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Youn H Kim - One of the best experts on this subject based on the ideXlab platform.
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lymph node involvement by mycosis fungoides and Sezary Syndrome mimicking angioimmunoblastic t cell lymphoma
Human Pathology, 2015Co-Authors: Robert E Leblanc, Youn H Kim, Martina I Lefterova, Carlos Suarez, Mahkam Tavallaee, Iris Schrijver, Jinah Kim, Dita GratzingerAbstract:Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sezary Syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sezary Syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.
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prognostic factors prognostic indices and staging in mycosis fungoides and Sezary Syndrome where are we now
British Journal of Dermatology, 2014Co-Authors: Julia Scarisbrick, Sean Whittaker, Gary S Wood, Maarten H Vermeer, Youn H Kim, H M Prince, Pietro QuaglinoAbstract:Summary Mycosis fungoides is the most prevalent form of primary cutaneous T-cell lymphoma. Patients frequently present with early-stage disease typically associated with a favourable prognosis and survival of 10–35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sezary Syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA–IIA (early-stage disease) and IIB–IVB (advanced-stage disease) and provides prognostic information, but some patients with tumour-stage disease (IIB) have a worse prognosis than those with erythrodermic-stage (III). Conversely, patients with plaque-stage (IB) folliculotropic mycosis fungoides may have a worse outcome than those with tumour-stage (IIB). The more recent staging system of the European Organisation for the Research and Treatment of Cancer/International Society for Cutaneous Lymphoma has been designed to reflect tumour burden at different sites. However, this staging system has not been validated prospectively for prognosis. Furthermore, this staging system does not include a detailed measurement of skin tumour burden, as indicated by the modified skin weighted severity assessment tool. This assessment measures body surface area of disease and is weighted to record patch, plaque and tumour to produce a numerical value from 0·5 to 400 and is an established endpoint for clinical studies. Nor does this staging include clinicopathological features associated with a poor prognosis such as folliculotropism. Here we review the clinical, haematological, pathological and genotypic parameters outside the staging system, which may affect survival in mycosis fungoides and Sezary Syndrome. Most studies are retrospective and single centre. The identification of poor prognostic factors may be used to develop a prognostic index to use alongside staging, which may be of benefit in mycosis fungoides/Sezary Syndrome to identify patients with a potentially poor prognosis.
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a meta analysis of patients receiving allogeneic or autologous hematopoietic stem cell transplant in mycosis fungoides and Sezary Syndrome
Biology of Blood and Marrow Transplantation, 2009Co-Authors: Youn H Kim, Richard T Hoppe, Phillip W Lavori, Keith StockerlgoldsteinAbstract:Abstract The survival outlook in advanced mycosis fungoides (MF) is poor. Autologous and allogeneic stem cell transplants (SCT) have been shown, in small case series and case reports, to have the potential for long-term remission or to alter disease course. Allogeneic SCT is thought to have a curative potential secondary to a graft-versus-lymphoma (GVL) effect. A patient-level meta-analysis was performed to compare the outcome of allogeneic versus autologous SCT in patients with MF/Sezary Syndrome (SS) using 39 cases from the literature. There were a total of 20 allogeneic and 19 autologous transplant cases. The gender, age, and stage distribution was similar between the transplant groups. The allogeneic group received significantly more systemic therapies prior to transplant (P
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review of the treatment of mycosis fungoides and Sezary Syndrome a stage based approach
Journal of The National Comprehensive Cancer Network, 2008Co-Authors: Steven M Horwitz, Madeleine Duvic, Elise A Olsen, Pierliugi Porcu, Youn H KimAbstract:The NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin's Disease were recently revised to include recommendations for treating mycosis fungoides and Sezary Syndrome. These uncommon lymphomas require a specialized evaluation and use a unique TNMB staging system. Unlike the other forms of non-Hodgkin's lymphomas, stage overwhelmingly determines prognosis and defines radically different treatment approaches. For patients with early-stage disease, initial treatment with skin-directed therapies is preferred, and many patients never require systemic therapy. For patients with refractory or advanced-stage disease, biologic therapies are often the first choices, whereas chemotherapies are reserved for later in the disease course. Many milder therapies may be repeated several times in the disease course, and maintenance and tapering strategies are common. This article also discusses the emerging role of allogeneic stem cell transplantation.
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second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary Syndrome evidence from population based and clinical cohorts
Archives of Dermatology, 2007Co-Authors: Kathie P Huang, Richard T Hoppe, Martin A Weinstock, Christina A Clarke, Alex Mcmillan, Youn H KimAbstract:Objective To assess risks for developing second malignancies in patients with mycosis fungoides or Sezary Syndrome. Design Retrospective study of 2 cohorts. Setting Nine population-based US cancer registries that constitute the Surveillance, Epidemiology, and End Results Program (SEER-9), and Stanford University referral center cohort of patients with cutaneous lymphoma. Patients Patients with mycosis fungoides or Sezary Syndrome from the SEER-9 registry diagnosed and followed up from 1984 through 2001 and from the Stanford University cohort diagnosed and followed up from 1973 through 2001. Main Outcome Measures Relative risk was estimated using the standardized incidence ratio (SIR). The expected cancer incidence for both cohorts was calculated using age-, sex-, race-, and calendar year–specific SEER-9 incidence rates for the general population. Nonmelanoma skin cancers were excluded because these cancers are not routinely reported by the SEER database. Results In the SEER-9 cohort (n = 1798), there were 197 second instances of cancer (SIR = 1.32; 95% confidence interval [CI], 1.15-1.52) at all sites. Significantly elevated risk ( P P P P Conclusion Updated SEER (population based) and Stanford (clinic based) data confirm the generalizability of earlier findings of increased risk of lymphoma in patients with mycosis fungoides or Sezary Syndrome.
Christiane Querfeld - One of the best experts on this subject based on the ideXlab platform.
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leukaemic variants of cutaneous t cell lymphoma erythrodermic mycosis fungoides and Sezary Syndrome
Best Practice & Research Clinical Haematology, 2019Co-Authors: X Martinez, Christiane Querfeld, Jasmine Zain, Steven T Rosen, Farah Abdulla, Cosimo Di RaimondoAbstract:Abstract Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients’ ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.
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primary cutaneous t cell lymphomas mycosis fungoides and Sezary Syndrome
Cancer treatment and research, 2019Co-Authors: Christiane Querfeld, Jasmine Zain, Steven T RosenAbstract:Mycosis fungoides and Sezary Syndrome are the most common subtypes of all primary cutaneous lymphomas and represent complex diseases that require a multidisciplinary assessment by dermatologists, oncologists, and pathologists. Staging and work-up are critical to guarantee an optimal treatment plan that includes skin-directed and/or systemic regimens depending on the clinical stage, tumor burden, drug-related side effect profile, and patient comorbidities. However, there is no cure and patients frequently relapse, requiring repeated treatment courses for disease control. The study of the tumor microenvironment and molecular mechanisms of these rare neoplasms may assist in the development of new immune therapies providing promising treatment approaches tailored for patients with relapse/refractory disease.
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integrating novel systemic therapies for the treatment of mycosis fungoides and Sezary Syndrome
Best Practice & Research Clinical Haematology, 2018Co-Authors: Miles H Prince, Christiane QuerfeldAbstract:Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies. In general, systemic chemotherapy should be reserved for patients who fail to respond to biological agents. Such biological agents include interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective for patients with Sezary Syndrome. Allogeneic transplantation is becoming increasing used for younger patients. Novel agents in advanced development include the monoclonal antibody IPH4102,duvelisib,and the new modified formulation of denileukin diftitox. The choice of agents for patients is typically a balance of patient factors (age, co-morbidities, geographic location), relative efficacy and toxicity.
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hematopoietic stem cell transplant for mycosis fungoides and Sezary Syndrome
Dermatologic Clinics, 2015Co-Authors: Pooja Virmani, Christiane Querfeld, Jasmine Zain, Steven T Rosen, Patricia L MyskowskiAbstract:Mycosis fungoides (MF) and Sezary Syndrome (SS) are common types of primary cutaneous T-cell lymphoma. Early-stage MF has a favorable prognosis and responds well to skin-directed regimens. Patients with advanced-stage MF, transformed MF, and SS are treated with combined systemic and skin-directed therapies. However, the disease is incurable with standard regimens, and frequent relapses are common. Owing to the lack of improvement in overall survival with standard regimens, hematopoietic stem cell transplant (HSCT) has been explored as a potential curative option. This article reviews the role of HSCT in MF/SS and discusses data regarding conditioning regimens, treatment-related complications, and outcomes.
Richard T Hoppe - One of the best experts on this subject based on the ideXlab platform.
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how i treat mycosis fungoides and Sezary Syndrome
Blood, 2009Co-Authors: Miles H Prince, Sean Whittaker, Richard T HoppeAbstract:Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sezary Syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional "stage-based" approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies.
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a meta analysis of patients receiving allogeneic or autologous hematopoietic stem cell transplant in mycosis fungoides and Sezary Syndrome
Biology of Blood and Marrow Transplantation, 2009Co-Authors: Youn H Kim, Richard T Hoppe, Phillip W Lavori, Keith StockerlgoldsteinAbstract:Abstract The survival outlook in advanced mycosis fungoides (MF) is poor. Autologous and allogeneic stem cell transplants (SCT) have been shown, in small case series and case reports, to have the potential for long-term remission or to alter disease course. Allogeneic SCT is thought to have a curative potential secondary to a graft-versus-lymphoma (GVL) effect. A patient-level meta-analysis was performed to compare the outcome of allogeneic versus autologous SCT in patients with MF/Sezary Syndrome (SS) using 39 cases from the literature. There were a total of 20 allogeneic and 19 autologous transplant cases. The gender, age, and stage distribution was similar between the transplant groups. The allogeneic group received significantly more systemic therapies prior to transplant (P
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second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary Syndrome evidence from population based and clinical cohorts
Archives of Dermatology, 2007Co-Authors: Kathie P Huang, Richard T Hoppe, Martin A Weinstock, Christina A Clarke, Alex Mcmillan, Youn H KimAbstract:Objective To assess risks for developing second malignancies in patients with mycosis fungoides or Sezary Syndrome. Design Retrospective study of 2 cohorts. Setting Nine population-based US cancer registries that constitute the Surveillance, Epidemiology, and End Results Program (SEER-9), and Stanford University referral center cohort of patients with cutaneous lymphoma. Patients Patients with mycosis fungoides or Sezary Syndrome from the SEER-9 registry diagnosed and followed up from 1984 through 2001 and from the Stanford University cohort diagnosed and followed up from 1973 through 2001. Main Outcome Measures Relative risk was estimated using the standardized incidence ratio (SIR). The expected cancer incidence for both cohorts was calculated using age-, sex-, race-, and calendar year–specific SEER-9 incidence rates for the general population. Nonmelanoma skin cancers were excluded because these cancers are not routinely reported by the SEER database. Results In the SEER-9 cohort (n = 1798), there were 197 second instances of cancer (SIR = 1.32; 95% confidence interval [CI], 1.15-1.52) at all sites. Significantly elevated risk ( P P P P Conclusion Updated SEER (population based) and Stanford (clinic based) data confirm the generalizability of earlier findings of increased risk of lymphoma in patients with mycosis fungoides or Sezary Syndrome.
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mycosis fungoides and the Sezary Syndrome
Seminars in Oncology, 1999Co-Authors: Youn H Kim, Richard T HoppeAbstract:Mycosis fungoides (MF) and the Sezary Syndrome are a group of extranodal non-Hodgkin's lymphomas of T-cell origin with primary cutaneous involvement. The group distinguishes itself from other primary cutaneous T-cell lymphomas (CTCLs) by its unique clinical features and histopathology. In its early stages, it often resembles common benign dermatoses, and therefore, a definitive diagnosis can be delayed. The affected T cells are characterized by a predominant CD4+ phenotype with frequent loss of CD7 (pan-T-cell antigen) and often demonstrate T-cell receptor (TCR) rearrangement. The prognosis of patients with MF is highly dependent on the extent and type of skin involvement. The initial cutaneous presentation of MF can be patches, plaques, tumors, or erythroderma. Patients who present with limited patch/plaque disease have an outstanding prognosis with an overall long-term survival that is similar to the expected survival of a matched control population. It is exceedingly rare for patients who present with limited or generalized patch/plaque disease without peripheral lymphadenopathy to have extracutaneous involvement. Therefore, the staging evaluation differs for patients with MF versus patients with other non-Hodgkin's lymphomas and should be tailored to the clinical presentation. Patients who have tumorous or erythrodermic skin involvement have a less favorable prognosis, and patients who present with extracutaneous disease have a poor prognosis. There are multiple therapeutic options for patients with MF and the Sezary Syndrome. Selection of a specific treatment plan is based primarily on the clinical stage of the disease. The primary therapy for patients with patch/plaque disease without extracutaneous involvement is a topical regimen, whereas chemotherapy or other aggressive systemic regimens are reserved for those with recalcitrant disease or extracutaneous involvement. There is no evidence that early aggressive systemic therapy is preferable to conservative therapy in the management of limited disease. There are newer combination topical and/or systemic regimens that result in an improved clinical response and possibly a prolonged response duration. For advanced disease, standard therapies are often palliative and successful clinical response is often very short-lived. Therefore, all patients with recalcitrant or extracutaneous disease should be considered for newer investigative therapies.
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prognostic factors in erythrodermic mycosis fungoides and the Sezary Syndrome
Archives of Dermatology, 1995Co-Authors: Youn H Kim, Kay Bishop, Anna Varghese, Richard T HoppeAbstract:Background and Design: There are no large studies evaluating patients with erythrodermic mycosis fungoides and Sezary Syndrome to determine the important prognostic factors that may influence survival. This is important since new treatment modalities have been proposed as superior to existing primary therapies. We performed a retrospective cohort study of 106 patients with erythrodermic mycosis fungoides and Sezary Syndrome, followed up in the Stanford (Calif) Mycosis Fungoides Clinic, to define the important prognostic factors in this group. Results: Patients younger than 65 years have a more favorable survival profile than those 65 years or older ( P P =.055). Lymph node stage is significantly correlated with survival; patients with overall stage III disease have more favorable prognosis than those with stage IV disease ( P P P Conclusions: In patients with erythrodermic mycosis fungoides and Sezary Syndrome, the important prognostic factors are patient age at presentation, the overall stage, and peripheral blood involvement. Survival varies widely, depending on these variables. These prognostic factors should be evaluated when analyzing survival and/or treatment efficacy data of these patients. (Arch Dermatol. 1995;131:1003-1008)
Alain H Rook - One of the best experts on this subject based on the ideXlab platform.
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mogamulizumab in the treatment of advanced mycosis fungoides and Sezary Syndrome safety and efficacy
Expert Review of Anticancer Therapy, 2020Co-Authors: Daniel J Lewis, Alain H RookAbstract:Introduction: Advanced mycosis fungoides (MF) and Sezary Syndrome (SS) are forms of cutaneous T-cell lymphoma characterized by a poor prognosis. Treatments are associated with high rates of relapse...
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mogamulizumab in the treatment of advanced mycosis fungoides and Sezary Syndrome safety and efficacy
Expert Review of Anticancer Therapy, 2020Co-Authors: Daniel J Lewis, Alain H RookAbstract:Advanced mycosis fungoides (MF) and Sezary Syndrome (SS) are forms of cutaneous T-cell lymphoma characterized by a poor prognosis. Treatments are associated with high rates of relapse, and thus the...
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pembrolizumab in relapsed and refractory mycosis fungoides and Sezary Syndrome a multicenter phase ii study
Journal of Clinical Oncology, 2020Co-Authors: Michael S Khodadoust, Alain H Rook, Francine M Foss, Andrei R Shustov, Pierluigi Porcu, Alison J Moskowitz, Satish Shanbhag, Lubomir Sokol, Steven P Fling, Nirasha RamchurrenAbstract:PURPOSETo assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sezary Syndrome (SS).PATIENTS AND METHODSCITN-10 is a single-arm, multicent...
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bexarotene blunts malignant t cell chemotaxis in Sezary Syndrome reduction of chemokine receptor 4 positive lymphocytes and decreased chemotaxis to thymus and activation regulated chemokine
American Journal of Hematology, 2007Co-Authors: Stephen K Richardson, Jeanne B Budgin, Sarah Newton, Maria Wysocka, Bernice M Benoit, Tami L Bach, Julie H Lin, Jessica S Yoon, Charles S Abrams, Alain H RookAbstract:The malignant cells in Sezary Syndrome express the skin trafficking molecules' cutaneous lymphocyte associated antigen (CLA) and chemokine receptor 4 (CCR4). High levels of the CCR4 ligand, thymus, and activation-regulated chemokine (TARC), have been reported in the blood and skin of patients. The rexinoid X-receptor specific retinoid, bexarotene, has contributed to the resolution of cutaneous disease among patients. To evaluate the effects of bexarotene on skin trafficking molecule expression and chemotaxis, peripheral blood mononuclear cells from Sezary Syndrome patients and healthy controls were treated with bexarotene in vitro. CCR4 and CLA expression levels and chemotaxis in response to TARC (6.25 ng/ml) were evaluated among lymphocytes before and after treament with bexarotene (10 μM). Flow cytometric analysis was performed to evaluate CD4, CD26, CLA, and CCR4 cell surface expression. Transwell migration assays were performed to evaluate chemotaxis to TARC. Prior to treatment, malignant cells exhibited higher CCR4 expression (45–90%) and greater than four times more chemotaxis to TARC compared with healthy controls. After treatment with bexarotene for 36–96 hr, a 28% reduction in CCR4 expression was noted (P < 0.05) among the malignant population with an associated 9% decrease in chemotaxis to TARC (P < 0.05). Our results show that bexarotene may inhibit malignant cell trafficking to the skin through an ability to suppress CCR4 expression among Sezary Syndrome lymphocytes. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc.
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association of change in clinical status and change in the percentage of the cd4 cd26 lymphocyte population in patients with Sezary Syndrome
Journal of The American Academy of Dermatology, 2005Co-Authors: Camille E Introcaso, Stephen D Hess, Malek Kamoun, Ravi Ubriani, Joel M Gelfand, Alain H RookAbstract:Background Because there are currently many effective therapies available for Sezary Syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an intervention. It has been our clinical experience that changes in patients' CD4 + CD26 − T-cell populations of peripheral blood lymphocytes herald changes in their clinical status. Objective Our purpose was to evaluate whether a change in patients' CD4 + CD26 − population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in T-cell populations that are CD4 + CD7 − , CD8 + , CD56 + , and the CD4 + /CD8 + T-cell ratio and a change in the patient's clinical status. Methods We conducted a retrospective chart review analysis of 21 patients with Sezary Syndrome who had flow cytometry, usually including levels of CD4 + CD26 − , CD4 + CD7 − , CD8 + , CD56 + , and CD4 + /CD8 + ratios measured at two time periods, 12 weeks apart. Results We report two cases in which changes in patients' clinical status were preceded by several weeks by a change in their CD4 + CD26 − level. We report weak associations between a decreasing CD4 + CD26 − T-cell population, a decreasing CD4 + CD7 − population, an increasing CD56 + population, and an improving clinical status. We also report stronger associations between both a decreasing CD8 + population and an increasing CD4 + /CD8 + ratio and a worsening clinical status. Limitations The study was limited by the number of patients and the time period over which the study was conducted. In addition, varying configurations of CD4 + CD26 − T-cell populations were observed that may have limited the utility of this measurement. Conclusions Flow cytometry assays of patients' blood and, in particular, measurement of the CD4 + CD26 − population of lymphocytes over time may be a valuable tool for monitoring patients with Sezary Syndrome. There exist varying configurations of CD26 T lymphocytes that may cause differences in standards for what is considered positive and negative between observers. Further prospective analysis involving larger groups of patients is recommended.
Sean Whittaker - One of the best experts on this subject based on the ideXlab platform.
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prognostic factors prognostic indices and staging in mycosis fungoides and Sezary Syndrome where are we now
British Journal of Dermatology, 2014Co-Authors: Julia Scarisbrick, Sean Whittaker, Gary S Wood, Maarten H Vermeer, Youn H Kim, H M Prince, Pietro QuaglinoAbstract:Summary Mycosis fungoides is the most prevalent form of primary cutaneous T-cell lymphoma. Patients frequently present with early-stage disease typically associated with a favourable prognosis and survival of 10–35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sezary Syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA–IIA (early-stage disease) and IIB–IVB (advanced-stage disease) and provides prognostic information, but some patients with tumour-stage disease (IIB) have a worse prognosis than those with erythrodermic-stage (III). Conversely, patients with plaque-stage (IB) folliculotropic mycosis fungoides may have a worse outcome than those with tumour-stage (IIB). The more recent staging system of the European Organisation for the Research and Treatment of Cancer/International Society for Cutaneous Lymphoma has been designed to reflect tumour burden at different sites. However, this staging system has not been validated prospectively for prognosis. Furthermore, this staging system does not include a detailed measurement of skin tumour burden, as indicated by the modified skin weighted severity assessment tool. This assessment measures body surface area of disease and is weighted to record patch, plaque and tumour to produce a numerical value from 0·5 to 400 and is an established endpoint for clinical studies. Nor does this staging include clinicopathological features associated with a poor prognosis such as folliculotropism. Here we review the clinical, haematological, pathological and genotypic parameters outside the staging system, which may affect survival in mycosis fungoides and Sezary Syndrome. Most studies are retrospective and single centre. The identification of poor prognostic factors may be used to develop a prognostic index to use alongside staging, which may be of benefit in mycosis fungoides/Sezary Syndrome to identify patients with a potentially poor prognosis.
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how i treat mycosis fungoides and Sezary Syndrome
Blood, 2009Co-Authors: Miles H Prince, Sean Whittaker, Richard T HoppeAbstract:Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sezary Syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional "stage-based" approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies.
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bexarotene therapy for mycosis fungoides and Sezary Syndrome
British Journal of Dermatology, 2009Co-Authors: R A Abbott, Sean Whittaker, R Russelljones, S L Morris, T Hung, S J Bashir, Julia ScarisbrickAbstract:Summary Background Bexarotene (Targretin®) is a synthetic retinoid which is licensed for the treatment of advanced refractory cutaneous T-cell lymphoma (CTCL). Objectives To summarize our experience with bexarotene for patients with CTCL with the aim of assessing efficacy and safety. Methods A retrospective study of 66 patients (44 male, 22 female) with mycosis fungoides (40 patients) or Sezary Syndrome (26 patients) who were commenced on bexarotene prior to August 2007 was carried out. Nineteen patients had early-stage (IB–IIA) refractory mycosis fungoides and 47 patients had advanced-stage CTCL (IIB–IVB). Results Fifty-two out of 66 (79%) patients completed over 1 month of therapy with an intention-to-treat response rate of 44% (29/66). Of the patients, six (9%) had a complete response, 23 (35%) had a partial response, 15 (23%) had stable disease and eight (12%) had progressive disease. Median time to maximal response was 3 months (1–9 months). Median response duration was 8 months (1 to > 48 months). Median time to progression was 9 months (3–44 months). Fourteen patients (21%) did not complete a month of bexarotene therapy. Adverse effects of the whole group included central hypothyroidism in 100% (all grade II and managed with thyroid replacement) and hyperlipidaemia in 100% (all managed with lipid-lowering therapy ± dose reduction). Responses were seen in all stages and were higher in advanced stages: 26% (five of 19) with early-stage and 51% (24/47) of advanced-stage disease. Responses were seen in skin, blood and lymph nodes. Twenty-eight out of 66 patients were treated with bexarotene monotherapy and the remainder were on one or more additional anti-CTCL therapies. Conclusions Our data demonstrate that bexarotene is well tolerated in most patients and responses are seen in almost half of patients with all disease stages. However partial responses were not graded and would include any improvement seen in the skin, blood and lymph node.
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novel and highly recurrent chromosomal alterations in Sezary Syndrome
Cancer Research, 2008Co-Authors: Maarten H Vermeer, Sean Whittaker, Remco Van Doorn, Remco Dijkman, Xin Mao, Pieter C Van Voorst Vader, M J P Gerritsen, M L Geerts, Sylke Gellrich, Ola SoderbergAbstract:This study was designed to identify highly recurrent genetic alterations typical of Sezary Syndrome (Sz), an aggressive cutaneous T-cell lymphoma/leukemia, possibly revealing pathogenetic mechanisms and novel therapeutic targets. High-resolution array-based comparative genomic hybridization was done on malignant T cells from 20 patients. Expression levels of selected biologically relevant genes residing within loci with frequent copy number alteration were measured using quantitative PCR. Combined binary ratio labeling-fluorescence in situ hybridization karyotyping was done on malignant cells from five patients. Minimal common regions with copy number alteration occurring in at least 35% of patients harbored 15 bona fide oncogenes and 3 tumor suppressor genes. Based on the function of the identified oncogenes and tumor suppressor genes, at least three molecular mechanisms are relevant in the pathogenesis of Sz. First, gain of cMYC and loss of cMYC antagonists (MXI1 and MNT) were observed in 75% and 40% to 55% of patients, respectively, which were frequently associated with deregulated gene expression. The presence of cMYC/MAX protein heterodimers in Sezary cells was confirmed using a proximity ligation assay. Second, a region containing TP53 and genome maintenance genes (RPA1/HIC1) was lost in the majority of patients. Third, the interleukin 2 (IL-2) pathway was affected by gain of STAT3/STAT5 and IL-2 (receptor) genes in 75% and 30%, respectively, and loss of TCF8 and DUSP5 in at least 45% of patients. In sum, the Sz genome is characterized by gross chromosomal instability with highly recurrent gains and losses. Prominent among deregulated genes are those encoding cMYC, cMYC-regulating proteins, mediators of MYC-induced apoptosis, and IL-2 signaling pathway components.
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extracorporeal photopheresis in Sezary Syndrome no significant effect in the survival of 44 patients with a peripheral blood t cell clone
Archives of Dermatology, 1998Co-Authors: Elisabeth A Fraserandrews, Sean Whittaker, Paul T. Seed, R RusselljonesAbstract:Background Several retrospective studies have claimed that extracorporeal photopheresis (ECP) prolongs survival in patients with erythrodermic cutaneous T-cell lymphoma. In a retrospective study of 44 patients with Sezary Syndrome, we compared survival in patients treated with ECP with that of patients treated conventionally at the same institute. All patients had genotypic evidence of a peripheral blood T-cell clone. Observations Twenty-nine patients received ECP (group 1); 15 patients did not receive ECP, 8 patients when ECP was available (group 2) and 7 before ECP was available (group 3). Forty-three of 44 patients received other conventional treatments. Median survival from diagnosis of Sezary Syndrome was 39 months in group 1, 22 months in group 2, and 27.5 months in group 3 (Kaplan-Meier analysis). Cox regression analysis showed no significant difference between the 3 groups after correcting for age, sex, and initial Sezary cell count (hazard ratio, 0.56; 95% confidence interval, 0.26-1.17; P =.12). Conclusions This study does not support the contention that ECP prolongs survival in patients with Sezary Syndrome. The median survival in the ECP-treated group is considerably less than that reported in other published series, possibly because genotypic evidence of clonality in the peripheral blood was required for inclusion in this study. We believe that a randomized trial comparing ECP with standard chemotherapy is urgently needed.
