RESUMO
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
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Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Síndrome de Sézary/terapia , Síndrome de Sézary/patologia , Consenso , Qualidade de Vida , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Fatores Imunológicos/uso terapêuticoRESUMO
Extracorporeal photopheresis (ECP) has gained importance in the treatment of several diseases. Initially introduced as a new therapeutic modality for the treatment of patients with cutaneous T-cell lymphoma, the indications for the use of ECP have expanded to include hematology and transplantation immunology. Extracorporeal photopheresis has found its place in the treatment plan of cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease, organ transplantation such as heart and lung, sometimes as first-line therapy and very often in combination with various systemic immunosuppressive therapies. The procedure basically consists of three steps: leukapheresis, photoactivation and reinfusion. The following article presents possible theories about the mechanism of action, which is not yet fully understood, and discusses the five most common indications for ECP treatment with corresponding therapy recommendations.
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Doença Enxerto-Hospedeiro , Linfoma Cutâneo de Células T , Fotoferese , Escleroderma Sistêmico , Neoplasias Cutâneas , Humanos , Fotoferese/métodos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Linfoma Cutâneo de Células T/terapia , Neoplasias Cutâneas/terapiaRESUMO
Haematopoietic stem cell transplantation (HSCT) is the treatment of choice for malignant haematological diseases. Despite continuous improvements in pre- and post-transplantation procedures, the applicability of allo-HSCT is limited by life-threatening complications such as graft-versus-host disease (GvHD), engraftment failure, and opportunistic infections. Extracorporeal photopheresis (ECP) is used to treat steroid resistant GvHD with significant success. However, the molecular mechanisms driving its immunomodulatory action, whilst preserving immune function, require further understanding. As ECP is safe to administer with few significant adverse effects, it has the potential for earlier use in the post-HSCT treatment of GvHD. Thus, further understanding the immunomodulatory mechanisms of ECP action may justify more timely use in clinical practice, as well as identify biomarkers for using ECP as first line or pre-emptive GvHD therapy. This review aims to discuss technical aspects and response to ECP, review ECP as an immunomodulatory treatment modality for chronic GvHD including the effect on regulatory T cells and circulating vs. tissue-resident immune cells and consider the importance of emerging biomarkers for ECP response.
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Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Fotoferese , Humanos , Biomarcadores , ImunidadeRESUMO
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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Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Humanos , Estudos Prospectivos , Micose Fungoide/patologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , BiópsiaRESUMO
In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8-10 ng/ml, months 1-6; 5-8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (n = 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.
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Transplante de Coração , Fotoferese , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Humanos , Terapia de Imunossupressão , Imunossupressores , Fotoferese/métodos , Projetos PilotoRESUMO
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
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Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Ensaios Clínicos como Assunto , Humanos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/terapia , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Micose Fungoide/terapia , Estadiamento de Neoplasias , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/patologia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Estados UnidosRESUMO
Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients' health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.
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Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Humanos , Micose Fungoide , Qualidade de Vida , Síndrome de SézaryRESUMO
Graft-versus-host disease (GvHD) is a commonly occurring immunological reaction and frequent complication following allogeneic hematopoietic stem cell transplantation. Its highly diverse manifestations including skin involvement as the most common appearance of GvHD, can dramatically influence patient's quality of life, in particular in the chronic stage, in addition to patient's decreased survival outcome. Hence, the role of the dermatologist has become very crucial in an interdisciplinary setting, particularly since appearances of GvHD in the skin can be multifaceted and challenging. Clinical manifestation of the acute GvHD (aGvHD) is limited to erythematous maculopapular rash and oral mucosal lesions while the chronic form manifests in a wider range in a localized area or disseminated including involvement of nail, scalp and genital area. This article aims to provide a comprehensive overview on the variable cutaneous presentations of acute and chronic GvHD for a proper and early diagnosis on the one hand, and to discuss updated therapeutic options for both acute and chronic GvHD on the other hand, to initiate an adequate treatment to obtain the most beneficial clinical outcome.
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Doença Enxerto-Hospedeiro/fisiopatologia , Dermatopatias/fisiopatologia , Pele/fisiopatologia , Doença Aguda , Doença Crônica , Dermatologistas/organização & administração , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Papel do Médico , Qualidade de Vida , Dermatopatias/etiologia , Dermatopatias/terapiaRESUMO
Introduction: The National Comprehensive Cancer Network and the European Organization for Research and Treatment of Cancer recommend extracorporeal photopheresis (ECP) as systemic therapy for cutaneous T-cell lymphoma (CTCL).Objective: To investigate real-world use of ECP in CTCL patients in the US.Methods: Data from the Truven MarketScan® database (2010-2015) were used to create a cohort of CTCL patients receiving systemic treatment. Multivariable regressions were performed to compare health care resource utilization between ECP and propensity score-matched non-ECP patients.Results: Of the 1106 eligible patients, 117 (10.6%) received ECP, with an average treatment duration of 13.6 months. Psoriasis, organ transplant, graft versus host disease, and scleroderma were the most common comorbidities. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35.0%), mostly with interferon and/or a retinoid. Higher Charlson Comorbidity Index (2.6 vs 2.2, p < .05), rates of organ transplant (49.6% vs 7.8%, p < .001), and graft vs host disease (41.9% vs 3.4%, p < .001) were observed in ECP versus non-ECP patients. Post-matching analyses showed that ECP patients had shorter all-cause inpatient stay (6.67 vs 11.80 days, p = .001).Conclusions: Approximately 1 out of 10 CTCL patients receiving systemic treatment were on ECP treatment in the US. Post-matching analysis showed ECP was associated with a shorter hospital stay.
Assuntos
Linfoma Cutâneo de Células T/terapia , Fotoferese , Adolescente , Adulto , Idoso , Comorbidade , Bases de Dados Factuais , Circulação Extracorpórea , Feminino , Humanos , Interferons/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Retinoides/uso terapêutico , Estados Unidos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Pyogenic granuloma is a common benign vascular lesion of the skin and mucosa prone to ulceration and bleeding. Current therapeutic approaches include surgical excision, removal by means of electro caustic therapy, cryotherapy, and ablation with CO2 or vascular lasers. The purpose of this study was to investigate the efficacy of a 532 nm potassium-titanyl-phosphate laser (KTP-laser) for the treatment of pyogenic granulomas in terms of efficacy, advantages in clinical outcome, technique and associated side effects. METHODS: In this retrospective study we report on the response of 28 consecutive patients with pyogenic granulomas at multiple locations on the skin after having been treated with a 532 nm KTP laser (532 nm AuraTM Star Pulse laser, Laserscope, CA, USA). Treatment was performed with a 2 mm handpiece and energy fluences of 35-60 J cm-2 and a laser pulse width of 50 ms or with a 1 mm handpiece and energy fluences of 200-240 J cm-2 and a laser pulse width of 50 ms. All patients were treated on an outpatient basis at the department of dermatology, Medical University of Vienna, Austria. RESULTS: In all of the 28 patients treated, we were able to demonstrate both symptomatic and clinical clearing of the lesions with excellent cosmetic results after the treatment. In 25 of the 28 patients a single treatment was sufficient to obtain optimal results. In three patients a second treatment session was required due to the recurrence of the lesion. The procedure required only local anesthesia, and postoperative care was limited to the application of a topical antibiotic ointment. No postoperative complications such as increased pain or wound infection and only minimal scarring were observed. CONCLUSIONS: This experience with excellent patient satisfaction suggests that treatment of pyogenic granulomas with the KTP laser is a safe, effective, and reasonable alternative to conventional therapy. As with many other limited interventions with this laser technology, the advantages include minimal postoperative pain, conservative site-specific minimally invasive surgeries and a very satisfactory cosmetic result with a high acceptance rate on the side of the patients.
Assuntos
Granuloma Piogênico/terapia , Terapia a Laser , Lasers de Estado Sólido , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fosfatos , Potássio , Estudos Retrospectivos , Titânio , Adulto JovemRESUMO
Extracorporeal photopheresis (ECP) has been in clinical use for over three decades after receiving FDA approval for the palliative treatment of the Sézary Syndrome variant of cutaneous T-cell lymphoma (CTCL) in 1988. After the first positive experiences with CTCL, additional indications have been successfully explored including areas such as graft-vs.-host disease (GVHD), scleroderma, and solid organ transplantation. The mechanism of action is still not fully resolved, but important steps in understanding ECP in recent years have been very informative. Originally, the primary hypothesis stated that psoralen and ultraviolet A (UVA) in combination induce apoptosis in the treated immune cells. This view shifted in favor of dendritic cell initiation, modification of the cytokine profile and stimulation of several T-cell lineages, in particular regulatory T-cells. A number of ECP guidelines have been produced to optimize treatment regimens in the clinical context. In CTCL, enough evidence is available for the use of ECP as a first line treatment for Sézary Syndrome (SS), but also as a second line or rescue treatment in therapy-refractory forms of mycosis fungoides (MF). ECP in the treatment of acute and chronic GVHD has shown promising results as second line therapy in steroid-refractory presentations. In solid organ transplantation, ECP has been used to increase tissue tolerance and decrease infections with opportunistic pathogens, attributed to the use of high doses of immunosuppressive medication. Infection with cytomegalovirus (CMV) remains a limiting factor affecting survival in solid organ transplantation and the role of ECP will be discussed in this review. A trend toward prophylactic use of ECP can be observed and may further contribute to improve the outcome in many patients. To further deepen our knowledge of ECP and thus facilitate its use in patients that potentially benefit most from it, future prospective randomized trials are urgently needed in this rapidly growing field. The aim of this review is to (1) introduce the method, (2) give an overview where ECP has shown promising effects and has become an essential part of treatment protocols, and (3) to give recommendations on how to proceed in numerous indications.
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Our current mycosis fungoides (MF) and Sézary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sézary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry. No large study comparing blood-class as defined by Sézary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p < 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis. For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4+CD7-or CD4+CD26-where B0<250/µL, B1 = 250/µl-<1000/µL and B2≥1000/µL plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known.
Assuntos
Citometria de Fluxo/métodos , Linfoma/patologia , Micose Fungoide/patologia , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Humanos , Linfoma/sangue , Linfoma/classificação , Micose Fungoide/sangue , Micose Fungoide/classificação , Estadiamento de Neoplasias , Síndrome de Sézary/sangue , Síndrome de Sézary/classificação , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/classificaçãoRESUMO
The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL). Illness perception reflects patients' individual concepts of understanding and interpretation of the disease, influencing illness behaviour and health-related quality of life (HRQOL). This study investigated the clinical relevance of the relationships between illness perception, illness behaviour, and HRQOL in CTCL and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ-R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to illness perception, whereas illness perception was significantly associated with HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and socio-demographics. Only IPQ-R results provided practical information on patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and CBCL might be a useful instrument to improve individual disease management.
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Conhecimentos, Atitudes e Prática em Saúde , Comportamento de Doença , Linfoma de Células B/psicologia , Linfoma Cutâneo de Células T/psicologia , Pacientes/psicologia , Percepção , Neoplasias Cutâneas/psicologia , Adulto , Idoso , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/terapia , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Inquéritos e QuestionáriosRESUMO
Graft-versus-host disease (GVHD) is an immunological reaction and a frequent complication following allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and may have a significant negative impact on the patient's quality of life, particularly in the chronic-stage setting. Many different organs can be involved, which leads to a wide range of clinical manifestations. In this context, dermatologists play a key role by diagnosing and treating GVHD from the outset since cutaneous features are not just the most common but are also usually the presenting sign. Several skin-direct therapies are available and may be indicated as monotherapy or adjuvant treatment in order to allow faster tapering and withdrawal of systemic immunosuppression. Treatment of steroid-refractory patients remains a challenge and, to date, no consensus has been reached for one single agent in second-line therapy. This article aims to review skin involvement as well as provide and update discussion on therapeutic options for both acute and chronic cutaneous GVHD.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia de Imunossupressão/métodos , Dermatopatias/terapia , Doença Aguda/terapia , Administração Cutânea , Administração Intravenosa , Administração Oral , Biomarcadores/análise , Doença Crônica/terapia , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Qualidade de Vida , Pele/imunologia , Dermatopatias/diagnóstico , Dermatopatias/imunologia , Dermatopatias/mortalidadeRESUMO
EORTC 21081 was a randomized phase III study of observation alone versus lenalidomide maintenance (25 mg po for 21 days) after debulking therapy in patients with advanced-stage cutaneous T-cell lymphomas (CTCLs). The aim was to investigate whether maintenance treatment with lenalidomide prolonged response after debulking in patients who had not been previously treated with intravenous chemotherapy. A total of 26 centres from 10 different European countries registered 30 patients with advanced CTCL. Twenty-one patients were randomized (20% of the 105 patients initially deemed necessary for the study; the study was terminated early following withdrawal of funding support from Celgene). Of 30 registered patients, nine failed to be randomized, 12 were randomized to observation alone, and nine to lenalidomide maintenance. Median progression-free survival was 5.3 months (95% CI: 1.87-22.54) in the maintenance lenalidomide group and two months (95% CI: 0.92-7.82) in the observation alone group. Although statistical comparison in the study was severely underpowered and would not be meaningful, this study provides useful information, revealing rapid disease progression within four weeks in a third of patients, highlighting the need for maintenance therapy.
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Inibidores da Angiogênese/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/cirurgia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Talidomida/análogos & derivados , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Talidomida/uso terapêuticoRESUMO
In order to provide a common standard for the treatment of mycosis fungoides (MF) and Sézary syndrome (SS), the European Organisation for Research and Treatment of Cancer-Cutaneous Lymphoma Task Force (EORTC-CLTF) published in 2006 its consensus recommendations for the stage-adapted selection of management options for these neoplasms. Since then, the understanding of the pathophysiology and epidemiology of MF/SS has advanced, the staging system has been revised, new outcome data have been published and novel treatment options have been introduced. The purpose of the present document is to update the original recommendations bearing in mind that there are still only a limited number of controlled studies to support treatment decisions for MF/SS and that often treatment is determined by institutional experience and availability. This consensus on treatment recommendations was established among the authors through a series of consecutive consultations in writing and a round of discussion. Recommended treatment options are presented according to disease stage, whenever possible categorised into first- and second-line options and supported with levels of evidence as devised by the Oxford Centre for Evidence-Based Medicine (OCEBM). Skin-directed therapies are still the most appropriate option for early-stage MF, and most patients can look forward to a normal life expectancy. For patients with advanced disease, prognosis is still grim, and only for a highly selected subset of patients, prolonged survival can be achieved with allogeneic stem cell transplantation (alloSCT). There is a high need for the development and investigation in controlled clinical trials of treatment options that are based on our increasing understanding of the molecular pathology of MF/SS.
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Micose Fungoide/terapia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Biológicos/uso terapêutico , Terapia Combinada/métodos , Consenso , Fármacos Dermatológicos/uso terapêutico , Elétrons/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Imunoterapia/métodos , Interferon-alfa/uso terapêutico , Micose Fungoide/patologia , Estadiamento de Neoplasias , Fototerapia/métodos , Guias de Prática Clínica como Assunto , Retinoides/uso terapêutico , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Conduta ExpectanteRESUMO
PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). RESULTS: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). CONCLUSION: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.
Assuntos
Modelos Estatísticos , Micose Fungoide/mortalidade , Micose Fungoide/patologia , Síndrome de Sézary/mortalidade , Síndrome de Sézary/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto , Fatores Etários , Idoso , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Micose Fungoide/metabolismo , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Síndrome de Sézary/metabolismo , Pele/enzimologia , Neoplasias Cutâneas/metabolismo , Taxa de SobrevidaRESUMO
Graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. In the skin, GVHD can present in an acute (aGVHD), chronic lichenoid (clGVHD), or chronic sclerotic form (csGVHD). Measuring peripheral blood levels of the keratinocyte-derived protease inhibitor elafin has recently emerged as a promising tool for the diagnosis of cutaneous aGVHD. We evaluated whether the analysis of elafin expression in skin would allow distinguishing aGVHD from drug hypersensitivity rashes (DHR) and whether cutaneous elafin expression would correlate with disease severity or altered prognosis of aGVHD and clGVHD/csGVHD. Skin biopsies from aGVHD (n=22), clGVHD (n=15), csGVHD (n=7), and DHR (n=10) patients were collected and epidermal elafin expression and its association with diverse clinical/histological parameters were analyzed. Acute GVHD and DHR displayed varying degrees of elafin expression. No elafin was detectable in csGVHD, whereas the molecule was increased in clGVHD as compared with aGVHD. Elafin-high aGVHD/clGVHD lesions presented with epidermal thickening and were associated with poor prognosis-i.e., decreased overall survival in aGVHD and corticosteroid resistance in clGVHD. Although cutaneous elafin does not seem to discriminate aGVHD from DHR lesions, our study strongly suggests an association between cutaneous elafin expression and poor prognosis for patients with cutaneous GVHD.