RESUMO
We present laboratory measurements showing the two-dimensional (2D) structure of energy conversion during magnetic reconnection with a guide field over the electron and ion diffusion regions, resolving the separate energy deposition on electrons and ions. We find that the electrons are energized by the parallel electric field at two locations, at the X line and around the separatrices. On the other hand, the ions are energized ballistically by the perpendicular electric field in the vicinity of the high-density separatrices. An energy balance calculation by evaluating the terms of the Poynting theorem shows that 40% of the magnetic energy is converted to particle energy, 2/3 of which is transferred to ions and 1/3 to electrons. Further analysis suggests that the energy deposited on particles manifests mostly in the form of thermal kinetic energy in the diffusion regions.
RESUMO
The lower hybrid drift wave (LHDW) has been a candidate for anomalous resistivity and electron heating inside the electron diffusion region of magnetic reconnection. In a laboratory reconnection layer with a finite guide field, quasielectrostatic LHDW (ES-LHDW) propagating along the direction nearly perpendicular to the local magnetic field is excited in the electron diffusion region. ES-LHDW generates large density fluctuations (δn_{e}, about 25% of the mean density) that are correlated with fluctuations in the out-of-plane electric field (δE_{Y}, about twice larger than the mean reconnection electric field). With a small phase difference (â¼30°) between two fluctuating quantities, the anomalous resistivity associated with the observed ES-LHDW is twice larger than the classical resistivity and accounts for 20% of the mean reconnection electric field. After we verify the linear relationship between δn_{e} and δE_{Y}, anomalous electron heating by LHDW is estimated by a quasilinear analysis. The estimated electron heating is about 2.6±0.3 MW/m^{3}, which exceeds the classical Ohmic heating of about 2.0±0.2 MW/m^{3}. This LHDW-driven heating is consistent with the observed trend of higher electron temperatures when the wave amplitude is larger. Presented results provide the first direct estimate of anomalous resistivity and electron heating power by LHDW, which demonstrates the importance of wave-particle interactions in magnetic reconnection.
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Use of surrogate end-points such as progression-free survival (PFS) and other time-to-event (TTE) end-points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end-points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co-primary end-point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38-0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30-0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42-0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.
Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Biomarcadores/análise , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Over the past decade, 2 strategies have advanced the treatment of patients with multiple myeloma and its precursor diseases. First, the definition has changed to include patients without end organ damage, who previously would not have been treated. Second, there is widespread enthusiasm for treating high-risk, smoldering multiple myeloma. In this commentary, we explore the evidence supporting these therapeutic expansions. Although early treatment adds cost and therapeutic burden, it remains unknown whether survival and health-related quality of life are improved by early treatment. Herein, we consider the implications of diagnostic expansion in multiple myeloma.
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Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo Latente/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Assintomáticas , Efeitos Psicossociais da Doença , Dexametasona/administração & dosagem , Progressão da Doença , Detecção Precoce de Câncer , Humanos , Cadeias Leves de Imunoglobulina/análise , Fatores Imunológicos/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/economia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/economia , Proteínas do Mieloma/análise , Inibidores de Proteases/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Mieloma Múltiplo Latente/classificação , Mieloma Múltiplo Latente/tratamento farmacológico , Mieloma Múltiplo Latente/economia , Tempo para o TratamentoRESUMO
OBJECTIVES: Patients with multiple myeloma (MM) enrolled in randomized control trials (RCTs) discontinue treatment for various reasons; however, no prior study has analyzed reasons for discontinuation. We performed a systematic review of MM RCTs to investigate reasons for treatment discontinuation, imbalances between trial cohorts, and reporting practices. METHODS: A comprehensive search for RCTs in MM from 2015 to 2021 identified 45 studies meeting inclusion criteria. RESULTS: Of 21 236 randomized patients, 10 161 (47.8%) discontinued therapy by primary endpoint ascertainment. Causes of discontinuation included progression (n = 4790; 22.6% of randomized patients); toxicity (n = 2569; 12.1%); patient/physician withdrawal (n = 1200; 5.7%) and death (n = 495; 2.3%). Of randomized patients, 20 914 (98.5%) were included in the RCT analysis. Imbalances of attrition, defined as trials with greater than 5% absolute difference in discontinuation rate for reasons other than death, progression, and toxicity between intervention and control arms, were found in 11 (24.4%) studies. CONCLUSIONS: Although progression is the most common reason for RCT treatment discontinuation in patients with MM, over 10% discontinued due to toxicity. Furthermore, 24.4% of trials showed substantial imbalances between trial cohorts; raising concern for informative censoring and emphasizes the importance of detailed characterization of withdrawal in MM RCTs.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.
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Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Adulto , Antifúngicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes , Estudos de Coortes , Humanos , Infecções Fúngicas Invasivas/epidemiologia , Leucemia Mieloide Aguda/complicações , Estudos Retrospectivos , SulfonamidasRESUMO
Erdheim-Chester disease (ECD) is a rare histiocytosis that was recently recognized as a neoplastic disorder owing to the discovery of recurrent activating MAPK (RAS-RAF-MEK-ERK) pathway mutations. Typical findings of ECD include central diabetes insipidus, restrictive pericarditis, perinephric fibrosis, and sclerotic bone lesions. The histopathologic diagnosis of ECD is often challenging due to nonspecific inflammatory and fibrotic findings on histopathologic review of tissue specimens. Additionally, the association of ECD with unusual tissue tropism and an insidious onset often results in diagnostic errors and delays. Most patients with ECD require treatment, except for a minority of patients with minimally symptomatic single-organ disease. The first ECD consensus guidelines were published in 2014 on behalf of the physicians and researchers within the Erdheim-Chester Disease Global Alliance. With the recent molecular discoveries and the approval of the first targeted therapy (vemurafenib) for BRAF-V600-mutant ECD, there is a need for updated clinical practice guidelines to optimize the diagnosis and treatment of this disease. This document presents consensus recommendations that resulted from the International Medical Symposia on ECD in 2017 and 2019. Herein, we include the guidelines for the clinical, laboratory, histologic, and radiographic evaluation of ECD patients along with treatment recommendations based on our clinical experience and review of literature in the molecular era.
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Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/terapia , Ensaios Clínicos como Assunto , Doença de Erdheim-Chester/genética , Feminino , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/terapia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Terapia de Alvo Molecular , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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Linfadenopatia Imunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/patologia , Linfadenopatia Imunoblástica/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapiaRESUMO
Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation ("watch and wait") may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.
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Doença de Erdheim-Chester , Neoplasias Hematológicas , Histiocitose de Células de Langerhans , Histiocitose Sinusal , Adulto , Doença de Erdheim-Chester/tratamento farmacológico , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/patologia , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/tratamento farmacológico , Histiocitose Sinusal/patologia , Humanos , PrognósticoRESUMO
OBJECTIVES: Castleman disease (CD) is a heterogeneous group of disorders involving systemic inflammation and lymphoproliferation. Recently, clonal mutations have been identified in unicentric CD (UCD) and idiopathic multicentric CD (iMCD), suggesting a potential underlying neoplastic process. METHODS: Patients with UCD or iMCD with next generation sequencing (NGS) data on tissue DNA and/or circulating tumor DNA (ctDNA) were included. RESULTS: Five patients were included, 4 with iMCD and 1 with UCD. Four patients (80%) were women; median age was 40 years. Three of five patients (60%) had ≥1 clonal mutation detected on biopsy among the genes included in the panel. One patient with iMCD had a 14q32-1p35 rearrangement and a der(1)dup(1)(q42q21)del(1)(q42) (1q21 being IL-6R locus) on karyotype. This patient also had a NF1 K2459fs alteration on ctDNA (0.3%). Another patient with iMCD had a KDM5C Q836* mutation, and one patient with UCD had a TNS3-ALK fusion but no ALK expression by immunohistochemistry. CONCLUSIONS: We report 4 novel somatic alterations found in patients with UCD or iMCD. The 1q21 locus contains IL-6R, and duplication of this locus may increase IL-6 expression. These findings suggest that a clonal process may be responsible for the inflammatory phenotype in some patients with UCD and iMCD.
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Hiperplasia do Linfonodo Gigante/patologia , Mutação , Adulto , Hiperplasia do Linfonodo Gigante/genética , Aberrações Cromossômicas , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
Primary cutaneous anaplastic large-cell lymphoma and breast implant-associated ALCL (BIA-ALCL) are rare subtypes of anaplastic lymphoma kinase (ALK)-negative ALCLs originating from skin and breast implants, respectively. Herein, we report a unique case of cutaneous ALK-negative ALCL occurring in the skin of left medial breast from a patient with multiple rounds of bilateral breast implants and a history of breast carcinoma. The lymphoma cells are entirely confined to the lymphatic channels in the dermis, and the patient has no other areas of skin abnormality, no lymphadenopathy, peri-implant fluid accumulation, or masses from the bilateral capsules of implants. The differential diagnosis and its relationship with breast implants are further explored.
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Implantes de Mama/efeitos adversos , Neoplasias da Mama/cirurgia , Linfoma Anaplásico de Células Grandes/diagnóstico , Neoplasias Cutâneas/patologia , Idoso , Quinase do Linfoma Anaplásico/metabolismo , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/uso terapêutico , Biópsia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Diagnóstico Diferencial , Feminino , Humanos , Antígeno Ki-67/metabolismo , Vasos Linfáticos/patologia , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/ultraestrutura , Pele/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Rosai-Dorfman-Destombes (RDD) disease, is a rare proliferative and inflammatory disorder of non-Langerhans cell histiocytes. CASE PRESENTATION: We report a 35-year-old woman, who originally presented with recurrent episodes of lower extremity joint/bone pain and chronic nasal stuffiness and congestion. Her worsening nasal congestion was due to an obstructing nasal cavity lesion which was subsequently biopsied. Pathology was consistent with RDD. 18F-FDG PET images demonstrated intense uptake in the paranasal sinuses and a large pelvic lymph node. Focal osseous lesions with intense 18F-FDG uptake were also observed in the lower extremity, corresponding to areas of peri-articular pain. Rheumatologic work-up was consistent with palindromic rheumatism. She was diagnosed with immune-related disseminated RDD, presenting as palindromic rheumatism. CONCLUSIONS: This is the first case of RDD presenting as palindromic rheumatism. RDD should be considered as a possible but rare diagnosis in young patients with sinus-related symptoms and lymphadenopathy. The disease can on rare occasions be disseminated and can also present as immune-related RDD, such as in this patient.
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Artrite Reumatoide/etiologia , Histiocitose Sinusal/complicações , Doenças Nasais/complicações , Adulto , Tornozelo/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Histiocitose Sinusal/diagnóstico por imagem , Histiocitose Sinusal/patologia , Humanos , Joelho/diagnóstico por imagem , Linfadenopatia/diagnóstico por imagem , Doenças Nasais/diagnóstico por imagem , Doenças Nasais/patologia , Seios Paranasais/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Imagem Corporal Total/métodosRESUMO
INTRODUCTION: Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE) antibody that simultaneously binds CD19 on the surface of B-cells and CD3 on the surface of T-cells, resulting in tumor cell lysis. It is approved for the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and in patients with minimal residual disease after intensive induction chemotherapy. Relapse patterns after treatment with blinatumomab have not been well characterized. METHODS: We reviewed patients treated with blinatumomab with relapsed, refractory or minimal residual disease-positive B-ALL from 1 December 2014 to 31 December 2018 at a single academic medical center. Patient demographics, blast percentage prior to blinatumomab initiation, prior lines of therapy, blinatumomab treatment duration, sites of relapse, progression free survival, and overall survival were collected. RESULTS: A total of 20 patients were identified. Four (20%) patients developed extramedullary relapse following blinatumomab. The median time from treatment initiation to extramedullary relapse was 179 days (range 47-241). Sites of extramedullary relapse included the pancreas, adrenal gland, kidneys, liver, parotid gland, and brain. CONCLUSION: Extramedullary relapse occurs frequently following treatment of B-ALL with blinatumomab. Further studies aimed at preventing extramedullary relapse following blinatumomab treatment are warranted.
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Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Intervalo Livre de Progressão , Recidiva , Fatores Socioeconômicos , Análise de SobrevidaRESUMO
In arthropod community ecology, species richness studies tend to be prioritised over those investigating patterns of abundance. Consequently, the biotic and abiotic drivers of arboreal arthropod abundance are still relatively poorly known. In this cross-continental study, we employ a theoretical framework in order to examine patterns of covariance among herbivorous and predatory arthropod guilds. Leaf-chewing and leaf-mining herbivores, and predatory ants and spiders, were censused on > 1000 trees in nine 0.1 ha forest plots. After controlling for tree size and season, we found no negative pairwise correlations between guild abundances per plot, suggestive of weak signals of both inter-guild competition and top-down regulation of herbivores by predators. Inter-guild interaction strengths did not vary with mean annual temperature, thus opposing the hypothesis that biotic interactions intensify towards the equator. We find evidence for the bottom-up limitation of arthropod abundances via resources and abiotic factors, rather than for competition and predation.
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Artrópodes , Aranhas , Animais , Herbivoria , Comportamento Predatório , ÁrvoresRESUMO
RAS alterations are often found in difficult-to-treat malignancies and are considered "undruggable." To better understand the clinical correlates and coaltered genes of RAS alterations, we used targeted next-generation sequencing (NGS) to analyze 1,937 patients with diverse cancers. Overall, 20.9% of cancers (405/1,937) harbored RAS alterations. Most RAS-altered cases had genomic coalterations (95.3%, median: 3, range: 0-51), often involving genes implicated in oncogenic signals: PI3K pathway (31.4% of 405 cases), cell cycle (31.1%), tyrosine kinase families (21.5%) and MAPK signaling (18.3%). Patients with RAS-altered versus wild-type RAS malignancies had significantly worse overall survival (OS; p = 0.02 [multivariate]), with KRAS alterations, in particular, showing shorter survival. Moreover, coalterations in both RAS and PI3K signaling or cell-cycle-associated genes correlated with worse OS (p = 0.004 and p < 0.0001, respectively [multivariate]). Among RAS-altered patients, MEK inhibitors alone did not impact progression-free survival (PFS), while matched targeted therapy against non-MAPK pathway coalterations alone showed a trend toward longer PFS (vs. patients who received unmatched therapy) (HR: 0.79, 95% CI: 0.61-1.03, p = 0.07). Three of nine patients (33%) given tailored combination therapies targeting both MAPK and non-MAPK pathways achieved objective responses. In conclusion, RAS alterations correlated with poor survival across cancers. The majority of RAS alterations were accompanied by coalterations impacting other oncogenic pathways. MEK inhibitors alone were ineffective against RAS-altered cancers while matched targeted therapy against coalterations alone correlated with a trend toward improved PFS. A subset of the small number of patients given MEK inhibitors plus tailored non-MAPK-targeting agents showed responses, suggesting that customized combinations warrant further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Neoplasias/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas ras/genética , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , California/epidemiologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Estudos Observacionais como Assunto , Medicina de Precisão , Prognóstico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Proteínas ras/metabolismoRESUMO
BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. The BRAF inhibitor vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for patients with ECD harboring a BRAF V600E mutation. Successful treatment has also been reported with MEK-targeted therapies, likely because of the fact that BRAF mutant-negative patients harbor MEK pathway alterations. In our Rare Tumor Clinic, we noted that these patients have frequent drug-related toxicity, consistent with previous reports indicating the need to markedly lower doses of interferon-alpha when that agent is used in these patients. PATIENTS AND METHODS: We performed a review of ten patients with ECD seen at the Rare Tumor Clinic at University of California San Diego receiving 16 regimens of targeted BRAF, MEK, or combined therapies. RESULTS: The median age of the ten patients with ECD was 53 years (range, 29-77); seven were men. The median dose percentage (percent of FDA-approved dose) tolerated was 25% (range, 25%-50%). The most common clinically significant adverse effects resulting in dose adjustments of targeted therapies were rash, arthralgias, and uveitis. Renal toxicity and congestive heart failure were seen in one patient each. In spite of these issues, eight of ten patients (80%) achieved a partial remission on therapy. DISCUSSION: Patients with ECD appear to require substantially reduced doses of BRAF and MEK inhibitors but are responsive to these lower doses.
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Doença de Erdheim-Chester , Adulto , Idoso , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , VemurafenibRESUMO
Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti-interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.
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Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Ensaios Clínicos como Assunto , Estado Terminal/terapia , Gerenciamento Clínico , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
Assuntos
Linfoma Cutâneo de Células T/patologia , Micose Fungoide/diagnóstico , Neoplasias Cutâneas/patologia , Guias como Assunto , Humanos , Micose Fungoide/patologiaRESUMO
Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.