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Valente M, Sanches JA, Nukui Y, Cury-Martins J, Souza BC, Pereira J, Miyashiro D. Characterization of adult T-cell leukemia/lymphoma patients with specific skin lesions in a tertiary dermatological service in Brazil. Front Med (Lausanne) 2025; 12:1505865. [PMID: 39991055 PMCID: PMC11842934 DOI: 10.3389/fmed.2025.1505865] [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: 10/03/2024] [Accepted: 01/15/2025] [Indexed: 02/25/2025] Open
Abstract
Introduction Human T-lymphotropic virus type-1 (HTLV-1) is endemic in some countries, including Brazil. HTLV-1 is the etiological agent of adult T-cell leukemia-lymphoma (ATLL), a rare and aggressive CD4+ T-lymphocyte malignancy. ATLL affects 1-5% of virus carriers. Dermatological involvement occurs in 40-70%. Diagnosis is based on clinicopathologic correlation and HTLV-1 serology. There are few therapeutic options so far. Methods This is an observational retrospective cohort study with ATLL patients followed in a tertiary hospital in São Paulo, Brazil. Data were collected at diagnosis. Survival curves using the Kaplan-Meier method were analyzed with log-rank test, univariate and multivariate analyses were performed with the Cox proportional hazards model. Results Forty-four patients were studied, 24 females (54.5%), and 20 males (45.5%). The median age at diagnosis was 59.4 years. Classification at diagnosis was: 16 (36.4%) chronic (93.7% unfavorable, 6.2% favorable), 14 (31.8%) acute, 10 (22.7%) smoldering, four (9.1%) lymphoma, and none with primary cutaneous tumoral. Regarding skin lesions, 18 (40.9%) had plaques; 15 (34.1%) nodules/tumors; 11 (25.0%) papules; 10 (22.7%) erythroderma; seven (15.9%) patches; two (4.5%) ichthyosis; one (2.3%) purpuric lesions. Epidermotropism/exocytosis of lymphocytes was observed in 25 patients (62.5%), and Pautrier microabscesses in three (7.3%). Four patients (10.0%) had subcutaneous involvement, two (5.0%) folliculotropism, two (5.0%) angiocentrism, and one (2.5%) perineural involvement. Ten patients (25.0%) presented a lichenoid pattern. Thirty-four patients (79.1%) had increased lactate dehydrogenase; 20 (45.5%) lymphocytosis; six (13.6%) flower cells in peripheral blood; six (14.6%) hypercalcemia; five (12.2%) hypoalbuminemia. Beta-2 microglobulin was increased in all 24 cases investigated. Monoclonal T-lymphocytes were observed in the blood of 23 patients (76.7%) and the skin of 19 (76.0%). Thirty patients (68.2%) died. Median overall survival was 32.3 months. Acute and chronic unfavorable forms had worse prognoses, with median overall survival of 23.3 and 34.1 months, respectively (p = 0.0011). After multivariate analysis, Shimoyama classification (acute) and urea levels were associated with poorer prognoses. Conclusion We described a large Brazilian cohort of ATLL with cutaneous involvement. Description of clinical, pathology, laboratory, and follow-up data, and factors associated with poorer survival is essential to provide better care and to improve the quality of life of these patients.
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Affiliation(s)
- Mariana Valente
- Department of Dermatology, University of São Paulo, São Paulo, Brazil
| | | | - Youko Nukui
- Discipline of Hematology, University of São Paulo, São Paulo, Brazil
| | - Jade Cury-Martins
- Department of Dermatology, University of São Paulo, São Paulo, Brazil
| | | | - Juliana Pereira
- Discipline of Hematology, University of São Paulo, São Paulo, Brazil
| | - Denis Miyashiro
- Department of Dermatology, University of São Paulo Medical School, São Paulo, Brazil
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Campbell BA, Prince HM, Thursky K, Dabaja B, Hoppe R, Specht L, Morris S, Porceddu SV. Breaking Down the Barriers for Patients With Cutaneous T-Cell Lymphoma: Current Controversies and Challenges for Radiation Oncologists in 2024. Semin Radiat Oncol 2025; 35:110-125. [PMID: 39672636 DOI: 10.1016/j.semradonc.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2024]
Abstract
Cutaneous T-cell lymphomas (CTCL) are a rare collection of diseases, frequently associated with diagnostic challenges and complex management dilemmas. The multidisciplinary team is vital for accurate clinico-pathological diagnoses and for collaborative therapeutic decisions throughout the management journey, which frequently involves multiple lines of therapy. Radiotherapy (RT) is a highly effective skin-directed therapy for CTCL, commonly delivered as localised fields or as total skin electron beam therapy (TSEBT). Mycosis fungoides (MF) is the most common of the CTCL, and patients typically experience high rates of morbidity and long natural histories of relapse and progression. Patients with MF typically present with incurable disease; in these patients, RT has an established role in symptom- and disease-control, achieving excellent response rates and proven therapeutic benefits. The role of RT continues to evolve, with modern practices favouring lower doses to reduce toxicity risks and allow for re-irradiation. Less commonly, there are situations where RT has an integral role in the potential cure of patients with MF: firstly, in the setting of unilesional MF where localised RT alone may be curative, and secondly, in the setting of preconditioning prior to curative-intent allogeneic hematopoietic stem cell transplant for patients with advanced MF/Sezary syndrome, where conventional-dose TSEBT is indicated as the most effective single agent for maximal debulking of skin disease. Radiotherapy also has an important role in the management of the less common CTCL, including the curative treatment of localised primary cutaneous anaplastic large cell lymphoma. Despite proven efficacy and quality of life benefits, disparity exists in access to RT and TSEBT. World-wide, stronger multidisciplinary collaborations and greater patient advocacy are required to increase access to RT and improve equity of care for our patients with CTCL.
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Affiliation(s)
- Belinda A Campbell
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
| | - H Miles Prince
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia; Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Karin Thursky
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia; Department of Health Services Research and Implementation Science, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Bouthaina Dabaja
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Richard Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, CA, USA
| | - Lena Specht
- Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Stephen Morris
- Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Sandro V Porceddu
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Department of Radiology, The University of Melbourne, Parkville, Victoria, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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Purnak S, Hosing C, Dabaja B, Bassett RL, Huen A, Duvic M. On the Way to Curing Advanced-Stage Mycosis Fungoides/Sézary Syndrome. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:827-836. [PMID: 39107202 DOI: 10.1016/j.clml.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/05/2024] [Accepted: 07/11/2024] [Indexed: 08/09/2024]
Abstract
INTRODUCTION/BACKGROUND Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have poor prognosis with median survivals of less than 5 years. Although a variety of treatments are approved for MF/SS patients, durable complete remissions (CR) are rare. PATIENTS AND METHODS Advanced-stage MF or SS patients who achieved CR and maintained in CR or stage IA for more than 10 years were identified by a retrospective search of the principal investigator's database. RESULTS Of 2266 patients diagnosed with MF or SS, 23 patients with advanced-stage MF/SS (6 IIB, 1 IIIB, 5 IVA1, 3 IVA2, 8 IVB) who achieved CR and maintained in CR or stage IA for ≥ 10 years were identified. As final/curative treatment, 11 patients underwent allogeneic stem cell transplantation (SCT). Most patients presented at young age, underwent SCT with reduced intensity conditioning regimen, had matched related donors, and controllable post-transplant graft versus host disease. Eleven patients were treated with TSEB as part of combined modality protocol in 2 patients and debulking therapy before allogeneic SCT in 9 patients. Five stage IIB patients achieved CR with radiotherapy. Four patients with blood involvement were treated with extracorporeal photopheresis (ECP) in combination with long-term antibiotics and immunomodulatory agents. Long-term antibiotics were given to 14 patients. CONCLUSION TSEB followed by allogeneic SCT, radiotherapy, ECP plus long-term antibiotics and immunomodulatory agents were the most common curative/final treatments found in our patients. We are reporting the details of our long-term complete responders' treatment course in the hopes of obtaining more cure responses in the future.
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Affiliation(s)
- Seda Purnak
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX.
| | - Chitra Hosing
- Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bouthaina Dabaja
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Roland L Bassett
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Auris Huen
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Madeleine Duvic
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Xu ZF, Chen H, Liu Y, Zhang W, Jin H, Liu J. A retrospective study of prognostic factors and treatment outcome in advanced-stage Mycosis Fungoides and Sezary Syndrome. Hematology 2024; 29:2366631. [PMID: 38975808 DOI: 10.1080/16078454.2024.2366631] [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: 01/13/2024] [Accepted: 05/30/2024] [Indexed: 07/09/2024] Open
Abstract
Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs.Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023.Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, β2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival.Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.
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Affiliation(s)
- Zhuo-Fan Xu
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China
- School of Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Hongyun Chen
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China
| | - Yuehua Liu
- Department of Dermatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China
| | - Wei Zhang
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China
| | - Hongzhong Jin
- Department of Dermatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China
| | - Jie Liu
- Department of Dermatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China
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Jung JM, Moon IJ, Lee WJ, Won CH, Chang SE, Lee MW. Clinically assessed mycosis fungoides tumor burden index as a prognostic marker in tumor-stage mycosis fungoides: a retrospective cohort study. Arch Dermatol Res 2024; 317:42. [PMID: 39576358 DOI: 10.1007/s00403-024-03496-x] [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: 06/03/2024] [Revised: 09/10/2024] [Accepted: 10/22/2024] [Indexed: 11/24/2024]
Abstract
Prognostic markers are needed for tumor-stage mycosis fungoides (MF) because of their variable prognosis. The objectives of this study were to explore prognostic markers for tumor-stage MF and assess the prognostic significance of clinically assessed MF tumor burden index (MTBI). MTBI was devised to consider the tumor size ≥ 2 cm, number ≥ 5, ulcers, and body surface area ≥ 50%. The prognostic value of MTBI and other potential markers derived from blood tests and skin biopsy were evaluated retrospectively using a tertiary medical center database. We included 38 cases of tumor-stage MF. The mean age was 52.1 years, and the male-to-female ratio was 2.5:1. In multivariable analysis, MTBI ≥ 3 (adjusted hazard ratio, 9.41; 95% confidence interval, 1.13-78.15) was significantly associated with worse disease-specific survival. Ulcers were the only MTBI constituent significantly associated with survival. Among other markers, elevated lactate dehydrogenase level was associated with a worse disease-specific survival. Neutrophil-lymphocyte-ratio, pan-inflammation-value, CD30 positivity, Ki-67 index, large cell transformation, and monoclonal T-cell receptor gene rearrangement were not associated with prognosis. In conclusion, MTBI is useful and promising prognostic marker for tumor-stage MF.
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Affiliation(s)
- Joon Min Jung
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea
| | - Ik Jun Moon
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea
| | - Woo Jin Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea
| | - Chong Hyun Won
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea
| | - Sung Eun Chang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea
| | - Mi Woo Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea.
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İsmail Mendi B, Şanlı H, Insel MA, Bayındır Aydemir B, Atak MF. Predicting Prognosis of Early-Stage Mycosis Fungoides with Utilization of Machine Learning. Life (Basel) 2024; 14:1371. [PMID: 39598170 PMCID: PMC11595863 DOI: 10.3390/life14111371] [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: 09/02/2024] [Revised: 10/17/2024] [Accepted: 10/23/2024] [Indexed: 11/29/2024] Open
Abstract
Mycosis fungoides (MF) is the most prevalent type of cutaneous T cell lymphomas. Studies on the prognosis of MF are limited, and no research exists on the potential of artificial intelligence to predict MF prognosis. This study aimed to compare the predictive capabilities of various machine learning (ML) algorithms in predicting progression, treatment response, and relapse and to assess their predictive power against that of the Cox proportional hazards (CPH) model in patients with early-stage MF. The data of patients aged 18 years and over who were diagnosed with early-stage MF at Ankara University Faculty of Medicine Hospital from 2006 to 2024 were retrospectively reviewed. ML algorithms were utilized to predict complete response, relapse, and disease progression using patient data. Of the 185 patients, 94 (50.8%) were female, and 91 (49.2%) were male. Complete response was observed in 114 patients (61.6%), while relapse and progression occurred in 69 (37.3%) and 54 (29.2%) patients, respectively. For predicting progression, the Support Vector Machine (SVM) algorithm demonstrated the highest success rate, with an accuracy of 75%, outperforming the CPH model (C-index: 0.652 for SVM vs. 0.501 for CPH). The most successful model for predicting complete response was the Ensemble model, with an accuracy of 68.89%, surpassing the CPH model (C-index: 0.662 for the Ensemble model vs. 0.543 for CPH). For predicting relapse, the decision tree classifier showed the highest performance, with an accuracy of 78.17%, outperforming the CPH model (C-index: 0.782 for the decision tree classifier vs. 0.505 for CPH). The results suggest that ML algorithms may be useful in predicting prognosis in early-stage MF patients.
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Affiliation(s)
- Banu İsmail Mendi
- Department of Dermatology, Niğde Ömer Halisdemir University Training and Research Hospital, Niğde 51000, Türkiye
| | - Hatice Şanlı
- Department of Dermatology, Faculty of Medicine, Ankara University, Ankara 06620, Türkiye; (H.Ş.); (B.B.A.)
| | - Mert Akın Insel
- Department of Chemical Engineering, Yıldız Technical University, İstanbul 34220, Türkiye;
| | - Beliz Bayındır Aydemir
- Department of Dermatology, Faculty of Medicine, Ankara University, Ankara 06620, Türkiye; (H.Ş.); (B.B.A.)
| | - Mehmet Fatih Atak
- Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA;
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Weiner DM, Rook AH. Cutaneous T-cell Lymphoma. Hematol Oncol Clin North Am 2024; 38:1087-1110. [PMID: 39079789 DOI: 10.1016/j.hoc.2024.05.012] [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: 09/03/2024]
Abstract
Cutaneous T-cell lymphoma is a group of non-Hodgkin T-cell lymphomas that develop in and affect the skin but can potentially spread to other organs. There are many subtypes, the most common of which are mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary cutaneous anaplastic large cell lymphoma. Cutaneous lymphoma is a common cause of recalcitrant chronic skin rash and notoriously mimics other dermatologic and hematologic conditions, often resulting in diagnostic delays of months to years. This review provides an introduction to cutaneous T-cell lymphoma, with a primary focus on the clinical presentation, diagnosis, immunopathogenesis, and management of the condition.
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Affiliation(s)
- David M Weiner
- Department of Dermatology, Johns Hopkins University School of Medicine, 601 North Caroline Street, 8th Floor, Baltimore, MD 21287, USA.
| | - Alain H Rook
- Department of Dermatology, Cutaneous Lymphoma Program, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, 1st Floor, Philadelphia, PA 19104, USA
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Atci T, Ozturk Sari S, Buyukbabani N, Besisik S, Baykal C. Evaluation of the prognostic significance of clinical features of tumoral lesions in an extensive series of mycosis fungoides. Int J Dermatol 2024; 63:1404-1413. [PMID: 38440839 DOI: 10.1111/ijd.17120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 01/31/2024] [Accepted: 02/19/2024] [Indexed: 03/06/2024]
Abstract
BACKGROUND Tumors indicating the advanced stage of mycosis fungoides (MF) have a rich clinical spectrum. Although it is known that the prognosis of MF generally worsens following the development of tumors, some cases may have a relatively indolent course, and the role of clinical characteristics regarding prognosis has still not been well understood. METHODS MF patients were retrospectively evaluated regarding the development of tumors. Besides demographic characteristics, data of the subtype and stage of the disease were recorded. The clinical features of tumors, including number (<5, 5-10, 11-20, or >20), location, dimension (diameter of ≥5 cm), presence of ulceration, and surrounding inflammation, were noted. Univariate and multivariate analyses evaluated the relationship between overall survival (OS) with demographic and clinical features. RESULTS Among 730 consecutive MF patients, tumors developed in 8.2% (n = 60), of whom 46.7% were diagnosed with advanced-stage MF from the beginning. The most common subtype was folliculotropic MF (53.3%). Most patients (55%) had multiple tumors, and the most frequent localization was the trunk (71.7%). Most tumors presented as smooth-surfaced, indurated papules and/or nodules (70%), while others were reddish-purple, occasionally accompanied by ulceration (50%), perilesional inflammation (23.3%), and attaining large dimensions (25%). Mortality was recorded in 51.7% of patients, and the 5-year OS rate from the diagnosis of tumors was 49%. Independent poor prognostic factors for OS in multivariate analysis included older age at the time of diagnosis, presence of tumors at the initial MF diagnosis, presence of over 20 tumors, and the existence of large tumors. CONCLUSIONS Tumoral MF seen in older patients, the first diagnosis of MF in this stage, presenting with generalized and large tumors, seems to be a predictive factor for OS.
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Affiliation(s)
- Tugba Atci
- Department of Dermatology and Venereology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Sule Ozturk Sari
- Department of Pathology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Nesimi Buyukbabani
- Department of Pathology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
- Department of Pathology, Koc University Medical Faculty, Istanbul, Turkey
| | - Sevgi Besisik
- Department of Hematology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Can Baykal
- Department of Dermatology and Venereology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
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Moreno-Vílchez C, Servitje O, Íñiguez-Arroyo Ó, Muniesa C. Survival Analysis and Prognostic Factors in a Case Series of 148 Cutaneous T-Cell Lymphomas. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:766-772. [PMID: 38159841 DOI: 10.1016/j.ad.2023.12.002] [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: 10/17/2023] [Revised: 11/29/2023] [Accepted: 12/04/2023] [Indexed: 01/03/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Cutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. MATERIALS AND METHODS All cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. RESULTS A total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. CONCLUSIONS Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients' survival and was closely associated with tumor skin involvement and stage IIB.
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Affiliation(s)
- C Moreno-Vílchez
- Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, España
| | - O Servitje
- Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, España
| | - Ó Íñiguez-Arroyo
- Facultad de Medicina y Ciencias de la Salud, Campus Bellvitge, Universitat de Barcelona, Barcelona, España
| | - C Muniesa
- Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, España.
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10
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Moreno-Vílchez C, Servitje O, Íñiguez-Arroyo Ó, Muniesa C. [Translated article] Survival Analysis and Prognostic Factors in a Case Series of 148 Cutaneous T-Cell Lymphomas. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:T766-T772. [PMID: 38972577 DOI: 10.1016/j.ad.2024.07.006] [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: 10/17/2023] [Revised: 11/29/2023] [Accepted: 12/04/2023] [Indexed: 07/09/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Cutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. MATERIALS AND METHODS All cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. RESULTS A total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. CONCLUSIONS Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients' survival and was closely associated with tumor skin involvement and stage IIB.
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Affiliation(s)
- C Moreno-Vílchez
- Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain
| | - O Servitje
- Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain
| | - Ó Íñiguez-Arroyo
- Facultad de Medicina y Ciencias de la Salud, Campus Bellvitge, Universitat de Barcelona, Barcelona, Spain
| | - C Muniesa
- Servicio de Dermatología, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
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Frischhut N, Nguyen VA. A case report of refractory advanced-stage mycosis fungoides: successful treatment and improved patient quality of life with mogamulizumab. Ther Adv Hematol 2024; 15:20406207241260340. [PMID: 39091322 PMCID: PMC11292691 DOI: 10.1177/20406207241260340] [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: 05/03/2023] [Accepted: 05/10/2024] [Indexed: 08/04/2024] Open
Abstract
Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, is characterized by patches, plaques, and, in advanced stages, tumors and erythroderma. Early-stage MF may progress to advanced-stage disease in up to one-third of patients, conferring a worse prognosis and typically requiring systemic treatment for extracutaneous involvement. The most frequently reported signs and symptoms are pain, pruritus, scaling, and skin redness, with pruritus, the most bothersome symptom, exerting a profound impact on patients' health-related quality of life (HRQoL). These dermatologic signs and symptoms can overlap with those of other benign inflammatory dermatoses, such as eczema and psoriasis, and therefore, diagnostic delay is common in patients with MF. Moreover, identifying patients with features adversely affecting prognosis (e.g. large-cell transformation or folliculotropic variant) is a significant challenge. We report the case of a 75-year-old female patient who was misdiagnosed with eczema and then pityriasis rubra pilaris and consequently did not receive treatment for MF for 4 years. The patient was eventually correctly diagnosed with MF [stage IIIB (T4 N1 M0 B1)] in September 2018. The patient received several systemic treatments; however, she did not respond to or tolerate the treatments. Due to lack of treatment response, in July 2021, she was initiated on mogamulizumab, an anti-CC chemokine receptor 4 antibody with demonstrated effectiveness and licensed approval for adults with MF/Sézary syndrome who have received one or more prior systemic therapies. Treatment rapidly led to a complete response in blood after 1 week and in skin after 4 months. Mogamulizumab was well tolerated by the patient, who also reported a significant improvement in her HRQoL. After 1 year in complete response, mogamulizumab was discontinued. This case highlights the need for accurate and early diagnosis of MF to initiate disease-specific treatment and the importance of considering patient HRQoL when treating this condition.
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Affiliation(s)
- Nina Frischhut
- Department of Dermatology, Venereology, and Allergology, Medical University of Innsbruck, Innsbruck, Austria
| | - Van Anh Nguyen
- Department of Dermatology, Venereology, and Allergology, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria
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Chen JJ, Tokumori FC, Del Guzzo C, Kim J, Ruan J. Update on T-Cell Lymphoma Epidemiology. Curr Hematol Malig Rep 2024; 19:93-103. [PMID: 38451372 DOI: 10.1007/s11899-024-00727-w] [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] [Accepted: 01/31/2024] [Indexed: 03/08/2024]
Abstract
PURPOSE OF REVIEW T-cell lymphomas (TCLs) are a group of rare subtypes of non-Hodgkin lymphoma derived from mature T-lymphocytes. Recent updates in lymphoma classification based on the cell-of-origin pathogenesis have shed new light on TCL epidemiology and outcomes. Contemporary regional consortia and international studies, including those conducted recently in Asia and South America, have provided an updated delineation of the major subtypes across various global regions. RECENT FINDINGS Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), remains the most common subtype globally except in Asia, where extra-nodal NK-T cell lymphoma (ENKTL) has emerged as the most prevalent. Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype globally except in South America where its incidence falls behind adult T-cell leukemia/lymphoma (ATLL) and ENKTL. ALK-negative anaplastic large cell lymphoma (ALCL) has been recognized as the second most common subtype in some parts of South America. Studies on the newly classified breast implant-associated ALCL (BIA-ALCL) are beginning to reveal its distribution and risk factors. Deciphering the epidemiology of TCLs is a challenging endeavor due to the rarity of these entities and ongoing refinement in classification. Collaborative efforts on prospective registries based on the most current WHO classifications will help capture the true epidemiology of TCL subtypes to better focus resources for diagnostic, prognostic, and therapeutic efforts.
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MESH Headings
- Humans
- Lymphoma, T-Cell/epidemiology
- Lymphoma, T-Cell/diagnosis
- Lymphoma, T-Cell/therapy
- Lymphoma, T-Cell/pathology
- Incidence
- Lymphoma, T-Cell, Peripheral/epidemiology
- Lymphoma, T-Cell, Peripheral/therapy
- Lymphoma, T-Cell, Peripheral/diagnosis
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Affiliation(s)
- Jane J Chen
- Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Franco Castillo Tokumori
- Division of Hematology and Medical Oncology, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10065, USA
| | | | - Jeanyoung Kim
- Division of Dermatology, Weill Cornell Medicine, New York, NY, USA
| | - Jia Ruan
- Division of Hematology and Medical Oncology, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10065, USA.
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Kaya Terzi N. Decoding Early Mycosis Fungoides: Histopathologic and Immunohistochemical Clues. Cureus 2024; 16:e57545. [PMID: 38577165 PMCID: PMC10993093 DOI: 10.7759/cureus.57545] [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] [Accepted: 04/03/2024] [Indexed: 04/06/2024] Open
Abstract
INTRODUCTION Primary cutaneous lymphomas, notably mycosis fungoides (MF), present diagnostic challenges in recognizing early mycosis fungoides (eMF) due to their diverse clinical and histopathologic manifestations. The aim of our study was to use adjunctive histopathologic and immunohistochemical methods in eMF cases to make an early diagnosis and to facilitate differentiation from other dermatoses. METHODS This retrospective study analyzed 35 cases of eMF diagnosed at a single center. Demographic and clinicopathologic data were collected, and histopathologic features were assessed. Comparative analyses were conducted with conditions mimicking eMF, including large plaque parapsoriasis (LPP), psoriasis, and chronic dermatitis. Immunohistochemistry for T-cell markers (CD3, CD4, CD8, CD2, CD7) was performed. RESULTS With the scoring we applied in our study, a sensitivity of 91.43% (95% CI; 76.94% to 98.20%) and specificity of 85.71% (95% CI; 69.74% to 95.19%) for distinguishing eMF from LPP. Epidermotropism emerged as a crucial histopathologic marker, with a notable absence in most cases of cutaneous dermatitis (81.6% and 80% for CD and psoriasis, respectively) (P < 0.001). Immunohistochemistry revealed a T-helper phenotype (CD4+/CD8-) in the majority of eMF cases (78.1%), while CD4+/CD8+ and CD8+/CD4- patterns were less common (28.5% and 8.5%, respectively). CONCLUSION This study underscores the complexities in distinguishing eMF from inflammatory skin diseases, advocating for a comprehensive diagnostic approach.
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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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15
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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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Jung JM, Cho HS, Kim GH, Won CH, Chang SE, Park CS, Lee MW, Lee WJ. Psoriasiform mycosis fungoides: a clinical and prognostic retrospective cohort study. Br J Dermatol 2024; 190:432-434. [PMID: 37936328 DOI: 10.1093/bjd/ljad423] [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: 01/17/2023] [Revised: 07/20/2023] [Accepted: 11/15/2023] [Indexed: 11/09/2023]
Abstract
The psoriasiform manifestation of mycosis fungoides (MF) was identified in 17.5% of patients in this study. Psoriasiform MF had a shorter prediagnosis period than the other subtypes. Psoriasiform MF was associated with advanced stage, lymph node involvement and large cell transformation, and was thus also associated with poor survival.
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Affiliation(s)
| | | | | | | | | | - Chan Sik Park
- Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Goyal A, Foss F. Allogeneic transplantation and cellular therapies in cutaneous T-cell lymphoma. Expert Rev Anticancer Ther 2024; 24:41-58. [PMID: 38224371 DOI: 10.1080/14737140.2024.2305356] [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: 07/21/2023] [Accepted: 01/10/2024] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease control, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option for advanced stage MF and SS. CAR T-cell therapy is a promising new avenue for treatment. AREAS COVERED In this review, we discuss the evidence supporting the use of allo-HSCT for the treatment of MF/SS, including disease status at the time of transplant, conditioning regimen, total body irradiation (TBI), and donor lymphocyte infusion (DLI). We also address the potential role for CAR T-cell therapy in CTCL. EXPERT OPINION Allo-HSCT is an effective treatment for patients with advanced MF and SS. However, significant research is required to determine optimal treatment protocols. Data support the use of reduced-intensity conditioning regimens and suggests that the use of TBI for debulking of skin disease may result in more durable remissions. Donor lymphocyte infusions (DLI) appear to be particularly effective in inducing complete remission in MF/SS patients with relapsed or residual disease. Challenges with CAR-T therapies in T-cell lymphoma include T-cell fratricide due to shared antigens on malignant and nonmalignant T-cells, penetrance into the skin compartment, and CAR-T cell persistence.
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Affiliation(s)
- Amrita Goyal
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Francine Foss
- Department of Hematology/Oncology, Yale School of Medicine, New Haven, Connecticut, USA
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Lachance M, Thibeault MM. Clinical characteristics, initial treatment, and prognosis of mycosis fungoides and Sézary syndrome: A retrospective, single-center study at the Centre Hospitalier Universitaire of Quebec. Ann Dermatol Venereol 2023; 150:276-280. [PMID: 37777355 DOI: 10.1016/j.annder.2023.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 05/03/2023] [Accepted: 06/26/2023] [Indexed: 10/02/2023]
Affiliation(s)
- M Lachance
- Department of Dermatology, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada.
| | - M-M Thibeault
- Department of Dermatology, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada
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Titou H, Bouhamidi A. Epidemiology and prognostic factors of 114 patients with mycosis fungoides in a Moroccan cohort: a 29-year review. Clin Exp Med 2023; 23:3751-3758. [PMID: 37029872 DOI: 10.1007/s10238-023-01056-7] [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: 01/14/2023] [Accepted: 03/22/2023] [Indexed: 04/09/2023]
Abstract
Limited data regarding survival of Moroccan patients with mycosis fungoides (MF). To evaluate the clinical profile and long-term outcomes of these patients. A retrospective review of 114 MF cases diagnosed from 1993 to 2022 who were followed up for more than 6 months of diagnosis was performed. Of 114 patients, 71.9% were male and the median age at diagnosis was 56 years. Approximately 64 and 36% of the patients had an early stage and advanced stage, respectively. Median follow-up duration was 56 months, and median duration of symptoms before diagnosis was 31 months. Various subtypes were observed, including mycosis fungoides folliculotropic (12.3%), poikilodermatous (11.4%), and palmaris et plantaris MF (5.3%). The 10-year overall survival was 89% in early-stage patients and 48.8% in advanced-stage patients. Complete response to treatment occurred in 45.6%, stable disease in 16.7% and disease progression in 7.9% of patients. Older age of > 60 years, higher T-stage (T3/T4) and advanced-stage MF were statistically significant in predicting poorer outcomes in MF. Despite delay in diagnosis, most cases of MF in Morocco were diagnosed in early stages. We observed a high proportion of classic MF and favorable prognosis.
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Affiliation(s)
- Hicham Titou
- Department of Dermatology-Venereology, Avicenne Military Hospital, Al Mouquaouama Avenue, 40000, Marrakech, Morocco.
| | - Ahmed Bouhamidi
- Department of Dermatology-Venereology, Avicenne Military Hospital, Al Mouquaouama Avenue, 40000, Marrakech, Morocco
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20
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Tang H, Matsumoto N, Foss F, Xu M, Ahmed A. Clinicopathologic Features of Cutaneous T-Cell Lymphomas With Extracutaneous Metastasis: A Case Series. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:e405-e410. [PMID: 37659965 DOI: 10.1016/j.clml.2023.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/29/2023] [Accepted: 08/06/2023] [Indexed: 09/04/2023]
Abstract
BACKGROUND In advanced stages, Cutaneous T-cell lymphomas (CTCL) can metastasize to extracutaneous regions. CTCL with metastasis exhibits unique clinicopathologic characteristics. PATIENTS AND METHODS This study collected 35 cases of primary CTCL with extracutaneous metastasis from a single institution over a period of 20 years. Clinicopathologic features including demographics, CD30 expression, large cell transformation, metastatic sites, T-cell receptor clonality studies and survival data were analyzed. RESULTS The study identified various CTCL entities including mycosis fungoides (MF), Sezary syndrome (SS), cutaneous anaplastic large cell lymphoma (C-ALCL), and primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS). Limited data showed that metastasis can be independent of large cell transformation and/or CD30 expression. Lymph nodes were the most common site of metastasis, followed by the bone marrow. Oropharyngeal metastasis is likely to accompany visceral organ or brain metastasis (P = .049). MF had a longer interval to metastasis than SS (P = .038). Patients with lymph node only metastasis have better survival than patients with metastasis to other sites (P = .012). CONCLUSION To the best of our knowledge, there are limited studies analyzing the clinicopathologic features of different CTCL entities with metastasis as a single population. This research provides valuable insights into the unique characteristics of metastatic CTCL.
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Affiliation(s)
- Haiming Tang
- Department of Pathology, Yale School of Medicine, New Haven, CT
| | - Nana Matsumoto
- Department of Pathology, Brigham and Women's Hospital, Boston, MA
| | - Francine Foss
- Department of Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT
| | - Mina Xu
- Department of Pathology, Yale School of Medicine, New Haven, CT
| | - Aadil Ahmed
- Department of Pathology, Rush University Medical Center, Chicago, IL.
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Stuver R, Geller S. Advances in the treatment of mycoses fungoides and Sézary syndrome: a narrative update in skin-directed therapies and immune-based treatments. Front Immunol 2023; 14:1284045. [PMID: 37868986 PMCID: PMC10585160 DOI: 10.3389/fimmu.2023.1284045] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 09/25/2023] [Indexed: 10/24/2023] Open
Abstract
Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials.
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Affiliation(s)
- Robert Stuver
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Shamir Geller
- Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
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Hawkins N, Muszbek N, Evans R, McNamara L, Jones T. Overall survival in the UK in mycosis fungoides or Sézary syndrome cutaneous T-cell lymphoma: comparative effectiveness of mogamulizumab versus current standard of care. J Comp Eff Res 2023; 12:e230017. [PMID: 37642410 PMCID: PMC10690402 DOI: 10.57264/cer-2023-0017] [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: 02/03/2023] [Accepted: 08/02/2023] [Indexed: 08/31/2023] Open
Abstract
Aim: Due to extensive treatment switching in the MAVORIC trial, lack of UK regulatory licence for the comparator, overall survival (OS) with mogamulizumab was compared with patients with previously treated advanced mycosis fungoides/Sézary syndrome (MF/SS) in real-world setting. Design, setting & participants: Data were from the Hospital Episode Statistics database (all patients in NHS secondary care system in 2009-2019). Patients were selected according to trial inclusion criteria, then trial and HES samples were matched on selected variables with significant imbalance. Outcomes: The analysis indicated significant improvement in OS for mogamulizumab treatment compared with UK clinical practice (hazard ratio: 0.36, 95% CI: 0.24, 0.53). Conclusion: Results suggest an OS advantage for patients with advanced MF/SS treated with mogamulizumab in MAVORIC trial compared with UK clinical practice.
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Affiliation(s)
| | | | | | - Linda McNamara
- Kyowa Kirin, Payor Value and Patient Access, Marlow, SL7 1HZ, UK
| | - Trefor Jones
- Kyowa Kirin, Payor Value and Patient Access, Marlow, SL7 1HZ, UK
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Chen Z, Lin Y, Qin Y, Qu H, Zhang Q, Li Y, Wen Y, Sun J, Tu P, Gao P, Wang Y. Prognostic Factors and Survival Outcomes Among Patients With Mycosis Fungoides in China: A 12-Year Review. JAMA Dermatol 2023; 159:1059-1067. [PMID: 37585188 PMCID: PMC10433139 DOI: 10.1001/jamadermatol.2023.2634] [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: 01/27/2023] [Accepted: 06/14/2023] [Indexed: 08/17/2023]
Abstract
Importance There are limited prognostic statistics and data available on survival outcomes for patients with mycosis fungoides (MF) in Asia. Objective To determine the prognostic factors and survival outcomes of patients with MF among a cohort in China. Design, Setting, and Participants This was a retrospective cohort study of patients with MF who received treatment at a tertiary referral center for skin lymphoma (Peking University First Hospital, Beijing, China) from August 1, 2009, to August 31, 2021. Data were analyzed from September 1, 2021, to December 31, 2022. Main Outcomes and Measures Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS); for prognostic factors, hazard ratios (HRs), and adjusted HRs (aHRs; adjusted for sex, age, and overall TNMB [tumor, node, metastasis, blood] stage) determined using the Cox proportional hazards model. Results The study cohort comprised 461 patients with MF (median [range] age at diagnosis, 46 [5-87] years; 275 [59.7%] men and 186 [40.3%] women; 461 [100%] Chinese). The overall 5-year rate was 82.2% for OS, 83.5% for DSS, and 79.6% for PFS. Stage-specific 5-year OS rates were 95.7% for stage IA, 93.2% for IB, 95.7% for IIA, 70.1% for IIB, 55.3% for III, and 23.6% for IV. Compared with a UK cohort, our Chinese cohort had a younger median age at diagnosis (46 years vs 54 years) and a more favorable 5-year OS (82.2% vs 75.0%); however, after adjusting for age, the discrepancy in the 5-year OS rate was diminished (77.3% vs 76.4%). Cox models revealed that unfavorable predictors of OS, PFS, and DSS, respectively, were: age older than 60 years (aHR [95% CI], 2.25 [1.28-3.96]; 2.09 [1.16-3.76]; 2.27 [1.39-3.72]); advanced TNMB stage; advanced overall stage; large-cell transformation (aHR [95% CI], 2.16 [1.17-3.99]; 2.29 [1.21-4.33]; 2.21 [1.26-3.86]); and elevated lactate dehydrogenase levels (aHR [95% CI], 3.92 [1.64-9.36]; 4.77 [1.86-12.22]; 5.05 [2.23-11.42]). Biological sex and plaque lesion type were not associated with prognosis among this study cohort. Conclusion and Relevance The findings of this retrospective cohort study of patients with MF in China suggest that Asian patients are diagnosed at a younger age and have a higher 5-year OS compared with patients of other races in studies in other countries (predominantly White). Prognostic factors were similar to those of previous studies, except for patient sex and plaque lesion type.
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Affiliation(s)
- 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
- National Medical Products Administration, Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Yuwei Lin
- Peking University Clinical Research Institute, Peking University, Beijing, China
| | - 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
- National Medical Products Administration, Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Hui Qu
- 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
- National Medical Products Administration, 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
- National Medical Products Administration, Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Jingru Sun
- 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
- National Medical Products Administration, 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
- National Medical Products Administration, Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
| | - Pei Gao
- Peking University Clinical Research Institute, Peking University, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 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
- National Medical Products Administration, Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
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Avery J, Kim SR, Cheng W, Foss F, Girardi M. FISH Panel for Leukemic Cutaneous T-Cell Lymphoma: Extended Patient Cohort Correlation with Blood Involvement and Clinical Outcomes. JID INNOVATIONS 2023; 3:100212. [PMID: 37674691 PMCID: PMC10477749 DOI: 10.1016/j.xjidi.2023.100212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 04/20/2023] [Accepted: 04/24/2023] [Indexed: 09/08/2023] Open
Abstract
The genomic basis of cutaneous T-cell lymphoma has been characterized by gene copy number alterations and genomic sequencing, but there are few clinical tests that are being widely used to inform the diagnosis and prognosis of leukemic cutaneous T-cell lymphoma that may arise as a progression from mycosis fungoides or de novo as Sézary syndrome. An 11-gene FISH panel of TP53, RB1, DNMT3A, FAS, ZEB1, ARID1A, ATM, and CDKN2A deletions and MYC, signal transducer and activator of transcription gene (STAT)3/5B, and CARD11 amplifications was previously found to encapsulate >95% of gene copy number variations in leukemic cutaneous T-cell lymphoma. Through a retrospective analysis of patients with leukemic cutaneous T-cell lymphoma seen at the Yale Cancer Center from 2014 to 2020, we gathered the relevant genes as they became available and correlated them to factors with prognostic relevance as a proof of concept to show the potential utility in further developing a limited gene panel for prognosis. In this study, we show that the abnormal FISH results show an association with clinically relevant factors (blood stage, CD4:8 ratio, and percentage blood involvement) and have a nonsignificant statistical trend (>90%) toward correlation with overall survival. In addition, the previous cost-effective panels were signal transducer and activator of transcription (STAT)3/5B, MYC, TP53, and ARID1A. We now suggest adding RB1 and ZEB1 on the basis of our findings.
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Affiliation(s)
- Jonathan Avery
- Department of Internal Medicine, University of Washington, Seattle, Washington, USA
| | - Sa Rang Kim
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Wei Cheng
- Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA
| | - Francine Foss
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Michael Girardi
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
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Muszbek N, Remak E, Xin Q, McNamara L, Jones T. Cost-utility analysis of mogamulizumab in advanced mycosis fungoides and Sézary syndrome cutaneous T-cell lymphoma. J Comp Eff Res 2023; 12:CER. [PMID: 37338181 PMCID: PMC10508303 DOI: 10.57264/cer-2023-0028] [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: 02/21/2023] [Accepted: 05/22/2023] [Indexed: 06/21/2023] Open
Abstract
Aim: This study assessed the cost-utility of mogamulizumab, a novel monoclonal antibody, versus established clinical management (ECM) in UK patients in previously treated advanced mycosis fungoides (MF)/Sézary syndrome (SS). Materials & methods: Lifetime partitioned survival model based on overall survival, next treatment-free survival and the use of allogeneic stem cell transplant was developed. Inputs were from the pivotal MAVORIC trial, real-world evidence and published literature. Extensive sensitivity analyses were conducted. Results: Discounted incremental quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio were 3.08, £86,998 and £28,233. Results were most sensitive to the survival extrapolations, utilities and costs after loss of disease control. Conclusion: Mogamulizumab is a cost-effective alternative to ECM in UK patients with previously treated advanced MF/SS.
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Wilkinson AJ, Nader ME, Roberts D, Duvic M, Gunther JR, Dabaja BS, Gidley PW. Survival Outcomes of Patients with Mycosis Fungoides Involving the External Ear and Ear Canal. Laryngoscope 2023; 133:1486-1491. [PMID: 36054317 PMCID: PMC9971327 DOI: 10.1002/lary.30377] [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: 04/19/2022] [Revised: 07/19/2022] [Accepted: 08/09/2022] [Indexed: 11/09/2022]
Abstract
OBJECTIVES/HYPOTHESIS Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear. STUDY DESIGN Retrospective analysis. METHODS We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021. RESULTS We report the largest series of patients with MF involving the external ear and EAC. Of the 40 patients included in this study, 17 presented with Mycosis Fungoides in the otologic region (MFO). Of these 17 MFO patients, 2/17 had involvement of the external ear only, 3/17 of the EAC only, 11/17 of both the external ear and EAC, and 1/17 of the periauricular skin. Of note, 11/14 (79%) patients presenting with EAC disease died compared to11/26 (42%) of patients without involvement. In addition, eight of the 13 (62%) patients with external ear involvement died compared to 14/27 (52%) of patients without involvement. Ear canal involvement was associated with a statistically significant shorter overall survival duration in patients with MF (p = 0.03). Furthermore, disease in the EAC was found to have a hazard ratio value of 2.565 (CI 1.102-5.970). CONCLUSIONS Involvement of the EAC by MF portends a poor prognosis. This finding highlights the need for a more in-depth otologic evaluation of patients with MF. LEVEL OF EVIDENCE 4 Laryngoscope, 133:1486-1491, 2023.
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Affiliation(s)
| | - Marc-Elie Nader
- Department of Head and Neck Surgery, MD Anderson Cancer Center
| | - Dianna Roberts
- Department of Head and Neck Surgery, MD Anderson Cancer Center
| | | | | | | | - Paul W Gidley
- Department of Head and Neck Surgery, MD Anderson Cancer Center
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27
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Quaglino P, Scarisbrick J, Roccuzzo G, Abeldano A, Battistella M, McCormack C, Cowan R, Cozzio A, Cury-Martins J, Enz P, Geskin L, Guenova E, Kim YH, Knobler R, Litvinov IV, Miyagaki T, Molgo M, Nicolay J, Papadavid E, Pinter-Brown L, Pujol Vallverdu R, Querfeld C, Ortiz-Romero P, Stadler R, Vermeer MH, Bagot M, Hodak E. Identifying unmet needs and challenges in the definition of a plaque in mycosis fungoides: An EORTC-CLTG/ISCL survey. J Eur Acad Dermatol Venereol 2023; 37:680-688. [PMID: 36606565 DOI: 10.1111/jdv.18852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 12/13/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND Consensus about the definition and classification of 'plaque' in mycosis fungoides is lacking. OBJECTIVES To delineate a comprehensive view on how the 'plaque' entity is defined and managed in clinical practice; to evaluate whether the current positioning of plaques in the TNMB classification is adequate. METHODS A 12-item survey was circulated within a selected panel of 22 experts (pathologists, dermatologists, haematologists and oncologists), members of the EORTC and International Society for Cutaneous Lymphoma. The questionnaire discussed clinical and histopathological definitions of plaques and its relationship with staging and treatment. RESULTS Total consensus and very high agreement rates were reached in 33.3% of questions, as all panellists regularly check for the presence of plaques, agree to evaluate the presence of plaques as a potential separate T class, and concur on the important distinction between plaque and patch for the management of early-stage MF. High agreement was reached in 41.7% of questions, since more than 50% of the responders use Olsen's definition of plaque, recommend the distinction between thin/thick plaques, and agree on performing a biopsy on the most infiltrated/indurated lesion. High divergence rates (25%) were reported regarding the possibility of a clinically based distinction between thin and thick plaques and the role of histopathology to plaque definition. CONCLUSIONS The definition of 'plaque' is commonly perceived as a clinical entity and its integration with histopathological features is generally reserved to specific cases. To date, no consensus is achieved as for the exact definition of thin and thick plaques and current positioning of plaques within the TNMB system is considered clinically inadequate. Prospective studies evaluating the role of histopathological parameters and other biomarkers, as well as promising diagnostic tools, such as US/RM imaging and high-throughput blood sequencing, are much needed to fully integrate current clinical definitions with more objective parameters.
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Affiliation(s)
- Pietro Quaglino
- Dermatologic Clinic, Department of Medical Sciences, University of Torino, Torino, Italy
| | | | - Gabriele Roccuzzo
- Dermatologic Clinic, Department of Medical Sciences, University of Torino, Torino, Italy
| | - Alejandra Abeldano
- Hospital Gral. de Agudos Dr. C. Argerich, Ciudad de Buenos Aires, Buenos Aires, Argentina
| | - Maxime Battistella
- Université Paris Cité, INSERM U976 HIPI, Paris, France.,Department of Pathology, AP-HP Saint-Louis Hospital, Paris, France
| | - Chris McCormack
- Surgical Oncology Department, Peter MacCallum Cancer Centre, Parkvile, Victoria, Australia
| | - Richard Cowan
- Department of Clinical Oncology, The Christie Hospital, Manchester, UK
| | - Antonio Cozzio
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Jade Cury-Martins
- Department of Dermatology, University of São Paulo Medical School, São Paulo, Brazil
| | - Paula Enz
- Hospital Italiano de Buenos Aires, Ciudad de Buenos Aires, Buenos Aires, Argentina
| | - Larisa Geskin
- Columbia University Medical Center, New York, New York, USA
| | | | - Youn H Kim
- Stanford Cancer Institute, Stanford, California, USA
| | - Robert Knobler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Ivan V Litvinov
- Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada
| | - Tomomitsu Miyagaki
- Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Montserrat Molgo
- Department of Dermatology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jan Nicolay
- Department of Dermatology, University Medical Center Mannheim, Mannheim, Germany
| | - Evangelina Papadavid
- 2nd Department of Dermatology and Venereology, ATTIKON University Hospital, Athens, Greece
| | | | | | | | - Pablo Ortiz-Romero
- Hospital 12 de Octubre, Institute I+12, CIBERONC, Medical School, Universidad Complutense, Madrid, Spain
| | - Rudolf Stadler
- University Hospitals of the Ruhr-University of Bochum, Minden, Germany
| | - Maarten H Vermeer
- Department of Dermatology, Leiden University Medical Center, RC Leiden, The Netherlands
| | | | - Emmilia Hodak
- Rabin Medical Center, Beilinson Hospital, Petah Tiqva, Israel
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Atilla PA, Atilla E. Are we there yet? cellular therapies for cutaneous T cell lymphoma. Curr Res Transl Med 2023; 71:103390. [PMID: 37062252 DOI: 10.1016/j.retram.2023.103390] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 03/08/2023] [Accepted: 04/04/2023] [Indexed: 04/18/2023]
Abstract
Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of skin-involved T-cell non-Hodgkin lymphoma which Mycosis Fungoides and Sezary Syndrome are the most common variants. Despite considerable progress in distinguishing the pathophysiology, the treatment options are still limited for advanced-stage disease. Recent approval of novel agents such as vorinostat, brentuximab vedotin and mogamulizumab paved a way. Allogeneic hematopoietic stem cell transplantation has been shown to be a feasible option in selected advanced-stage CTCL patients. Chimeric antigen receptor (CAR) T cells have been promising for the treatment of B-cell tumors and have been approved for second-line treatment in non-Hodgkin's lymphoma. Although several obstacles still need to be addressed, CAR T cell treatment for CTCLs seems not far off. This review discusses new discoveries in pathophysiology, the state of cellular therapies in current practice, challenges for cellular treatment in advanced CTCL, and how to overcome these challenges.
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Affiliation(s)
- Pinar Ataca Atilla
- Ankara University Stem Cell Institute, Ankara, Turkey; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA
| | - Erden Atilla
- Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA; Genyo Centre for Genomics and Oncological Research, Genomic Medicine Department, Pfizer/University of Gradana/Andalusian Regional Government, Health Sciences Technnology Park, Granada, Spain.
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Vitiello P, Sagnelli C, Ronchi A, Franco R, Caccavale S, Mottola M, Pastore F, Argenziano G, Creta M, Calogero A, Fiorelli A, Casale B, Sica A. Multidisciplinary Approach to the Diagnosis and Therapy of Mycosis Fungoides. Healthcare (Basel) 2023; 11:healthcare11040614. [PMID: 36833148 PMCID: PMC9957453 DOI: 10.3390/healthcare11040614] [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: 01/03/2023] [Revised: 02/10/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023] Open
Abstract
Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.
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Affiliation(s)
- Paola Vitiello
- Dermatology Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
- Correspondence: ; Tel.: +39-39-3810-7860
| | - Andrea Ronchi
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Stefano Caccavale
- Dermatology Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Maria Mottola
- Department of Heart Surgery and Transplantations, AORN Dei Colli-V Monaldi, 80131 Naples, Italy
| | | | - Giuseppe Argenziano
- Dermatology Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
| | - Armando Calogero
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Alfonso Fiorelli
- Thoracic Surgery Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Beniamino Casale
- Department of Pneumology and Tisiology, AO Dei Colli-V. Monaldi, 80131 Naples, Italy
| | - Antonello Sica
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
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Cutaneous lymphomas—fast facts about an orphan disease—a short review. MEMO - MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2023. [DOI: 10.1007/s12254-022-00863-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
SummaryCutaneous lymphomas are a rare group of primary skin lymphoproliferative disorders, divided into T and B cell lymphomas. They differ substantially in clinical course and therapy. The two main subtypes of primary cutaneous T‑cell lymphomas include mycosis fungoides, which is the most common, and Sézary syndrome, the rare leukemic variant. Skin lesions seen in mycosis fungoides patients are erythematous patches, plaques, or tumors. Most patients remain at patch/plaque (early) stage, while some progress to tumor (advanced) stage during their clinical course. Sézary syndrome is characterized by erythroderma and involvement of lymph nodes and the peripheral blood. Treatment is dependent on the disease stage. Therapeutic options include skin-directed and systemic therapies. In localized, early stage mycosis fungoides, prognosis is usually good which changes in advanced stages. Significant progress has been made in recent years in the clinical management of progressive or relapsed cutaneous T‑cell lymphomas by the approval of new targeted therapies. Although there are no curative treatment options apart from allogeneic transplantation, response rates are often encouraging, in particular when using combination therapies. Primary cutaneous B cell lymphomas are rare and three main subtypes are recognized: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B‑cell lymphoma, leg type. An accurate diagnosis of the subtype is important for therapeutic management. The most common clinical presentations are red-to-violaceous cutaneous nodules and papules. Primary cutaneous marginal and follicle center lymphoma have excellent 5‑year survival rates of 95–99%.
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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: 0] [Impact Index Per Article: 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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Lombardi CV, Glosser LD, Hopper W, Veria S, Awad MT, Garg A. Erythrodermic mycosis fungoides with large cell transformation: An unusual and complicated case. SAGE Open Med Case Rep 2022; 10:2050313X221131163. [PMID: 36313267 PMCID: PMC9608024 DOI: 10.1177/2050313x221131163] [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: 02/26/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022] Open
Abstract
Mycosis fungoides is the most common cutaneous T-cell lymphoma. It presents a diagnostic challenge due to resemblance with many other dermatologic conditions. The disease typically follows a progression from patches to plaques to skin-based tumors with potential for visceral involvement. Diagnosis is made by clinical presentation and histology. When early diagnosis is made, there is an estimated 88% five-year survival. This report details a 60-year-old Black man diagnosed with stage IIIA mycosis fungoides with a severe degree of cutaneous involvement. This case is unique due to the aggressive large cell transformation and rapid progression to death within 18 months of diagnosis. We highlight the challenge of diagnosing, treating, and monitoring the therapeutic response of mycosis fungoides. Finally, this case calls for a multi-disciplinary approach to treatment and to include mycosis fungoides on the differential diagnosis for patients presenting with a variety of vague, recurrent cutaneous symptoms, especially with patchy dyspigmentation or plaques.
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Affiliation(s)
- Conner V Lombardi
- College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA
| | - Logan D Glosser
- College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA
| | - Wade Hopper
- Edward via College of Osteopathic Medicine, Spartanburg, SC, USA
| | - Spiro Veria
- College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA
| | - Mohammed T Awad
- Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA
| | - Anu Garg
- Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA
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van Santen S, Zoutman WH, de Masson A, Quint KD, Willemze R, Gerard N, Teague JE, Kupper TS, Clark RA, Tensen CP, Vermeer MH. Tumor Clone Frequency Calculation Using High-Throughput Sequencing of the TCRβ Gene in Patients with Folliculotropic Mycosis Fungoides. J Invest Dermatol 2022; 142:2544-2546.e2. [PMID: 35304252 PMCID: PMC11167127 DOI: 10.1016/j.jid.2021.11.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 11/21/2021] [Accepted: 11/23/2021] [Indexed: 11/25/2022]
Affiliation(s)
- Suzanne van Santen
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Willem H Zoutman
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Adèle de Masson
- Department of Dermatology, INSERM U976, Saint-Louis Hospital, University of Paris, Paris, France
| | - Koen D Quint
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Nega Gerard
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cutaneous (Skin) Cancer Treatment Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jessica E Teague
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cutaneous (Skin) Cancer Treatment Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Thomas S Kupper
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cutaneous (Skin) Cancer Treatment Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Rachael A Clark
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cutaneous (Skin) Cancer Treatment Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Cornelis P Tensen
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Maarten H Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
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Kim EJ, Mangold AR, DeSimone JA, Wong HK, Seminario-Vidal L, Guitart J, Appel J, Geskin L, Lain E, Korman NJ, Zeitouni N, Nikbakht N, Dawes K, Akilov O, Carter J, Shinohara M, Kuzel TM, Piette W, Bhatia N, Musiek A, Pariser D, Kim YH, Elston D, Boh E, Duvic M, Huen A, Pacheco T, Zwerner JP, Lee ST, Girardi M, Querfeld C, Bohjanen K, Olsen E, Wood GS, Rumage A, Donini O, Haulenbeek A, Schaber CJ, Straube R, Pullion C, Rook AH, Poligone B. Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial. JAMA Dermatol 2022; 158:1031-1039. [PMID: 35857290 PMCID: PMC9301595 DOI: 10.1001/jamadermatol.2022.2749] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). Objectives To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. Design, Settings, and Participants This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. Interventions In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. Main Outcomes and Measures The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020. Results The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred. Conclusion and Relevance The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile. Trial Registration ClinicalTrials.gov Identifier: NCT02448381.
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Affiliation(s)
- Ellen J. Kim
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | | | | | - Henry K. Wong
- University of Arkansas for Medical Sciences, Little Rock
| | | | - Joan Guitart
- Feinberg School of Medicine at Northwestern University, Chicago, Illinois
| | - James Appel
- PMG Research of Wilmington, Wilmington, North Carolina
- Campbell University−Sampson Regional Medical Center, Buies Creek, North Carolina
| | - Larisa Geskin
- Columbia University Medical Center, New York, New York
| | - Edward Lain
- Austin Institute for Clinical Research, Pflugerville, Texas
| | - Neil J. Korman
- University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | | | - Neda Nikbakht
- Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Kenneth Dawes
- Dawes Fretzin Dermatology Group, Indianapolis, Indiana
| | - Oleg Akilov
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Joi Carter
- Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
| | - Michi Shinohara
- University of Washington−Seattle Cancer Care Alliance, Seattle
| | | | | | - Neal Bhatia
- Therapeutics Clinical Research, San Diego, California
| | - Amy Musiek
- Washington University School of Medicine, St Louis, Missouri
| | | | - Youn H. Kim
- Stanford University School of Medicine, Stanford, California
| | - Dirk Elston
- Medical University of South Carolina, Charleston
| | - Erin Boh
- Tulane University, New Orleans, Louisiana
| | | | - Auris Huen
- University of Texas−MD Anderson Cancer Center, Houston
| | | | | | - Seung Tae Lee
- University of Maryland Comprehensive Cancer Center, Baltimore
| | | | | | | | - Elise Olsen
- Duke University Medical Center, Durham, North Carolina
| | | | | | | | | | | | | | | | - Alain H. Rook
- Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Brian Poligone
- Rochester Skin Lymphoma Medical Group, Fairport, New York
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Hawkins N, Muszbek N, Evans R, Dequen-O'Byrne P, Jones T, McNamara L. Adjusting for treatment crossover in the MAVORIC trial: survival in advanced mycosis fungoides and Sézary syndrome. J Comp Eff Res 2022; 11:805-813. [PMID: 35678206 DOI: 10.2217/cer-2022-0070] [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
Background: Relative overall survival (OS) estimates reported in the MAVORIC trial are potentially confounded by a high proportion of patients randomized to vorinostat switching to mogamulizumab; furthermore, vorinostat is not used in clinical practice in the UK. Methods: Three methods were considered for crossover adjustment. Survival post-crossover adjustment was compared with data from the Hospital Episode Statistics (HES) to contextualize estimates. Results: Following adjustment, the OS hazard ratio for mogamulizumab versus vorinostat was 0.42 (95% CI: 0.18, 0.98) using the method considered most appropriate based on an assessment of assumptions and comparison with HES. Conclusions: OS of mogamulizumab relative to vorinostat may be underestimated in MAVORIC due to the presence of crossover. The HES database was used to validate this adjustment.
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Affiliation(s)
| | | | | | | | - Trefor Jones
- Payer Value and Patient Access, Kyowa Kirin, Marlow, SL7 1HZ, UK
| | - Linda McNamara
- Payer Value and Patient Access, Kyowa Kirin, Marlow, SL7 1HZ, UK
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36
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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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37
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Angelov D, Dillon J, Mellerick L, Pender E, Bacon L, Lee G, Higgins L, McCarty H, Gillham C, Quinn J, O'Gorman S, Leonard N, McMenamin M, Vandenberghe E. Allogeneic transplantation in Cutaneous T-cell Lymphoma: improved outcomes associated with early transplantation and acute graft versus host disease. Bone Marrow Transplant 2022; 57:1332-1334. [PMID: 35596064 DOI: 10.1038/s41409-022-01713-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 05/10/2022] [Accepted: 05/12/2022] [Indexed: 11/09/2022]
Affiliation(s)
- Daniel Angelov
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland.
| | - James Dillon
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Lisa Mellerick
- Department of Histopathology, St. James's Hospital, Dublin 8, Ireland
| | - Emily Pender
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Larry Bacon
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Greg Lee
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Liz Higgins
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | | | - Charles Gillham
- Department of Radiation Oncology, St James's Hospital, Dublin 8, Ireland
| | - John Quinn
- Department of Haematology, Beaumont Hospital, Dublin 9, Ireland
| | - Susan O'Gorman
- Department of Dermatology, St. James's Hospital, Dublin 8, Ireland
| | - Niamh Leonard
- Department of Histopathology, St. James's Hospital, Dublin 8, Ireland
| | - Máirín McMenamin
- Department of Histopathology, St. James's Hospital, Dublin 8, Ireland
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38
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Braunstein Z, McLaughlin E, Ruiz M, Wei L, Bumma N, Benson D, Devarakonda S, Chaudhry M, Khan A, Cottini F, Hanel W, Baiocchi R, Chung C, Addison D, Couette N, Meara A, Jarjour W, Porcu P, Mishra A, Reneau JC, Rosko AE, Brammer JE. Incidence, Treatment, and Survival of Patients With T-Cell Lymphoma, T-Cell Large Granular Leukemia, and Concomitant Plasma Cell Dyscrasias. Front Oncol 2022; 12:858426. [PMID: 35574379 PMCID: PMC9106372 DOI: 10.3389/fonc.2022.858426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/07/2022] [Indexed: 11/13/2022] Open
Abstract
T-Cell malignancies are a group of heterogeneous disorders composed of primary cutaneous T-cell lymphomas (CTCLs), peripheral T-cell lymphomas (PTCLs), and T-cell leukemias, including T-cell large granular lymphocytic leukemia (T-LGLL). Cases of patients with combined T-cell malignancies and plasma cell dyscrasias (PCD) are reported in the literature, but these are mostly limited to case reports or small case series with <10 patients. Here, we described the clinical course of 26 patients and report baseline characteristics and clinical outcomes including overall survival (OS), progression-free survival (PFS), and objective response rates (ORRs) in this unique population. There was no survival difference in patients with CTCL or T-LGLL and concomitant PCD when treated with standard therapy directed at the T-cell malignancy when compared to historical controls. However, patients with PTCL and concomitant PCD had significantly inferior outcomes with rapid progression and worse OS and PFS at 1.7 years (p=0.006) and 4.8 months (p=0.08), respectively, when compared to historical controls for patients with PTCL, although the limited number of patients included in this analysis precludes drawing definitive conclusions. Treatment directed at the T-cell malignancy resulted in the eradication of the PCD clone in multiple patients (15.4%) including one with multiple myeloma (MM) who experienced a complete response after starting therapy directed at the T-cell malignancy. For patients with T-cell malignancies and concomitant PCD, treatment with standard T-cell-directed therapies is recommended based on this analysis with continued follow-up and monitoring of the concomitant PCD. Further studies are needed to definitively elucidate the increased risk of relapse in patients with PTCL and concomitant PCD, and larger, multi-center cohorts are needed to validate these findings across T-cell malignancies and PCDs.
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Affiliation(s)
- Zachary Braunstein
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Eric McLaughlin
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
| | - Miguel Ruiz
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Lai Wei
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
| | - Naresh Bumma
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Don Benson
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Srinivas Devarakonda
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Maria Chaudhry
- Division of Hematology, George Washington Cancer Center, George Washington University, Washington, DC, United States
| | - Abdullah Khan
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Francesca Cottini
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Walter Hanel
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Robert Baiocchi
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Catherine Chung
- Department of Dermatology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Daniel Addison
- Cardio-Oncology Program, Division of Cardiology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Nina Couette
- Division of Rheumatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Alexa Meara
- Division of Rheumatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Wael Jarjour
- Division of Rheumatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Pierluigi Porcu
- Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology and Department of Cancer Biology, Sydney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
| | - Anjali Mishra
- Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology, Sydney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
| | - John C. Reneau
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Ashley E. Rosko
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Jonathan E. Brammer
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
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Banciu ML, Dobrica EC, Soare C, Malciu AM, Voiculescu VM. Healthcare Disparities in the Management of Indolent Mycosis Fungoides. Cureus 2022; 14:e24098. [PMID: 35573524 PMCID: PMC9106548 DOI: 10.7759/cureus.24098] [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: 04/13/2022] [Indexed: 11/18/2022] Open
Abstract
Mycosis fungoides represents the most common cutaneous T-cell lymphoma, clinically manifested with evolving skin lesions, including patches, plaques, tumors, and erythroderma. Early diagnosis remains difficult to establish because it mimics several benign skin conditions, but maintaining a high index of suspicion for the disease is essential in preventing the progression of a potentially fatal disease. We report the case of a 69-year-old female who presented in our dermatology clinic in 2018 with scaly, indurated, itchy erythematous-violaceus patches and plaques, and tumors disseminated throughout the skin evolving for nine years. Skin biopsy supplemented with immunohistochemical staining established the diagnosis of mycosis fungoides. Due to the equivocal clinical presentation and the lack of extracutaneous manifestations, the patient received conventional therapy according to the stage of the disease. The rapidly progressive evolution of the cutaneous lesions in the last year of the disease determined the patient’s death despite instituting systemic chemotherapy. Patient follow-up and a multidisciplinary approach are essential to diagnose and manage this disease in its early stages. This will prevent the progression to a life-threatening malignancy and the use of immunosuppressive therapy, which can cause serious side effects.
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40
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Mitteldorf C, Kampa F, Ströbel P, Schön MP, Kempf W. Intraindividual variability of
CD30
expression in mycosis fungoides –implications for diagnostic evaluation and therapy. Histopathology 2022; 81:55-64. [DOI: 10.1111/his.14660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 03/24/2022] [Accepted: 04/04/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Christina Mitteldorf
- Department of Dermatology, Venereology and Allergology University Medical Center Göttingen Germany
| | - Franziska Kampa
- Department of Dermatology, Venereology and Allergology University Medical Center Göttingen Germany
| | | | - Michael P. Schön
- Department of Dermatology, Venereology and Allergology University Medical Center Göttingen Germany
- Lower Saxony Institute of Occupational Dermatology
| | - Werner Kempf
- Kempf und Pfaltz Histologische Diagnostik, Affolternstrasse 56, CH‐8050 Zürich Switzerland
- Department of Dermatology University Hospital Zurich CH‐8091 Zurich Switzerland
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41
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Franceschi J, Ehret M, Visseaux L, Durlach A, Barbe C, Durot É, Grange F. Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas. Acta Derm Venereol 2022; 102:adv00676. [PMID: 35083494 PMCID: PMC9558323 DOI: 10.2340/actadv.v102.1087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16–101 months.
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Affiliation(s)
- Joséphine Franceschi
- Department of Dermatology, Reims University Hospital, rue du Général Koenig, FR-51100 Reims, France.
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Vermeer MH, Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S. Flow cytometry for the assessment of blood tumour burden in cutaneous T-cell lymphoma: towards a standardised approach. Br J Dermatol 2022; 187:21-28. [PMID: 35157307 PMCID: PMC9541328 DOI: 10.1111/bjd.21053] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/28/2022] [Accepted: 02/09/2022] [Indexed: 11/30/2022]
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are the best-studied subtypes of cutaneous T-cell lymphoma, a rare non-Hodgkin lymphoma that primarily presents in the skin but can also involve blood, lymph nodes, and viscera. The role of blood involvement in the assessment and staging of MF and SS has evolved in recent years from being classed as simply 'present' or 'absent', with no impact on staging, to full analysis of abnormal peripheral-blood T cells using flow cytometry (FC) to detect and quantify aberrant T-cell phenotypes and polymerase chain reaction (PCR) to characterise T-cell receptor gene rearrangements. These sensitive peripheral-blood assessments are replacing manual Sézary cell counts and have become an important part of clinical work-up in MF and SS, providing the potential for more accurate prognostication and appropriate management. However, although international recommendations now include guidelines for FC analysis of peripheral-blood markers for staging purposes, many clinics only perform these analyses in advanced-stage patients, if at all, and there is still a need for standardised use of validated markers. Standardisation of a single effective multiparameter FC panel would allow for accurate identification and quantification of blood tumour burden for diagnosis, staging, assessment of therapeutic response, and monitoring of disease progression at all stages of disease. Once defined, validation of an MF/SS biomarker FC panel will enable uptake into clinical settings along with associated standardisation of protocols and reagents. This review discusses the evolution of the role of FC in evaluating blood involvement in MF and SS, considers recently published international guidelines, and identifies evidence gaps for future research that will allow for standardisation of FC in MF and SS.
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Affiliation(s)
- Maarten H Vermeer
- Dermatology Department, Leiden University Medical Center, Leiden, the Netherlands
| | - Helene Moins-Teisserenc
- Université de Paris, Institut de Recherche Saint Louis, INSERM UMR1160, Paris, France.,Hematology Laboratory, AP-, HP, Hôpital Saint Louis, Paris, France
| | - Martine Bagot
- Université de Paris, Institut de Recherche Saint Louis, INSERM UMRS976, Onco-Dermatology and Therapies, Paris, France.,Département de Dermatologie, AP-, HP, Hôpital Saint Louis, Paris, France
| | - Pietro Quaglino
- Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Turin, Italy
| | - Sean Whittaker
- St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London, SE1 9RT, UK
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Reiter O, Amitay-Laish I, Oren-Shabtai M, Feinmesser M, Amitai DB, Hodak E. Pediatric mycosis fungoides - characteristics, management, and outcomes with particular focus on the folliculotropic variant. J Eur Acad Dermatol Venereol 2022; 36:671-679. [PMID: 35080278 DOI: 10.1111/jdv.17971] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 11/22/2021] [Accepted: 12/07/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The literature on pediatric mycosis fungoides (MF) and especially its folliculotropic variant (FMF) is sparse. OBJECTIVES To describe the clinical manifestations, treatments, outcomes and long-term course of pediatric MF, including FMF. METHODS A retrospective analysis was conducted of all consecutive MF patients diagnosed at ≤18 years attending two medical centers in 1995-2015. RESULTS The cohort included 71 patients, all but 2 of whom had early-stage disease: hypopigmented (55%) folliculotropic (42%) and classical MF (39%), alone or in combination. The head and neck area was involved in 43% of patients with early-stage FMF compared to 12% of the non-FMF group (p=0.004). There was no difference in the involvement of other body areas between the groups. Pruritus, although mild, was more often recorded among patients with early-stage FMF compared to non-FMF (58% vs. 29%, respectively, P=0.02). Complete response (CR) was achieved in 60 of the 69 patients with early-stage MF (87%) after an average of 1.8 treatment modalities. NBUVB was the most administered treatment to non-FMF patients with CR rates of 63% versus 29% of FMF patients (P=0.04). Systemic/bath PUVA, or UVA+NBUVB were the most administered treatments to FMF patients with CR rates of 60% versus 81% for non-FMF patients (P=0.17). During a mean follow-up of 9.2 years (range 1-24), stage progression was observed in 4 (6%) of the patients with early-stage disease, 2 of whom (all FMF) to advanced stage. CONCLUSIONS Pediatric MF presents as an early-stage disease with over-representation of hypopigmented and FMF variants. NBUVB and UVA-based therapies yield good response rates in non-FMF and FMF patients, respectively. Disease course is indolent, and even on relatively long follow-up, it has a very low progression rate from early to advanced-stage disease, occurring in patients with FMF. We propose a treatment algorithm for pediatric MF.
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Affiliation(s)
- O Reiter
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, 4941492, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - I Amitay-Laish
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, 4941492, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - M Oren-Shabtai
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, 4941492, Israel
| | - M Feinmesser
- Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, 4941492, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - D Ben Amitai
- Pediatric Dermatology Unit, Schneider Children's Medical Center of Israel, Petach Tikva, 49420235, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - E Hodak
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, 4941492, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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44
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Zhang Y, Seminario-Vidal L, Varnadoe C, Lu Y, Dong N, Salamanca C, Whiddon S, Bennett J, Hargis R, Liu H, Montejo M, Hussaini M, Harro C, Messina J, Benson K, Pinilla-Ibarz J, Conejo-Garcia J, Sokol L. Clinical characteristics and prognostic factors of 70 patients with Sézary syndrome: a single-institutional experience at Moffitt cancer center. Leuk Lymphoma 2022; 63:109-116. [PMID: 34467825 PMCID: PMC9167451 DOI: 10.1080/10428194.2021.1971218] [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: 01/03/2023]
Abstract
Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma, with a median overall survival (OS) rate of 2-4 years. Few studies have described the clinical outcome of SS patients since 2012. We retrospectively analyzed 70 patients diagnosed with SS treated at a high-volume tertiary cancer center between 2000 and 2018. Overall survival at 1 and 5 years was 84.1% and 50.7%, respectively. Univariate analyses identified older age (>65 years) and male sex as poor prognostic factors. Five patients presented with circulating large granular lymphocytic proliferation and had a favorable prognosis. Targeted therapies were effective in treating refractory/relapsed SS patients with a durable response. Therapeutic advancements and the comprehensive treatments used in a multidisciplinary clinic improved OS rates.
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Affiliation(s)
- Yumeng Zhang
- Department of Medicine, University of South Florida& H. Lee Moffitt Cancer Center and Research Institute, FL, USA, USA
| | - Lucia Seminario-Vidal
- Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | | | - Yuanyuan Lu
- College of Public Health, University of South Florida, Tampa, FL, USA
| | - Ning Dong
- Department of Medicine, University of South Florida& H. Lee Moffitt Cancer Center and Research Institute, FL, USA, USA
| | - Christopher Salamanca
- Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Shannen Whiddon
- Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Janice Bennett
- Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Rebecca Hargis
- Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Hien Liu
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Michael Montejo
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Mohammad Hussaini
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Carly Harro
- Department of Cancer Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Jane Messina
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Kaaron Benson
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Javier Pinilla-Ibarz
- Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Jose Conejo-Garcia
- Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Lubomir Sokol
- Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
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45
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Kołkowski K, Trzeciak M, Sokołowska-Wojdyło M. Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas. Int J Mol Sci 2021; 22:13388. [PMID: 34948183 PMCID: PMC8703592 DOI: 10.3390/ijms222413388] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/05/2021] [Accepted: 12/06/2021] [Indexed: 12/24/2022] Open
Abstract
The impact of new and emerging therapies on the microenvironment of primary cutaneous lymphomas (PCLs) has been recently raised in the literature. Concomitantly, novel treatments are already used or registered (dupilumab, upadacitinib) and others seem to be added to the armamentarium against atopic dermatitis. Our aim was to review the literature on interleukins 4, 13, 22, and 31, and JAK/STAT pathways in PCLs to elucidate the safety of using biologics (dupilumab, tralokinumab, fezakinumab, nemolizumab) and small molecule inhibitors (upadacitinib, baricitinib, abrocitinib, ruxolitinib, tofacitinib) in the treatment of atopic dermatitis. We summarized the current state of knowledge on this topic based on the search of the PubMed database and related references published before 21 October 2021. Our analysis suggests that some of the mentioned agents (dupilumab, ruxolitinib) and others may have a direct impact on the progression of cutaneous lymphomas. This issue requires further study and meticulous monitoring of patients receiving these drugs to ensure their safety, especially in light of the FDA warning on tofacitinib. In conclusion, in the case of the rapid progression of atopic dermatitis/eczema, especially in patients older than 40 years old, there is a necessity to perform a biopsy followed by a very careful pathological examination.
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Affiliation(s)
- Karol Kołkowski
- Dermatological Students Scientific Association, Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland
| | - Magdalena Trzeciak
- Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (M.T.); (M.S.-W.)
| | - Małgorzata Sokołowska-Wojdyło
- Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (M.T.); (M.S.-W.)
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Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. Blood Adv 2021; 6:2290-2302. [PMID: 34872108 PMCID: PMC9006301 DOI: 10.1182/bloodadvances.2021005714] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 11/14/2021] [Indexed: 11/24/2022] Open
Abstract
CD70 is highly expressed in mature TCL, especially in CTCL, and an ideal therapeutic target for ADC. SGN-CD70A, a novel ADC, induces complete eradication of established tumors assessed by cell-free DNA and prolongs survival in CTCL PDXs. CD70 is a member of the tumor necrosis factor receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T-cell lymphomas and conducted preclinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate (ADC), using patient-derived xenograft cutaneous T-cell lymphoma (CTCL PDX) models. CD70 expression was examined by immunohistochemical (IHC) stains in 49 diagnostic specimens of T-cell lymphomas. The activities of SGN-CD70A in growth inhibition and apoptosis induction were examined in CTCL cell lines and primary CTCL tumor cells. Using previously established CTCL PDXs, we conducted a dose-finding trial followed by a phase 2-like trial to evaluate the optimal dosing and the efficacy of SGN-CD70A in tumor-bearing PDX animals. The therapeutic efficacy of SGN-CD70A was measured by tumor-associated cell-free DNA (cfDNA) and survival of treated PDXs. We found that CD70 is highly expressed in T-cell lymphomas, especially in CTCL. SGN-CD70A inhibited cell growth and induced apoptosis in CD70-expressing CTCL cell lines and primary tumors cells. Additionally, SGN-CD70A at 100 μg/kg and 300 μg/kg prolonged the survival of PDXs in a dose-dependent manner. Finally, treatment with 3 doses of SGN-CD70A at 300 μg/kg was superior to a single-dose treatment in survival prolongation (median survival: 111 days vs 39 days; P = .017). Most importantly, multiple dosing of SGN-CD70A induced complete eradication of established tumors in PDXs measured by cfDNA. Our results demonstrated marked antitumor activity of SGN-CD70A in CTCL PDXs, providing compelling support for its clinical investigation.
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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: 10] [Impact Index Per Article: 2.5] [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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Xiao MZX, Hennessey D, Iyer A, O'Keefe S, Zhang F, Sivanand A, Gniadecki R. Transcriptomic Changes During Stage Progression of Mycosis Fungoides. Br J Dermatol 2021; 186:520-531. [PMID: 34528236 DOI: 10.1111/bjd.20760] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of MF patients develop skin tumors, a hallmark of progression to the advanced stage and is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. METHODS We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n=12) as well as plaques and tumors from patients in late-stage disease (late-stage plaques [LSP], n=10, and tumors [TMR], n=15). Gene Ontology (GO) and KEGG analysis were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumors. RESULTS The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), Th2/Th9 signaling (IL4, STAT3, STAT5, STAT6), meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via hematogenous self-seeding. CONCLUSION Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions may be caused by hematogenous cell percolation between discrete skin lesions.
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Affiliation(s)
- M Z X Xiao
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - D Hennessey
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - A Iyer
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - S O'Keefe
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - F Zhang
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - A Sivanand
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - R Gniadecki
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
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Roccuzzo G, Giordano S, Fava P, Pileri A, Guglielmo A, Tonella L, Sanlorenzo M, Ribero S, Fierro MT, Quaglino P. Immune Check Point Inhibitors in Primary Cutaneous T-Cell Lymphomas: Biologic Rationale, Clinical Results and Future Perspectives. Front Oncol 2021; 11:733770. [PMID: 34485162 PMCID: PMC8415544 DOI: 10.3389/fonc.2021.733770] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/30/2021] [Indexed: 12/14/2022] Open
Abstract
Primary cutaneous T-cell lymphomas (PCTCL) are the most common types of cutaneous lymphomas, with Mycosis fungoides as the most frequent subtype. Besides early stages which usually have a good prognosis, advanced stages remain a great therapeutic challenge with low survival rates. To date, none of the currently available therapeutic options have significantly improved the outcomes of advanced cutaneous lymphomas. Recent studies have demonstrated that immune-checkpoint molecules, such as PD-1 and CTLA-4, play part in the proliferation pathways of neoplastic T-cells, as well as in other tumors. Hence, the potential role of immune-checkpoint-inhibitors in treating cutaneous lymphomas has been investigated in the last years. Herein, we outline the current knowledge regarding the role of immune-checkpoint molecules in PCTCL, their signaling pathways, microenvironment and therapeutic inhibition rationale. Moreover, we review the published data on immunotherapies in PCTCL and summarize the currently ongoing clinical trials in this field.
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Affiliation(s)
- Gabriele Roccuzzo
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Silvia Giordano
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Paolo Fava
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Alessandro Pileri
- Dermatology-IRCCS Policlinico di Sant'Orsola Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Dermatology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Alba Guglielmo
- Dermatology-IRCCS Policlinico di Sant'Orsola Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Dermatology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Luca Tonella
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Martina Sanlorenzo
- Department of Medicine, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Simone Ribero
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Maria Teresa Fierro
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Pietro Quaglino
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
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50
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Jung JM, Lim DJ, Won CH, Chang SE, Lee MW, Lee WJ. Mycosis Fungoides in Children and Adolescents: A Systematic Review. JAMA Dermatol 2021; 157:431-438. [PMID: 33656521 DOI: 10.1001/jamadermatol.2021.0083] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Importance Comprehensive data on childhood mycosis fungoides (MF) is scarce. Objective To describe clinical features, immunophenotypes, various treatment options, and prognosis of MF in children and adolescents. Evidence Review This systematic review searched MEDLINE via PubMed, Embase, Cochrane, and Scopus databases in October 2019. The search terms included mycosis fungoides, infant, children, and adolescent. No filter for the publication period was used, but studies written in a language other than English were excluded. Reference lists of the relevant articles were also searched manually. Case series and case reports were included if data on childhood MF were extractable. The Asan Medical Center database for cases of childhood MF was also searched. Patients were treated from January 1, 1990, to July 31, 2019, and were younger than 20 years at the time of diagnosis. The methodologic quality of the included studies was assessed with items from the Newcastle-Ottawa scale. Data were analyzed from December 9, 2019, to September 4, 2020. Findings A total of 571 unique patients were included. The mean (SD) age at diagnosis was 12.2 (4.2) years; at onset, 8.6 (4.2) years. The female-to-male ratio was 1:1.6 (350 male patients [61.3%]). Among 522 patients with data available at diagnosis, stage 1 disease constituted 478 cases (91.6%), followed by stage 2 (39 [7.5%]) and stage 4 (5 [1.0%]). Among the 567 patients with data available, the most common variant of MF was the hypopigmented form (309 [54.5%]), followed by classic MF (187 [33.0%]). The MF lesions were predominantly the CD4+ and CD8+ immunophenotype in 99 (49.5%) and 79 (39.5%) of 200 patients, respectively. Among the treatments, narrowband UV-B was the most frequently used (150 of 426 [35.2%]). Most patients were alive with the disease (185 of 279 [66.3%]); 83 of 279 (29.8%) were in complete remission; and 11 of 279 (3.9%) had died by the last follow-up. A longer time from onset to diagnosis (hazard ratio [HR], 1.24; 95% CI, 1.06-1.45), granulomatous slack skin (HR, 12.25; 95% CI, 1.99-75.26), granulomatous MF (HR, 14.59; 95% CI, 1.31-162.00), a history of organ transplant (HR, 10.15; 95% CI, 0.98-105.37), and stage 2 disease at the time of diagnosis (HR, 10.22; 95% CI, 2.94-35.50) were associated with worse outcomes. Conclusions and Relevance The findings of this review suggest that there is often a significant delay until the establishment of a correct diagnosis of childhood MF, which may be detrimental to the prognosis.
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Affiliation(s)
- Joon Min Jung
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dong Jun Lim
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chong Hyun Won
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung Eun Chang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Mi Woo Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Woo Jin Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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