyden
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
- Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne Australia
| | - Chris McCormack
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
- Department of Surgery, The University of Melbourne, Parkville, Australia
| | - Caroline Ram-Wolff
- Department of Dermatology, Hôpital Saint Louis, Université Paris Cité, Paris, France
| | - Maryam Miladi
- Department of Dermatology, Hôpital Saint Louis, Université Paris Cité, Paris, France
| | - Julia J Scarisbrick
- Department of Dermatology, University Hospital Birmingham, Birmingham, United Kingdom
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24
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Guenova E, Ortiz-Romero PL, Poligone B, Querfeld C. Mechanism of action of chlormethine gel in mycosis fungoides. J Eur Acad Dermatol Venereol 2023; 37:1739-1748. [PMID: 37262305 DOI: 10.1111/jdv.19237] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/11/2023] [Indexed: 06/03/2023]
Abstract
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from early-stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health-related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem-cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment-related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin-directed therapies (SDTs) as first-line treatment for early-stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid-alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro-environment, in the specific context of MF treatment.
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Affiliation(s)
- E Guenova
- University Hospital Lausanne (CHUV), Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - P L Ortiz-Romero
- Department of Dermatology, Institute i+12, CIBERONC, Medical School, Hospital 12 de Octubre, University Complutense, Madrid, Spain
| | - B Poligone
- Rochester Skin Lymphoma Medical Group, Fairport, New York, USA
| | - C Querfeld
- Division of Dermatology, Department of Pathology, City of Hope National Medical Center, Beckman Research Institute, Duarte, California, USA
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25
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Chalaka CW, Mahurin HM, Tarabadkar E, Hippe DS, Loggers ET, Shinohara MM. Gender disparities in health-related quality of life (HRQoL) in patients with cutaneous T-cell lymphoma. Int J Womens Dermatol 2023; 9:e085. [PMID: 37284299 PMCID: PMC10241495 DOI: 10.1097/jw9.0000000000000085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 04/08/2023] [Indexed: 06/08/2023] Open
Abstract
Patients with cutaneous T-cell lymphoma (CTCL) often experience debilitating symptoms that impair health-related quality of life (HRQoL). Existing evidence for HRQoL differences with respect to gender is conflicting. Objective To investigate potential gender differences in HRQoL for patients with CTCL. Methods We performed a cross-sectional study to assess HRQoL in patients with CTCL by partnering with the Cutaneous Lymphoma Foundation to distribute an electronic survey from February to April 2019. Results A total of 292 patient responses (66% women, mean age 57 years) were included in the analysis. Most of the cohort had early-stage (IA-IIA) (74%; 162/203) mycosis fungoides (MFs) (87%; 241/279), followed by Sézary syndrome (SS) (12%; 33/279). Women with CTCL experienced significantly worse HRQoL compared with men (Skindex-16: 51±26 vs. 36±26, P ≤ 0.001; FACT-G: 69±21 vs. 77±16, P = 0.005). This gender difference was present even when controlling for stage of disease. Women experienced worse HRQoL in all three of the Skindex-16 subscales (symptoms: β = 14.0, P ≤ 0.001; emotions: β = 15.1, P ≤ 0.001; functioning: β = 11.3, P = 0.006), but only two of the four FACT-G subscales (physical: β =-2.8, P ≤ 0.001; emotional: β = -2.0, P = 0.004). Limitations Due to the method of distribution of the survey, we were unable to estimate a participant response rate. Participants' diagnosis and stage were self-reported. Conclusion In this cohort women with CTCL experienced significantly worse HRQoL when compared to men. Additional studies are necessary to determine what factors contribute to this gender disparity.
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Affiliation(s)
| | | | | | - Daniel S. Hippe
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Elizabeth T. Loggers
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Division of Hematology/Oncology, Department of Medicine, University of Washington, Seattle, WA
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26
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Beltraminelli H. Cutaneous T-cell lymphoma-Focus on some problems, and some solutions. Hematol Oncol 2023; 41 Suppl 1:20-24. [PMID: 37294972 DOI: 10.1002/hon.3147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 03/28/2023] [Indexed: 06/11/2023]
Abstract
Cutaneous lymphomas are a heterogeneous group of several distinct entities of lymphoproliferative diseases. The diagnosis of a cutaneous lymphoma is a challenge, and it is always the result of a careful analysis of several information's consisting of clinical history, clinical picture, histological and molecular analyses. For this reason, experts taking care of patients with a skin lymphoma need to know all the peculiar diagnostic elements very well, in order not to run into mistakes. In this article, we will focus the discussion on some issues as the skin biopsy (when and where). In addition, we will discuss the approach to the erythrodermic patient, whose differential diagnoses include mycosis fungoides, and Sézary syndrome, beside more frequent inflammatory conditions. Finally, we will address the issue of quality of life and the possible support of the suffering patient with a cutaneous lymphoma, well knowing that the current therapeutic possibilities are unfortunately limited.
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Affiliation(s)
- Helmut Beltraminelli
- Head of Dermatology, Responsible of Dermatopathology at Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
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27
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Latzka J, Trautinger F. Mycosis fungoides and Sézary syndrome – Review and outlook. J Dtsch Dermatol Ges 2023; 21:386-391. [PMID: 36971307 DOI: 10.1111/ddg.15051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 02/10/2023] [Indexed: 03/29/2023]
Abstract
Mycosis fungoides and Sézary syndrome are the most important representatives of the heterogeneous group of cutaneous T-cell lymphomas. The diseases are rare and the diagnosis, which always requires a clinical-pathological correlation, is often delayed, especially in early forms of mycosis fungoides. The prognosis of mycosis fungoides depends on its stage and is usually favorable in the early stages. Clinically relevant prognostic parameters are missing and their development is the subject of current clinical research. Sézary syndrome, characterized by initial erythroderma and blood involvement, is a disease with a high mortality rate, in which good responses can now be achieved in many cases with new treatment options. The pathogenesis and immunology of the diseases is heterogeneous, with recent results pointing primarily to changes in specific signal transduction pathways that may be suitable as future treatment targets. Current therapy for mycosis fungoides and Sézary syndrome is primarily palliative with topical and systemic options either used alone or in combination. Only with allogeneic stem cell transplantation durable remissions can be achieved in selected patients. Similar to other areas of oncology, the development of new therapies for cutaneous lymphomas is currently changing from relatively untargeted empiricism to disease-specific, targeted pharmacotherapy based on knowledge from experimental research.
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Affiliation(s)
- Johanna Latzka
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
- Karl Landsteiner Institute of Dermatological Research, St. Pölten, Austria
| | - Franz Trautinger
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
- Karl Landsteiner Institute of Dermatological Research, St. Pölten, Austria
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Nguyen M, LeWitt T, Pang Y, Bagnowski K, Espinosa ML, Choi J, Guitart J, Liszewski W, Zhou XA. Lifestyle, demographic and Skindex measures associated with cutaneous T-cell lymphoma: a single institution cohort study. Arch Dermatol Res 2023; 315:275-278. [PMID: 35668201 PMCID: PMC10139840 DOI: 10.1007/s00403-022-02360-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 05/07/2022] [Accepted: 05/16/2022] [Indexed: 11/24/2022]
Abstract
Cutaneous T-cell lymphoma (CTCL) risk factors and associated quality of life are poorly understood. Previous studies of CTCL risk factors explored patient comorbidities and lifestyle exposures, but not in conjunction with disease stage, subtype, severity, or health-related quality of life (HRQoL). We investigated lifestyle exposures and demographic factors associated with advanced-stage disease, increased disease severity, and poorer HRQoL outcomes in this single-center cohort study. A cohort survey study was conducted at Northwestern's Multidisciplinary Cutaneous Lymphoma specialty clinic between April 2019 and June 2021. REDCap surveys were administered to 140 patients with CTCL, investigating patients' demographics, lifestyle and chemical exposures. QoL was evaluated using the Skindex survey; pain and itch with ten-point Likert scales. Modified Severity Weighted Assessment Tool (mSWAT), disease stage, and disease subtype were confirmed upon enrollment in the study by a single board-certified dermatologist specializing in CTCL. Factors were compared by t test or Fischer's exact test. Median age was 63 years (range 14-92) with male-to-female ratio of 1.2:1. The most common diagnosis was CD4 + MF (n = 94, 67.1%). Common lifestyle exposures included smoking (past or current) (52.3%) and chemical exposure history (all sources [53.7%]; industrial only [33.0%]). History of chemical exposures were associated with advanced stage disease (p = 0.003) and worse QoL outcomes (p = 0.001). There were significant racial differences, respectively, in early (I-IIA) vs late (IIB-IV) stage disease (p = 0.003). Obesity, hygiene, smoking, recent sun exposure, education and atopy were not significantly associated with disease stage or severity. We provide an analysis of lifestyle and demographic factors in the context of CTCL disease severity, stage, and HRQoL. We identified race as a potential risk factor for advanced stage disease and both skin phototype and chemical exposures as a risk factor for increased disease severity as measured by mSWAT. QoL outcomes were multifactorial and significantly associated with history of chemical exposure, severe pain/itch, race, disease stage and subtype. An improved understanding of these associations may lead to better individualized care. As chemical exposure and race were found to be significant factors associated with advanced-stage disease, taking exposure histories and addressing racial disparities may improve care for CTCL patients.
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Affiliation(s)
- Morgan Nguyen
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Tessa LeWitt
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Yanzhen Pang
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Katherine Bagnowski
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Maria L Espinosa
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jaehyuk Choi
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Walter Liszewski
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Xiaolong Alan Zhou
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Miyashiro D, Sanches JA. Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management. Front Oncol 2023; 13:1141108. [PMID: 37124514 PMCID: PMC10140754 DOI: 10.3389/fonc.2023.1141108] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic Alibert-Bazin MF, folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin, each with characteristic clinical presentation, histopathological findings, and distinct clinical behaviors. SS is an aggressive leukemic variant of cutaneous lymphoma, and it is characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by malignant cells. There is a wide range of dermatological manifestations of MF/SS, and prompt recognition is essential for early diagnosis. Skin biopsy for histopathology and immunohistochemical analysis is imperative to confirm the diagnosis of MF/SS. Histopathology may also provide information that may influence prognosis and treatment. Staging follows the TNMB system. Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase. Treatment is divided into skin-directed therapies (topical treatments, phototherapy, radiotherapy), and systemic therapies (biological response modifiers, targeted therapies, chemotherapy). Allogeneic bone marrow transplantation and extracorporeal photopheresis are other treatment modalities used in selected cases. This review discusses the main clinical characteristics, the histopathological/immunohistochemical findings, the staging system, and the therapeutic management of MF/SS.
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Muacevic A, Adler JR, Desai SR, Chen PL, Seminario-Vidal L. Perspectives on and Quality of Life in Skin of Color Patients With Mycosis Fungoides/Sézary Syndrome: A Qualitative Analysis. Cureus 2023; 15:e34054. [PMID: 36824562 PMCID: PMC9941020 DOI: 10.7759/cureus.34054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 01/22/2023] [Indexed: 01/23/2023] Open
Abstract
Background Prior quantitative studies have described the diminished health-related quality of life (HRQoL) faced by the overall mycosis fungoides (MF)/Sézary syndrome (SS) population; yet, little is known about how the disease affects HRQoL in skin of color (SOC) patients. This qualitative study sought to explore the lived experiences of SOC patients with MF/SS and gain deeper insights into the impact the disease has on various facets of HRQoL. Methodology Interviews with SOC patients with MF/SS ≥18 were recruited from a cutaneous lymphoma clinic. A thematic analysis was performed to identify overarching themes. Results Ten patients were invited to participate from July to September 2021. One patient with SS and seven patients with MF (four in the early stage and four in the advanced stage), with a median age of 60.5 years, agreed to participate. Emerging themes included diagnostic and therapeutic delays frequently due to initial misdiagnoses with other skin conditions. Physical and functional burdens significantly hindered participants' abilities to carry out daily responsibilities and maintain employment, and impacts on physical appearance (e.g., darkened skin) led to increased self-consciousness and lack of social acceptance. Participants regarded family and faith as main sources of support in addition to developing healthy coping strategies, such as self-acceptance and adaptability. All participants reported feeling satisfied with their access to healthcare information and the quality of care received. Conclusions Our findings provide greater insights into how HRQoL is impacted across SOC patients with MF/SS, which can help raise awareness among healthcare providers and assist with creating interdisciplinary healthcare approaches to better support the needs of this population.
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Hodak E, Geskin L, Guenova E, Ortiz-Romero PL, Willemze R, Zheng J, Cowan R, Foss F, Mangas C, Querfeld C. Real-Life Barriers to Diagnosis of Early Mycosis Fungoides: An International Expert Panel Discussion. Am J Clin Dermatol 2023; 24:5-14. [PMID: 36399227 PMCID: PMC9673193 DOI: 10.1007/s40257-022-00732-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2022] [Indexed: 11/19/2022]
Abstract
Mycosis fungoides (MF) is a rare, primary cutaneous T-cell lymphoma that is challenging to diagnose due to its heterogeneous clinical presentation and complex histology. The subtlety of the initial clinical appearance of MF can result in diagnostic delays and hesitancy to refer suspected cases to specialist clinics. An unmet need remains for greater awareness and education. Therefore, an international expert panel of dermatologists, oncologists, hematologists, and dermatopathologists convened to discuss and identify barriers to early and accurate MF diagnosis that could guide clinicians toward making a correct diagnosis. Confirmation of MF requires accurate assessment of symptoms and clinical signs, and subsequent correlation with dermatopathological findings. This review summarizes the expert panel's guidance, based on the literature and real-life experience, for dermatologists to help include MF in their list of differential diagnoses, along with simple clinical and histopathologic checklists that may help clinicians to suspect and identify potential MF lesions and reduce diagnostic delays.
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Affiliation(s)
- Emmilia Hodak
- Division of Dermatology, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, 39 Jabotinsky Street, Petah Tiqva, 49100, Tel Aviv, Israel.
| | - Larisa Geskin
- Columbia University Medical Center, Columbia University, New York, NY, USA
| | - Emmanuella Guenova
- University Hospital Lausanne (CHUV) and Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Pablo L Ortiz-Romero
- Department of Dermatology, Hospital 12 de Octubre, Institute i+12, CIBERONC, Medical School, University Complutense, Madrid, Spain
| | - Rein Willemze
- Leiden University Medical Center, Leiden, The Netherlands
| | - Jie Zheng
- Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Richard Cowan
- Christie Hospital, The Christie School of Oncology, Manchester, UK
| | - Francine Foss
- Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA
| | - Cristina Mangas
- Dermatology Department and Institute of Oncology of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Christiane Querfeld
- Division of Dermatology and Department of Pathology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA
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Macagno N, Mastorino L, Rubatto M, Avallone G, Merli M, Agostini A, Fava P, Ribero S, Quaglino P. Primary cutaneous lymphoma patients seen at a referral dermatological centre in 1 year: A single-centre observational retrospective cohort study of the diagnoses and staging, comorbidities and associated symptoms, treatment performed and clinical course. J Eur Acad Dermatol Venereol 2022; 36:2388-2392. [PMID: 35881645 PMCID: PMC9804410 DOI: 10.1111/jdv.18469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/24/2022] [Indexed: 01/05/2023]
Abstract
IMPORTANCE Primary cutaneous lymphomas (PCL) are rare diseases, but the indolent course makes their prevalence high. Although there are many treatment options, no hierarchy is recommended. OBJECTIVE To identify the burden of PCL and describe clinical-pathologic features; associated comorbidities; analyse treatment approaches in real-life and the parameters associated with the achievement of complete response (CR). DESIGN, SETTING AND PARTICIPANTS In this study, all the PCL patients (384 patients) consecutively seen at the Dermatologic Clinic of the University of Turin from January 1, 2019 to December 31, 2019, with follow-up updated to December 2020, were included. MAIN OUTCOMES AND MEASURES Subtype of PCL, demographic data, time elapsed between first lesions and diagnosis, associated symptoms, comorbidities, staging at diagnosis, high-grade transformation, blood involvement, stage progression, therapies used and response were assessed. RESULTS 247 were cutaneous T-cell lymphomas (CTCL, 64.3%), 137 cutaneous B-cell lymphomas (CBCL, 35.7%) and the most frequent subtype was MF (48.4%). 62.3% of CTCL patients showed at least one comorbidity, mainly cardiovascular (28.7%), 20.2% show other not cutaneous neoplasms. The main approaches were skin-directed therapies (topical steroids 65.6%; phototherapy 50.2%). 39.3% patients achieved a CR during the disease course. Pruritus, the presence of comorbidities and high-grade transformation were factors associated with failure to achieve CR, whereas stage IA of MF was associated with greater achievement of CR. CONCLUSIONS AND RELEVANCE The Th2 cytokine related development of pruritus could justify increased resistance to treatment, while the presence of associated comorbidities could reduce treatment options as well as treatment compliance.
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Affiliation(s)
- N. Macagno
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - L. Mastorino
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - M. Rubatto
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - G. Avallone
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - M. Merli
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - A. Agostini
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - P. Fava
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - S. Ribero
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
| | - P. Quaglino
- Department of Medical Sciences, Dermatologic ClinicUniversity of TurinTurinItaly
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Ottevanger R, van Beugen S, Evers AW, Willemze R, Vermeer MH, Quint KD. Itch in patients with cutaneous T-cell lymphoma as a quality of life indicator. JAAD Int 2022; 9:57-64. [PMID: 36147217 PMCID: PMC9486110 DOI: 10.1016/j.jdin.2022.07.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2022] [Indexed: 12/01/2022] Open
Abstract
Background Cutaneous T-cell lymphoma (CTCL) is a chronic and progressive disease that has a major impact on quality of life (QoL). Objectives To describe the impact of the different stages of disease in patients with classical mycosis fungoides, folliculotropic mycosis fungoides, and Sézary syndrome on generic- and dermatology-specific QoL and the relation with itch. Methods A cross-sectional cohort study of patients with classical mycosis fungoides, folliculotropic mycosis fungoides, and Sézary syndrome was performed. Outcomes were the Skindex-29 score, Impact of Chronic Skin Disease on Daily Life which includes a visual analogue scale itch, and RAND-12. Results One hundred six patients with CTCL were included. Compared to the total mycosis fungoides group, patients with Sézary syndrome had significantly worse Skindex-29 scores. Patients with advanced disease had statistically higher scores for the symptom (P = .007), functioning (P = .002), and total score (P = .012). The degree of itching was strongly correlated with the total Skindex-29 score (R = 0.713, P < .001). Conclusion The different stages of CTCL can have a significant effect on multiple domains of generic- and dermatology-specific QoL. Itch was strongly correlated with QoL and therefore can be used as an overall QoL indicator. The effect on QoL, even in patients with early-stage disease, should not be underestimated.
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Affiliation(s)
- Rosanne Ottevanger
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
- Correspondence to: Rosanne Ottevanger, MD, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
| | - Sylvia van Beugen
- Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden, the Netherlands
| | - Andrea W.M. Evers
- Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden, the Netherlands
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Maarten H. Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Koen D. Quint
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
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Crimp C, Gangal A, Tarabadkar ES, Shinohara MM. Mechlorethamine Hydrochloride Gel in the Treatment of Mycosis Fungoides–Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Focus on Patient Selection and Special Considerations. Cancer Manag Res 2022; 14:3271-3279. [DOI: 10.2147/cmar.s351420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 11/08/2022] [Indexed: 11/23/2022] Open
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Jäger M, Özistanbullu D, Klemke CD, Tratzmiller S. [Quality of life of patients with mycosis fungoides and Sézary syndrome]. DERMATOLOGIE (HEIDELBERG, GERMANY) 2022; 73:759-764. [PMID: 36074143 DOI: 10.1007/s00105-022-05049-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/20/2022] [Indexed: 12/13/2022]
Abstract
Mycosis fungoides as the most common type and Sézary syndrome as a leukemic variant belong to the rare group of cutaneous T‑cell lymphomas. Both diseases are considered incurable and show a chronic course. Since there is no curative treatment, maintaining quality of life and relief of symptoms should be important elements when treating patients with mycosis fungoides and Sézary syndrome. Pruritus, which is a common and burdensome symptom of cutaneous T‑cell lymphoma, may negatively impact quality of life. Pruritus and quality of life can be assessed with established measurement tools. Consistent recording enables physicians to recognize restrictions in physical and psychosocial aspects of quality of life early so that therapy can be adapted.
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Affiliation(s)
- Manuel Jäger
- Hautklinik und Hauttumorzentrum, Städtisches Klinikum Karlsruhe, Akademisches Lehrkrankenhaus der Universität Freiburg, Karlsruhe, Deutschland. .,Hautklinik Städtisches Klinikum Karlsruhe, Moltkestr. 120, 76187, Karlsruhe, Deutschland.
| | - Deniz Özistanbullu
- Klinik für Dermatologie, Venerologie und Allergologie, Uniklinikum Frankfurt am Main, Frankfurt am Main, Deutschland
| | - Claus-Detlev Klemke
- Hautklinik und Hauttumorzentrum, Städtisches Klinikum Karlsruhe, Akademisches Lehrkrankenhaus der Universität Freiburg, Karlsruhe, Deutschland
| | - Sabine Tratzmiller
- Hautklinik und Hauttumorzentrum, Städtisches Klinikum Karlsruhe, Akademisches Lehrkrankenhaus der Universität Freiburg, Karlsruhe, Deutschland
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Terhorst-Molawi D, Lohse K, Ginter K, Puhl V, Metz M, Hu M, Maurer M, Altrichter S. Mast cells and tryptase are linked to itch and disease severity in mycosis fungoides: Results of a pilot study. Front Immunol 2022; 13:930979. [PMID: 36032167 PMCID: PMC9400509 DOI: 10.3389/fimmu.2022.930979] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/20/2022] [Indexed: 11/13/2022] Open
Abstract
IntroductionIn mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, itch is a frequent clinical symptom. Whether mast cells (MCs), eosinophils (Eos) or their mediators play a role in MF-associated itch or disease severity is controversially discussed. Here, we explored the role of MC and Eo numbers in the skin as well as blood levels of their mediators in disease severity and itch.MethodsIn 10 patients with MF and 10 matched control subjects we assessed disease severity, itch, and quality of life impairment using dedicated tools such as the mSWAT, ItchyQoL and DLQI. We analyzed skin biopsies and measured serum levels of tryptase, a mast cell mediator, as well as of the eosinophil products eosinophil cationic protein (ECP) and major basic protein (MBP).ResultsThe presence of chronic itch, in four of 10 patients, was associated with significantly higher disease severity (mSwat), larger body surface area affected, and stronger QoL impairment (Itchy-Qol, DLQI). Serum levels of tryptase, but not ECP and MBP, were linked with patient-reported disease severity, body surface area affected, and the presence of itch. Three of the four patients with chronic itch, but none of the six patients without, had tryptase levels above >6µg/l. Numbers of MCs in the papillary dermis were higher in MF skin lesions then in non-lesional skin of MF patients and skin of healthy controls.DiscussionThe MC-mediator tryptase, in MF, is linked to disease activity and impact, most prominently to itch. Our findings call for larger studies that explore the role of MCs, tryptase and other MC mediators as drivers of itch and their role in MF pathogenesis.
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Affiliation(s)
- Dorothea Terhorst-Molawi
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
- Institute of Clinical Physiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Katharina Lohse
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
| | - Katharina Ginter
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
| | - Viktoria Puhl
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
| | - Martin Metz
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
| | - Man Hu
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
| | - Marcus Maurer
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
- *Correspondence: Marcus Maurer,
| | - Sabine Altrichter
- Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
- Department of Dermatology and Venerology, Kepler University Hospital, Linz, Austria
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Olsen EA, Whittaker S, Willemze R, Pinter-Brown L, Foss F, Geskin L, Schwartz L, Horwitz S, Guitart J, Zic J, Kim YH, Wood GS, Duvic M, Ai W, Girardi M, Gru A, Guenova E, Hodak E, Hoppe R, Kempf W, Kim E, Lechowicz MJ, Ortiz-Romero P, Papadavid E, Quaglino P, Pittelkow M, Prince HM, Sanches JA, Sugaya M, Vermeer M, Zain J, Knobler R, Stadler R, Bagot M, Scarisbrick J. Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC. Blood 2022; 140:419-437. [PMID: 34758074 PMCID: PMC9353153 DOI: 10.1182/blood.2021012057] [Citation(s) in RCA: 97] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 10/15/2021] [Indexed: 11/20/2022] Open
Abstract
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
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Affiliation(s)
- Elise A Olsen
- Department of Dermatology and Department of Medicine, Division of Hematologic Malignancies, Duke University Medical Center, Durham, NC
| | - Sean Whittaker
- School of Basic and Medical Biosciences, Kings College London and St. Johns Institute of Dermatology, London, United Kingdom
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Lauren Pinter-Brown
- Departments of Medicine and Dermatology, Chao Family Comprehensive Cancer Center, University of California-Irvine, Irvine, CA
| | - Francine Foss
- Hematology and Stem Cell Transplantation, Yale University School of Medicine, New Haven, CT
| | - Larisa Geskin
- Department of Dermatology, Columbia University Medical Center, New York, NY
| | - Lawrence Schwartz
- Department of Radiology, Columbia University Medical Center, New York, NY
| | - Steven Horwitz
- Department of Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Joan Guitart
- Departments of Dermatology and Pathology, Northwestern University, Chicago, IL
| | - John Zic
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN
| | - Youn H Kim
- Department of Dermatology, Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA
| | - Gary S Wood
- Department of Dermatology, University of Wisconsin-Madison, Madison, WI
| | - Madeleine Duvic
- University of Texas MD Anderson Cancer Center, Dermatology Unit, Houston, TX
| | - Wei Ai
- Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, CA
| | - Michael Girardi
- Department of Dermatology, Yale School of Medicine, New Haven, CT
| | - Alejandro Gru
- Divisions of Dermatopathology and Hematopathology, Department of Pathology, Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA
| | - Emmanuella Guenova
- Department of Dermatology, Lausanne University Hospital, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Emmilia Hodak
- Division of Dermatology, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, Tel Aviv, Israel
| | - Richard Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, CA
| | - Werner Kempf
- Department of Dermatology, University Hospital Zurich and Kempf and Pfaltz Histologische Diagnostik, Zurich, Switzerland
| | - Ellen Kim
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Mary Jo Lechowicz
- Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA
| | - Pablo Ortiz-Romero
- Department of Dermatology, Hospital Universitario 12 de Octubre, i+12 Institute, CIBERONC, Medical School, Universidad Complutense, Madrid, Spain
| | - Evangelia Papadavid
- Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Athens, Greece
| | - Pietro Quaglino
- Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Turin, Italy
| | - Mark Pittelkow
- Department of Dermatology, Mayo Clinic Arizona, Scottsdale, AZ
| | - H Miles Prince
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Jose Antonio Sanches
- Department of Dermatology, University of Sao Paulo Medical School, São Paulo, Brazil
| | - Makoto Sugaya
- Department of Dermatology, International University of Health and Welfare, Chiba, Japan
| | - Maarten Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jasmine Zain
- Department of Hematology and Hematopoetic Stem Cell Transplantation, City of Hope National Medical Center, Duarte, CA
| | - Robert Knobler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Rudolf Stadler
- University Clinic for Dermatology, Johannes Wesling Medical Centre, University of Bochum, Minden, Germany
| | - Martine Bagot
- Department of Dermatology, Université de Paris, AP-HP, Hôpital Saint-Louis, Paris, France; and
| | - Julia Scarisbrick
- Department of Dermatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
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Mukumoto N, Inokuchi H, Hamaura N, Yamagishi M, Sakagami M, Matsuda S, Hayashi D, Tsuruta D, Shibuya K. Low-Dose Volumetric Modulated Arc Therapy for a Patient With Head and Neck Involvement of Mycosis Fungoides: A Case Report With a Review of Literature. Cureus 2022; 14:e26217. [PMID: 35891857 PMCID: PMC9307425 DOI: 10.7759/cureus.26217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2022] [Indexed: 11/15/2022] Open
Abstract
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma that slowly progresses over a period of years to decades. In some cases, lesions that spread to the scalp, neck, or facial skin can have a significant impact on cosmetic appearance and a patient's quality of life. Among the various treatments, radiation therapy is one of the most effective treatment modalities for patients with symptomatic cutaneous lesions. We report on an MF patient who had gradually increasing patches and plaques on the scalp, face, and neck and who underwent irradiation with 20 Gy administered in 10 fractions using volumetric modulated arc therapy. After undergoing this highly conformal technique, the patient obtained prolonged local control and significant alleviation of symptoms with acceptable adverse events. This technique constitutes a promising approach for treating a complex target due to its ability to provide homogeneous coverage of irregularly shaped target volumes along with its ability to preserve organs at risk. In addition, we systematically reviewed clinical reports on the management of extensive cutaneous lesions in MF patients undergoing other irradiation techniques.
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Dippel E, Assaf C, Becker JC, von Bergwelt-Baildon M, Bernreiter S, Cozzio A, Eich HT, Elsayad K, Follmann M, Grabbe S, Hillen U, Klapper W, Klemke CD, Loquai C, Meiss F, Mitteldorf C, Wehkamp U, Nashan D, Nicolay JP, Oschlies I, Schlaak M, Stranzenbach R, Moritz R, Stoll C, Vag T, Weichenthal M, Wobser M, Stadler R. S2k-Leitlinie - Kutane Lymphome (ICD10 C82-C86): Update 2021. J Dtsch Dermatol Ges 2022; 20:537-555. [PMID: 35446484 DOI: 10.1111/ddg.14706_g] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
| | - Chalid Assaf
- Klinik für Dermatologie und Venerologie, Helios Klinikum Krefeld
| | | | | | | | - Antonio Cozzio
- Klinik für Dermatologie, Venerologie und Allergologie, Kantonsspital St. Gallen
| | - Hans T Eich
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Münster
| | - Khaled Elsayad
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Münster
| | | | | | - Uwe Hillen
- Klinik für Dermatologie, Universitätsklinikum Essen
| | - Wolfram Klapper
- Institut für Pathologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Claus-Detlev Klemke
- Hautklinik, Städtisches Klinikum Karlsruhe, Akademisches Lehrkrankenhaus der Universität Freiburg, Karlsruhe
| | | | - Frank Meiss
- Klinik für Dermatologie und Venerologie, Universitätsklinik Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Christina Mitteldorf
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen
| | - Ulrike Wehkamp
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | | | - Jan P Nicolay
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinik Mannheim
| | - Ilske Oschlies
- Institut für Pathologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Max Schlaak
- Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin
| | - René Stranzenbach
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum der Ruhr-Universität Bochum
| | - Rose Moritz
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Halle
| | | | - Tibor Vag
- Nuklearmedizinische Klinik, Klinikum Rechts der Isar, Technische Universität München
| | - Michael Weichenthal
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Marion Wobser
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg
| | - Rudolf Stadler
- Klinik für Dermatologie, Venerologie, Allergologie und Phlebologie, Johannes Wesling Universitätsklinikum Minden, Universitätsklinikum der Ruhr-Universität Bochum
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Dippel E, Assaf C, Becker JC, von Bergwelt‐Baildon M, Bernreiter S, Cozzio A, Eich H
T, Elsayad K, Follmann M, Grabbe S, Hillen U, Klapper W, Klemke C, Loquai C, Meiss F, Mitteldorf C, Wehkamp U, Nashan D, Nicolay JP, Oschlies I, Schlaak M, Stranzenbach R, Moritz R, Stoll C, Vag T, Weichenthal M, Wobser M, Stadler R. S2k-Guidelines - Cutaneous lymphomas (ICD10 C82 - C86): Update 2021. J Dtsch Dermatol Ges 2022; 20:537-554. [PMID: 35446497 PMCID: PMC9325452 DOI: 10.1111/ddg.14706] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Edgar Dippel
- Department of DermatologyHospital LudwigshafenGermany
| | - Chalid Assaf
- Department of Dermatology and VenereologyHelios Hospital KrefeldGermany
| | | | | | | | - Antonio Cozzio
- Department of DermatologyVenereology and AllergologyCanton Hospital St. GallenSwitzerland
| | - Hans
T. Eich
- Department of Radiation Therapy and Radio‐OncologyUniversity Hospital MünsterGermany
| | - Khaled Elsayad
- Department of Radiation Therapy and Radio‐OncologyUniversity Hospital MünsterGermany
| | | | - Stephan Grabbe
- Department of DermatologyUniversity Hospital MainzGermany
| | - Uwe Hillen
- Department of DermatologyUniversity Hospital EssenGermany
| | - Wolfram Klapper
- Institute of PathologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Claus‐Detlev Klemke
- Department of DermatologyMunicipal Hospital of KarlsruheAcademic Teaching Hospital for the University of FreiburgKarlsruheGermany
| | - Carmen Loquai
- Department of DermatologyUniversity Hospital MainzGermany
| | - Frank Meiss
- Department of Dermatology and VenereologyUniversity Hospital Freiburgmedical FacultyAlbert‐Ludwigs University FreiburgGermany
| | - Christina Mitteldorf
- Department of DermatologyVenereology and AllergologyUniversity Hospital GöttingenGermany
| | - Ulrike Wehkamp
- Department of DermatologyVenereology and AllergologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Dorothee Nashan
- Department of DermatologyDortmund Hospital GmbHDortmundGermany
| | - Jan P. Nicolay
- Department of DermatologyVenereology and AllergologyUniversity Hospital MannheimGermany
| | - Ilske Oschlies
- Institute of PathologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Max Schlaak
- Charité
– Universitätsmedizin BerlinDepartment of DermatologyVenereology and AllergologyBerlinGermany
| | - René Stranzenbach
- Department of DermatologyVenereology and AllergologyUniversity Hospital at Ruhr University BochumGermany
| | - Rose Moritz
- Department for DermatologyUniversity Hospital HalleGermany
| | | | - Tibor Vag
- Department of Nuclear MedicineTechnical University of MunichGermany
| | - Michael Weichenthal
- Department of DermatologyVenereology and AllergologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Marion Wobser
- Department of DermatologyVenereology and AllergologyUniversity Hospital WürzburgGermany
| | - Rudolf Stadler
- Department of DermatologyVenereologyAllergologyand PhlebologyJohannes Wesling University Hospital MindenUniversity Hospital at Ruhr University BochumGermany
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Licht P, Mailänder V. Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma. Cells 2022; 11:cells11030328. [PMID: 35159138 PMCID: PMC8834405 DOI: 10.3390/cells11030328] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 12/31/2021] [Accepted: 01/13/2022] [Indexed: 11/16/2022] Open
Abstract
Cutaneous T-Cell Lymphomas (CTCL) presents with substantial clinical variability and transcriptional heterogeneity. In the recent years, several studies paved the way to elucidate aetiology and pathogenesis of CTCL using sequencing methods. Several T-cell subtypes were suggested as the source of disease thereby explaining clinical and transcriptional heterogeneity of CTCL entities. Several differentially expressed pathways could explain disease progression. However, exogenous triggers in the skin microenvironment also seem to affect CTCL status. Especially Staphylococcus aureus was shown to contribute to disease progression. Only little is known about the complex microbiome patterns involved in CTCL and how microbial shifts might impact this malignancy. Nevertheless, first hints indicate that the microbiome might at least in part explain transcriptional heterogeneity and that microbial approaches could serve in diagnosis and prognosis. Shaping the microbiome could be a treatment option to maintain stable disease. Here, we review current knowledge of transcriptional heterogeneity of and microbial influences on CTCL. We discuss potential benefits of microbial applications and microbial directed therapies to aid patients with CTCL burden.
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Affiliation(s)
- Philipp Licht
- Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany;
| | - Volker Mailänder
- Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany;
- Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
- Correspondence:
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The Role of Tumor Microenvironment in the Pathogenesis of Sézary Syndrome. Int J Mol Sci 2022; 23:ijms23020936. [PMID: 35055124 PMCID: PMC8781892 DOI: 10.3390/ijms23020936] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/11/2021] [Accepted: 12/19/2021] [Indexed: 02/05/2023] Open
Abstract
Sézary syndrome is an aggressive leukemic variant of cutaneous T-cell lymphomas, characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by CD4+ malignant T-cells. The pathogenesis of Sézary syndrome is not fully understood. However, the course of the disease is strongly influenced by the tumor microenvironment, which is altered by a combination of cytokines, chemokines, and growth factors. The crosstalk between malignant and reactive cells affects the immunologic response against tumor cells causing immune dysregulation. This review focuses on the interaction of malignant Sézary cells and the tumor microenvironment.
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Increased Chlormethine-Induced DNA Double-Stranded Breaks in Malignant T Cells from Mycosis Fungoides Skin Lesions. JID INNOVATIONS 2022; 2:100069. [PMID: 34977846 PMCID: PMC8683611 DOI: 10.1016/j.xjidi.2021.100069] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 01/16/2023] Open
Abstract
Mycosis fungoides (MF) is a type of cutaneous T-cell lymphoma. Chlormethine (CL) is recommended as first-line therapy for MF, with a major purpose to kill tumor cells through DNA alkylation. To study the extent of treatment susceptibility and tumor specificity, we investigated the gene expression of different DNA repair pathways, DNA double-stranded breaks, and tumor cell proliferation of clonal TCR Vβ+ tumor cell populations in cutaneous T-cell lymphoma skin cells on direct exposure to CL. Healthy human T cells were less susceptible to CL exposure than two T-lymphoma cell lines, resulting in higher proportions of viable cells. Interestingly, in T cells from MF lesions, we observed a downregulation of several important DNA repair pathways, even complete silencing of RAD51AP1, FANC1, and BRCA2 involved in homologous recombination repair. In the presence of CL, the double-stranded DNA breaks in malignant MF skin T cells increased significantly as well as the expression of the apoptotic gene CASP3. These data point toward an important effect of targeting CL on MF skin tumor T cells, which support CL use as an early cutaneous lymphoma treatment and can be of synergistic use, especially beneficial in the setting of combination skin-directed therapies for cutaneous T-cell lymphoma.
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Salant JA, Khan N, Nelson JE, Norton-Westbrook M, Desai AV. Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Cutaneous T Cell Lymphoma. J Palliat Med 2021; 25:958-963. [PMID: 34978848 DOI: 10.1089/jpm.2021.0610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Cutaneous T cell lymphoma and its subtypes, mycosis fungoides (MF) and Sézary syndrome (SS), comprise a spectrum of chronic lymphoproliferative disorders in which neoplastic T cells accumulate within the skin and visceral organs. This process is frequently characterized by severe pain, nonpain symptoms, and physical disfigurement. Significant emotional, spiritual, and existential distress is also felt by many of these patients as they experience a chronic, often incurable disease. Patients suffering from these diseases, though not commonly encountered, can benefit greatly from palliative care support. In this article, a team of palliative care clinicians, critical care physicians, and an oncologist specializing in lymphoma offer 10 tips to help palliative care teams to support these vulnerable and often-distressed patients and their caregivers.
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Affiliation(s)
- Jennifer A Salant
- Pediatric Advanced Care Team, Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA
| | - Niloufer Khan
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
| | - Judith E Nelson
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
- Supportive Care Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Critical Care Service, Department of Anesthesia and Critical Care, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Moe Norton-Westbrook
- Supportive Care Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Anjali V Desai
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
- Supportive Care Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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45
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Podkonjak T, Cranmer H, Scarisbrick J, McCarthy G, Lilley C, Cheng LI. Cost-effectiveness of brentuximab vedotin for the treatment of cutaneous T-cell lymphoma. J Comp Eff Res 2021; 11:193-202. [PMID: 34879742 DOI: 10.2217/cer-2021-0201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To assess the cost-effectiveness of brentuximab vedotin (BV) versus physician's choice (methotrexate or bexarotene) for treating advanced cutaneous T-cell lymphoma. Materials & methods: A partitioned-survival model was developed from the National Health Service perspective in England and Wales. Model inputs were informed by the ALCANZA trial, real-world UK data, published literature or clinical experts. Results: Over the modeled lifetime, BV dominated physician's choice and provided an additional 1.58 life-years and 1.09 higher quality-adjusted life years with a net cost saving of £119,565. The net monetary benefit was £152,326 using a willingness-to-pay threshold of £30,000/quality-adjusted life year. Results were robust in sensitivity and scenario analyses. Conclusion: BV is a highly cost-effective treatment for advanced cutaneous T-cell lymphoma.
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Affiliation(s)
| | - Holly Cranmer
- Takeda Pharmaceuticals International Co., London, UK
| | - Julia Scarisbrick
- Department of Dermatology, University Hospital Birmingham, Birmingham B15 2TH, UK
| | | | | | - Lung-I Cheng
- Global Value & Access Oncology, Takeda Pharmaceutical America, Inc., Lexington, MA 02421, USA
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46
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Musiek ACM, Rieger KE, Bagot M, Choi JN, Fisher DC, Guitart J, Haun PL, Horwitz SM, Huen AOL, Kwong BY, Lacouture ME, Noor SJ, Rook AH, Seminario-Vidal L, Vermeer MH, Kim YH. Dermatologic Events Associated with the Anti-CCR4 Antibody Mogamulizumab: Characterization and Management. Dermatol Ther (Heidelb) 2021; 12:29-40. [PMID: 34816383 PMCID: PMC8776934 DOI: 10.1007/s13555-021-00624-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Indexed: 11/30/2022] Open
Abstract
The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event. The objective of this report was to combine results from published literature with experiences and recommendations from multiple investigators and institutions into clinical best practice recommendations to assist healthcare providers in identifying and managing mogamulizumab-associated rash. Optimal management, which includes biopsy confirmation and steroid treatment, requires a multidisciplinary approach among oncology, dermatology, and pathology practitioners.
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Affiliation(s)
- Amy C M Musiek
- Division of Dermatology, Washington University School of Medicine, 4901 Forest Park, Suite 502, Saint Louis, MO, 63108, USA.
| | | | - Martine Bagot
- Hôpital Saint Louis, APHP, Inserm U976, Université de Paris, Paris, France
| | | | | | | | - Paul L Haun
- University of Pennsylvania, Philadelphia, PA, USA
| | | | | | | | | | - Sarah J Noor
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alain H Rook
- University of Pennsylvania, Philadelphia, PA, USA
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Farabi B, Seminario-Vidal L, Jamgochian M, Akay BN, Atak MF, Rao BK, Karagaiah P, Grabbe S, Goldust M. Updated review on prognostic factors in mycosis fungoides and new skin lymphoma trials. J Cosmet Dermatol 2021; 21:2742-2748. [PMID: 34687485 DOI: 10.1111/jocd.14528] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/04/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Ten-year survival rates in mycosis fungoides (MF) broadly varies, however, there is no standardized prognostic index available. This is presumably due to low prevalence, heterogeneity, and diagnostic challenges in MF. Recent studies have focused on identifying objective prognostic indices by using different parameters for survival determinants. The Cutaneous Lymphoma International Prognostic Index (CLIPI) and the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) represent prototypical studies that identify prognostic factors, seeking to improve management and outcomes in early-stage MF. Detecting these factors and stratifying MF patients according to their disease progression risk may help to manage these patients more efficiently. AIMS Review the current literature to determine the risk factors determining prognosis in MF. METHODOLOGY A Comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar" using key words 'prognostic factor', 'prognostic indicator', 'mycosis fungoides', 'Sezary syndrome', 'Skin Lymphoma', 'Cutaneous Lymphoma'. Articles published in English language were considered for the review. RESULTS The strongest prognostic factor in MF patients is the stage of the disease. T stage and the presence of extracutaneous disease are the most important factors for survival. Other factors that are associated with worse prognosis are male gender, age >60, presence of plaques, folliculotropism, eosinophilia and lymph node stage above N1/Nx. Elevated LDH was associated with later tumor stages and large cell phenotype at diagnosis had a better prognosis. KIR3DL2 was associated with malignant transformation. CONCLUSION The PROCLIPI study has assessed risk factors collected in MF patients from different countries and across different ethnicities following a rigorous clinicopathologic process. The findings presented here illustrated that disease prognosis in early stages depends on many contributing factors. Detection and stratification of such factors may allow a personalized approach to management of these patients.
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Affiliation(s)
- Banu Farabi
- Department of Internal Medicine, Saint Peter's University Hospital, New Brunswick, New Jersey, USA
| | - Lucia Seminario-Vidal
- Department of Dermatology, Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, University of South Florida Health Morsani College of Medicine, Tampa, Florida, USA
| | - Marielle Jamgochian
- Department of Dermatology, Robert Wood Johnson Medical Center, Rutgers University, New Brunswick, New Jersey, USA
| | | | | | - Babar K Rao
- Dermatology Department, Weil Cornell Medicine, NY, Somerset, New Jersey, USA
| | - Priyanka Karagaiah
- Department of dermatology, Bangalore Medical College and Research Institute, Bangalore, India
| | - Stephan Grabbe
- Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Mohamad Goldust
- Department of Dermatology, University Medical Center Mainz, Mainz, Germany
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48
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Jonak C, Tittes J, Brunner PM, Guenova E. Mycosis fungoides und Sézary-Syndrom. J Dtsch Dermatol Ges 2021; 19:1307-1335. [PMID: 34541808 DOI: 10.1111/ddg.14610_g] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 07/22/2021] [Indexed: 12/15/2022]
Affiliation(s)
- Constanze Jonak
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | - Julia Tittes
- Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Österreich
| | | | - Emmanuella Guenova
- Universitätsklinik für Dermatologie, Fakultät für Biologie und Medizin, Universität Lausanne, Lausanne, Schweiz
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49
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Jonak C, Tittes J, Brunner PM, Guenova E. Mycosis fungoides and Sézary syndrome. J Dtsch Dermatol Ges 2021; 19:1307-1334. [PMID: 34541796 PMCID: PMC9293091 DOI: 10.1111/ddg.14610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 07/22/2021] [Indexed: 11/30/2022]
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are primary cutaneous T-cell lymphomas (CTCL) with not yet fully understood etiology and pathogenesis. Conceptually, MF and SS are classified as distinct entities arising from different T helper cell subsets. MF is the most common CTCL entity, while SS is very rare. MF presents clinically with patch, plaque and/or tumor stages, but can also evolve as erythroderma, which in turn is pathognomonic for SS. SS is characterized by a detectable tumor-cell burden (Sézary cells) in the peripheral blood consistent with advanced-stage disease and a poor prognosis. In early-stage disease of MF, which is the predominant form, the prognosis is generally favorable. However, in up to 30 % of patients, there is progression of skin lesions, which can ultimately lead to visceral involvement. The histological manifestation of MF can be subtle in early-stage disease and therefore a careful clinicopathological correlation is paramount. The treatment of MF/SS is dependent on the disease stage. Therapeutic options include both skin-directed and systemic regimens. Apart from allogeneic stem cell transplantation (alloSCT), there is as yet no curative therapy for MF/SS. Accordingly, the treatment approach is symptom oriented and aims to reduce the tumor burden and improve health-related quality of life. However, the therapeutic landscape for CTCL is constantly being expanded by the discovery of novel therapeutic targets.
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Affiliation(s)
- Constanze Jonak
- Department of Dermatology, Medical University of Vienna, Austria
| | - Julia Tittes
- Department of Dermatology, Medical University of Vienna, Austria
| | | | - Emmanuella Guenova
- Department of Dermatology, Faculty of Biology and Medicine, University of Lausanne, Switzerland
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50
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Shinohara M, Mahurin H, Tarabadkar E, Hippe D, Lachance K, Kim E, Loggers E. Health‐related quality of life in cutaneous T‐cell lymphoma: A cross‐sectional survey study. SKIN HEALTH AND DISEASE 2021; 1:e45. [PMID: 35663135 PMCID: PMC9060149 DOI: 10.1002/ski2.45] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/15/2021] [Accepted: 05/03/2021] [Indexed: 01/26/2023]
Affiliation(s)
- M.M. Shinohara
- Division of Dermatology University of Washington Seattle Washington USA
| | - H.M. Mahurin
- School of Medicine University of Washington Seattle Washington USA
| | - E. Tarabadkar
- Department of Dermatology Emory University Atlanta Georgia USA
| | - D.S. Hippe
- Department of Radiology University of Washington Seattle Washington USA
| | - K. Lachance
- Division of Dermatology University of Washington Seattle Washington USA
| | - E.J. Kim
- Department of Dermatology University of Pennsylvania Philadelphia Pennsylvania USA
| | - E.T. Loggers
- Clinical Research Division Fred Hutchinson Cancer Research Center Seattle Washington USA
- Division of Hematology/Oncology Department of Medicine University of Washington Seattle Washington USA
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