EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.

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.

Eficacia y seguridad de una alternativa a la terapia hormonal de la menopausia: extracto purificado de polen / Efficacy and safety of an alternative to menopausal hormone therapy: purified cytoplasm of pollen

Los síntomas vasomotores (SVM) se encuentran entre los síntomas más comunes de la transición a la menopausia. Más del 70% de las mujeres de mediana edad informan SVM en algún momento durante la transición a la menopausia, y para un tercio de las mujeres los SVM son muy frecuentes o graves. Muchas mujeres recurren a terapias naturales para tratar los SVM. Esta revisión se centra en una de esas opciones naturales: el extracto purificado de polen (Serelys®). Se realizó una búsqueda e identificación de artículos publicados hasta octubre de 2022 recopilados de sistemas de búsqueda electrónicos, como Google Scholar, MEDLINE, PubMed y Scopus. Las palabras de búsqueda fueron “Vasomotor symptoms”, “menopause” AND “pollen”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre los SVM.

Vasomotor symptoms (VMS) are among the most common symptoms of the menopausal transition. More than 70% of middle-aged women report VMS at some point during the menopausal transition, and for a third of women, VMS is very common or severe. Many women turn to natural therapies to treat VMS. This review focuses on one such natural option, purified pollen extract (Serelys®). The information available until October 2022 was collected via the library and electronic search systems such as Google Scholar, MEDLINE, PubMed, and Scopus. The search words were: “Vasomotor symptoms”, “menopause” AND “pollen”. Preclinical studies point to a mechanism of action in its involvement in the serotonergic system, as well as its binding to dopamine receptors. Clinical studies demonstrate the safety and positive effect on VMS.

Hematic Antegrade Repriming: A Reproducible Method to Decrease the Cardiopulmonary Bypass Insult.

The current practice of cardiopulmonary bypass (CPB) requires a preoperative priming of the circuit that is frequently performed with crystalloid solutions. Crystalloid priming avoids massive embolism but is unable to eliminate all microbubbles contained in the circuit. In addition, it causes a sudden hemodilution which is correlated with transfusion requirements and an increased risk of cognitive impairment. Several repriming techniques using autologous blood, collectively termed retrograde autologous priming (RAP), have been demonstrated to reduce the hemodilutional impact of CPB. However, the current heterogeneity in the practice of RAP limits its evidence and benefits. Here, we describe hematic antegrade repriming as an easy and reliable method that could be applied with any circuit in the market to decrease transfusion requirements, emboli, and inflammatory responses, reducing costs and the impact of CPB on postoperative recovery.

Cost of early-stage mycosis fungoides treatments in Spain.

AIM: To identify the most common therapeutic options for the treatment of early-stage mycosis fungoides in Spain, quantify their associated healthcare resource use and costs. METHODS: After reviewing the literature, a panel of 6 Spanish clinical dermatologists validated the treatments and healthcare resource use through a structured questionnaire. Individual responses were collected, analyzed and presented into a face-to-face meeting in order to reach a consensus. Cost categories considered were: drug acquisition and administration, photo/radiotherapy session and maintenance, clinical follow-up visits and laboratory tests. Costs were expressed in euros from 2018. The Spanish National Health System perspective was considered, taking into account direct health costs and time horizons of 1, 3 and 6 months. RESULTS: Costs for the skin-directed treatments (SDT) assessed at 1, 3 and 6 months, were: Topical carmustine [€6,593.36, €19,780.09 and €27,592.78]; Phototherapy with psoralens and ultraviolet A light (PUVA) [€1,098.68, €2,999.99 and €3,187.60]; Narrow-band ultraviolet B phototherapy [€1,657.47, €4,842.10 and €4,842.10]; Total skin electron beam therapy (TSEBT) [€6,796.45, €7,913.34 and €7,913.34]. Cost for topical corticosteroids, being considered an adjuvant option, were €17.16, €51.49 and €102.97. Costs for the assessed systemic treatments alone or in combination with SDT at 1, 3 and 6 months, were: Systemic retinoids [€2,026.03, €5,206.63 and €7,426.42]; Systemic retinoids + PUVA phototherapy [€3,066.50, €8,271.26 and €10,046.58]; Interferon alfa + PUVA phototherapy [€1,541.09, €5,167.57 and €6,404.55]. CONCLUSION: According to the Spanish clinical practice, phototherapies in monotherapy were the treatments with the lowest associated costs regardless of the time horizon considered. TSEBT turned out as the treatment with the highest associated costs when considering 1 month. However, while considering 3 and 6 months the treatment with the highest associated costs was topical carmustine. The results of this analysis may provide critical information to measure the disease burden, to detect unmet medical needs and to advocate towards better treatments for this rare disease.

Omalizumab as an alternative therapeutic tool in the treatment of bullous pemphigoid: A case report.

Bullous pemphigoid (BP) is an acquired autoimmune bullous disease characterized by autoantibodies against the hemidesmosomal proteins found in the basal keratinocytes of the basement membrane zone (BMZ): a 180 kDa protein (type XVII collagen) mainly and the 230 kDa antigen. There is such evidence that the antibodies against the BMZ components are not only of IgG type, but also this bullous disease may have IgE antibodies directed to the BMZ that contribute to the pathogenesis of the disorder. IgE is not only thought to contribute to the pathogenesis of BP, it has also been suggested that eosinophils play a role in the development of the first signs associated with BP. A humanized monoclonal antibody directed to IgE, omalizumab, is approved for the treatment of severe asthma and chronic spontaneous urticaria, and it may be useful in the treatment of BP in the first stages of the disease.

European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2017.

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.

Primary cutaneous marginal zone B-cell lymphoma: response to treatment and disease-free survival in a series of 137 patients.

BACKGROUND: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. OBJECTIVE: We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. METHODS: Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. RESULTS: Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. LIMITATIONS: This was a case series retrospective study. CONCLUSION: Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.

[Treatment of mycosis fungoides with PUVA and bexarotene]. / Tratamiento de micosis fungoide con PUVA más bexaroteno.

INTRODUCTION: The combined use of bexarotene and PUVA is a treatment that is currently being investigated. In this paper, six patients treated with this combination are presented. OBJECTIVES: To assess the efficacy and safety of treatment with PUVA + bexarotene in patients with mycosis fungoides (MF). Patients, material and methods. Six patients diagnosed with MF in different stages, who received three sessions of PUVA treatment a week (initially 2.35 J/cm 2, with progressive increases to a maximum of 23.5 J/cm 2) + bexarotene (initial dose 300 mg/m 2/day, decreasing to 200, 150 or 75 mg/m 2 if signs of toxicity appeared). All received atorvastatin. RESULTS: Stage at the start of treatment: two patients IIb, one patient Ib with B2 blood involvement, two patients Ib, one patient Ia. Five of the six patients responded to the treatment (three full remissions [FR], two partial remissions [PR]). One patient did not respond. In those in whom FR was achieved, the time required for the response was 10, 20 and 24 weeks. All presented with hypertriglyceridemia (maximum 1194 mg/ dL). It was necessary to administer thyroid hormone supplements to four of the patients. Two of them had alterations in the hepatic biochemistry values, and two others presented with alterations in the muscle profile analysis. CONCLUSION: The combination of PUVA and bexarotene is a safe and effective treatment for MF. It will be necessary to await the results of the clinical trials currently underway to see if their combined use is better than treatment with PUVA alone. The response rate (RR) was 86 % (three FR and two PR out of six patients).

Tratamiento de micosis fungoide con PUVA más bexaroteno / Treatment of mycosis fungoides with PUVA and bexarotene

Introducción. La utilización conjunta de bexaroteno y psoraleno y radiación ultravioleta A (PUVA) en la actualidad es un tratamiento en investigación. En el presente trabajo se presentan 6 pacientes tratados con esta combinación. Objetivos. Valorar eficacia y seguridad del tratamiento con PUVA más bexaroteno en pacientes con micosis fungoide. Pacientes, material y métodos. Seis pacientes diagnosticados de micosis fungoide en distintos estadios que han recibido PUVA, tres sesiones semanales (inicio 2,35 J/cm 2, con aumentos progresivos hasta llegar a un máximo de 23,5 J/cm 2) más bexaroteno (dosis inicial, 300 mg/m 2/día, disminuyendo a 200, 150 o 75 mg/m 2 si aparecía toxicidad). Todos los pacientes recibieron atorvastatina. Resultados. Al inicio de tratamiento, 2 pacientes se encontraban en estadio IIb, un paciente en Ib con afectación hemática B2, 2 pacientes en Ib y un paciente en estadio Ia. Cinco de los 6 pacientes respondieron al tratamiento (tres remisiones completas [RC], dos remisiones parciales [RP]). Un paciente no respondió. De los que obtuvieron RC, el tiempo hasta la respuesta fue de 10, 20 y 24 semanas, respectivamente. Todos los pacientes presentaron hipertrigliceridemia (máximo de 1.194 mg/dl). En cuatro de los pacientes fue necesario administrar suplementos de hormona tiroidea. Dos de ellos tuvieron alteraciones de la bioquímica hepática y dos más presentaron alteraciones analíticas del perfil muscular. Conclusión. La combinación de PUVA y bexaroteno es un tratamiento eficaz y seguro para la micosis fungoide. Habrá que esperar a los resultados de los ensayos clínicos en curso para ver si es mejor su uso combinado que el tratamiento con PUVA sola. El índice de respuesta fue del 86 % (3 RC y 2 RP de 6 pacientes)

Introduction. The combined use of bexarotene and PUVA is a treatment that is currently being investigated. In this paper, six patients treated with this combination are presented. Objectives. To assess the efficacy and safety of treatment with PUVA + bexarotene in patients with mycosis fungoides (MF). Patients, material and methods. Six patients diagnosed with MF in different stages, who received three sessions of PUVA treatment a week (initially 2.35 J/cm 2, with progressive increases to a maximum of 23.5 J/cm 2) + bexarotene (initial dose 300 mg/m 2/day, decreasing to 200, 150 or 75 mg/m 2 if signs of toxicity appeared). All received atorvastatin. Results. Stage at the start of treatment: two patients IIb, one patient Ib with B2 blood involvement, two patients Ib, one patient Ia. Five of the six patients responded to the treatment (three full remissions [FR], two partial remissions [PR]). One patient did not respond. In those in whom FR was achieved, the time required for the response was 10, 20 and 24 weeks. All presented with hypertriglyceridemia (maximum 1194 mg/ dL). It was necessary to administer thyroid hormone supplements to four of the patients. Two of them had alterations in the hepatic biochemistry values, and two others presented with alterations in the muscle profile analysis. Conclusion. The combination of PUVA and bexarotene is a safe and effective treatment for MF. It will be necessary to await the results of the clinical trials currently underway to see if their combined use is better than treatment with PUVA alone. The response rate (RR) was 86 % (three FR and two PR out of six patients)

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome.

Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.

[Usefulness of scintigraphy images with 111In-CYT-103 in the diagnosis of colonic and rectal recurrence]. / Utilidad de las imágenes centelleográficas con 111In.CYT-103 en el diagnóstico de recurrencia del cáncer de colon y recto.

OBJECTIVE: To determine the effectiveness of radioimmunoscintigraphy (RIC) with 111In-CYT-103 in detecting the extension of malignant disease in patients surgically treated for colorectal adenocarcinoma under suspicion of recurrence in comparison to CT scan (computed tomography) and exploratory laparotomy. DESIGN: Prospective and observational study. MATERIAL AND METHODS: A total of 26 patients under suspicion of recurrence, with a total of 31 lesions. All the patients had performed the following studies with GT, RIC with 111In-CYT-103, exploratory laparotomy and histopathology. RESULTS: A sensitivity of 96.8%, and specificity of 77.8%, and accuracy of 92% were found for the RIC. CT scan had a sensitivity, specificity and accuracy of 71.5%, 88.8%, and 75.7%, respectively in extrahepatic lesions. When both methods are combined, results shows an increment in sensitivity. Hepatic lesions were present in 50% of the patients; a sensitivity of 85%, a specificity of 92%, and accuracy of 89% for RIC and sensitivity, specificity and accuracy of 92% for the CT. CONCLUSION: The results of clinical studies with 111In-CYT-103 in detecting the occurrence of colorectal carcinoma provided additional information, making this method a valuable complementary test that contributes to patient management.

Utilidad de las imágenes centelleográficas con 111In. CYT-103 en el diagnóstico de recurrencia del cáncer de colon y recto / Usefulness of scintigraphy images with 111In-CYT-103 in the diagnosis of colonic and rectal recurrence

OBJECTIVE: To determine the effectiveness of radioimmunoscintigraphy (RIC) with 111In-CYT-103 in detecting the extension of malignant disease in patients surgically treated for colorectal adenocarcinoma under suspicion of recurrence in comparison to CT scan (computed tomography) and exploratory laparotomy. DESIGN: Prospective and observational study. MATERIAL AND METHODS: A total of 26 patients under suspicion of recurrence, with a total of 31 lesions. All the patients had performed the following studies with GT, RIC with 111In-CYT-103, exploratory laparotomy and histopathology. RESULTS: A sensitivity of 96.8, and specificity of 77.8, and accuracy of 92 were found for the RIC. CT scan had a sensitivity, specificity and accuracy of 71.5, 88.8, and 75.7, respectively in extrahepatic lesions. When both methods are combined, results shows an increment in sensitivity. Hepatic lesions were present in 50 of the patients; a sensitivity of 85, a specificity of 92, and accuracy of 89 for RIC and sensitivity, specificity and accuracy of 92 for the CT. CONCLUSION: The results of clinical studies with 111In-CYT-103 in detecting the occurrence of colorectal carcinoma provided additional information, making this method a valuable complementary test that contributes to patient management.

Etiopatogenia de los linfomas cutáneos de células T (micosis fungoide/síndrome de sézary) / Etiophatogenesis of cutaneous T-cell lymphomas (mycosis fungoides/Sézary syndrome)

La micosis fungoide y el síndrome de Sézary son los linfomas cutáneos de células T más frecuentes. Su etiopatogenia es poco conocida, como tampoco se conocen los mecanismos por los que las fases indolentes se hacen más agresivas desarrollan tumores y se afectan ganglios y órganos internos. Se revisan los factores implicados en su desarrollo y evolución: herencia, contaminantes ambientales, agentes infecciosos, antígenos del complejo mayor de histocompatibilidad, inestabilidad genética, citocinas y oncógenes. Aunque el desarrollo de avanzadas técnicas de laboratorio ha aumento el conocimiento de su etiopatogénesis, el signicado de muchos de los factores implicados es controvertido y objeto de debate. Serán necesarios nuevos estudios basados en la epidemiología y en la biología molecular para profundizar en estas cuestiones y en un mayor conocimiento de esta enfermedad (AU)