RESUMO
ABSTRACT: Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.
Assuntos
Infecções por Vírus Epstein-Barr , Infecções por HIV , Linfoma Plasmablástico , Humanos , Pessoa de Meia-Idade , Linfoma Plasmablástico/patologia , Estudos Retrospectivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , PrognósticoRESUMO
We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.
Assuntos
Citopenia , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Neoplasias , Humanos , Síndromes Mielodisplásicas/genética , Mutação , Linfócitos T/patologia , Transtornos Mieloproliferativos/genéticaRESUMO
For a disease initially described in 1958 as a leukaemic reticulo-endotheliosis associated with poor outcomes, we have come a long way in our understanding of Hairy cell leukaemia. The vast majority of patients diagnosed with this rare, often diagnostically challenging, leukaemia can now expect a lifespan that is similar to the general population. This article covers some of the highlights from the last 6 decades that have led to our current understanding of this fascinating leukaemia - from elucidation of its B-cell origin to discovery of the almost universal occurrence of the BRAF V600E mutation; from the initial successes reported with splenectomy to the more recent development of targeted therapies such as Vemurafenib and Moxetumomab Pasudotox. It also pays tribute to some of the outstanding research in this field focusing particularly on the significant contributions made by the clinical and scientific community in the UK.
Assuntos
Suscetibilidade a Doenças , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/etiologia , Proteínas Proto-Oncogênicas B-raf/genética , Terapia Combinada , Gerenciamento Clínico , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Leucemia de Células Pilosas/metabolismo , Leucemia de Células Pilosas/terapia , Proteínas Proto-Oncogênicas B-raf/metabolismoRESUMO
From the outset of the COVID-19 pandemic, patients and healthcare professionals have been concerned that a history of haematological malignancy will lead to an increased risk of severe COVID-19. This led to the UK government advising patients with blood cancers to shield, massive re-organisation of NHS haematology and cancer services, and changes in treatment plans for thousands of patients. Given the unknown effects that relaxation of social-distancing measures will have on the infection rate, we review the evidence to date to see whether a history of haematological malignancy is associated with increased risk of COVID-19. Multivariable analysis of large population studies, taking other known risk factors into account, do indicate that patients with haematological malignancy, especially those diagnosed recently, are at increased risk of death from COVID-19 compared to the general population. The evidence that this risk is higher than for those with solid malignancies is conflicting. There is suggestive evidence from smaller cohort studies that those with myeloid malignancy may be at increased risk within the blood cancer population, but this needs to be confirmed on larger studies. Ongoing large collaborative efforts are required to gain further evidence regarding specific risk factors for severe complications of COVID-19.
Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Neoplasias Hematológicas/complicações , Pneumonia Viral/complicações , COVID-19 , Infecções por Coronavirus/epidemiologia , Medicina Baseada em Evidências/métodos , Neoplasias Hematológicas/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Prevalência , Fatores de Risco , SARS-CoV-2RESUMO
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a new provisional category in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms, and its incidence is rising owing to increasing recognition of this complication of breast implant insertion. At a median of 10 years after implant insertion, the typical presenting features are sudden-onset breast swelling secondary to peri-implant effusion and less frequently mass-forming disease. Histologic features comprise pleomorphic cells expressing CD30 and negative anaplastic lymphoma kinase (ALK) receptor, similar to systemic and cutaneous ALK-negative anaplastic large cell lymphoma (ALCL). The effusion-only subtype is generally indolent and curable with surgery, unlike the more aggressive mass-forming disease, for which systemic therapy is advocated. High clinical suspicion and pertinent use of radiologic and pathology modalities are essential for timely and accurate diagnosis of BIA-ALCL. Contemporary imaging techniques including US, mammography, breast MRI, CT, and PET/CT are routinely used in breast disease and lymphomas; however, the unique behavior of BIA-ALCL presents significant diagnostic and radiologic interpretative challenges, with numerous nuanced imaging features being pertinent, and current lymphoma staging and response guidelines are not easily applicable to BIA-ALCL. The authors evaluate available evidence in this evolving field; detail key indications, strengths, and limitations of the panoply of radiologic techniques for BIA-ALCL; and propose multiparametric imaging paradigms for management of the peri-implant effusion and mass-forming or advanced disease subtypes, with the goal of accurate optimal patient care. The authors also predict a future model of multimodal assessment using novel imaging and molecular techniques and define key research directions. ©RSNA, 2020.
Assuntos
Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/etiologia , Imagem Multimodal , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/terapiaAssuntos
Receptores de Antígenos de Linfócitos T alfa-beta , Linfócitos T , Humanos , Citometria de Fluxo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Receptores de Antígenos de Linfócitos T/genética , Células ClonaisAssuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Sistema Cardiovascular/efeitos dos fármacos , Inibidores de Proteínas Quinases/efeitos adversos , Animais , Doenças Cardiovasculares/terapia , Tomada de Decisão Clínica , Diagnóstico Diferencial , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de RiscoAssuntos
Neoplasias Encefálicas/diagnóstico por imagem , Colina/análogos & derivados , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Encefálicas/metabolismo , Colina/administração & dosagem , Feminino , Humanos , Linfoma/metabolismo , Pessoa de Meia-IdadeAssuntos
Neoplasias Encefálicas , Fibrina/metabolismo , Hematoma Subdural , Linfoma Difuso de Grandes Células B , Idoso , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Hematoma Subdural/complicações , Hematoma Subdural/metabolismo , Hematoma Subdural/patologia , Humanos , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , MasculinoAssuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Neuroimagem/métodos , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Colina/análogos & derivados , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma não Hodgkin/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos RadiofarmacêuticosAssuntos
Doença de Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Brentuximab Vedotin/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab/administração & dosagem , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
Phosphoinositide-3 kinase (PI3K) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis, but early-phase studies of the PI3K p110δ inhibitor GS-1101 have reported inferior responses in MCL compared with other non-Hodgkin lymphomas. Because the relative importance of the class IA PI3K isoforms p110α, p110ß, and p110δ in MCL is not clear, we studied expression of these isoforms and assessed their contribution to PI3K signaling in this disease. We found that although p110δ was highly expressed in MCL, p110α showed wide variation and expression increased significantly with relapse. Loss of phosphatase and tensin homolog expression was found in 16% (22/138) of cases, whereas PIK3CA and PIK3R1 mutations were absent. Although p110δ inhibition was sufficient to block B-cell receptor-mediated PI3K activation, combined p110α and p110δ inhibition was necessary to abolish constitutive PI3K activation. In addition, GDC-0941, a predominantly p110α/δ inhibitor, was significantly more active compared with GS-1101 against MCL cell lines and primary samples. We found that a high PIK3CA/PIK3CD ratio identified a subset of primary MCLs resistant to GS-1101 and this ratio increased significantly with relapse. These findings support the use of dual p110α/p110δ inhibitors in MCL and suggest a role for p110α in disease progression.
Assuntos
Linfoma de Célula do Manto/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/fisiologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Purinas/administração & dosagem , Purinas/farmacologia , Purinas/uso terapêutico , Quinazolinonas/administração & dosagem , Quinazolinonas/farmacologia , Quinazolinonas/uso terapêutico , Recidiva , Transdução de Sinais/fisiologia , Especificidade por Substrato , Resultado do TratamentoAssuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Sulfonamidas/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Retratamento , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Treatment with CHOP-based chemotherapy with consolidative radiotherapy (CRT) for primary mediastinal B cell lymphoma (PMBCL) has been the standard approach in the pre-rituximab era. Overtreatment with CRT for patients who may have already been cured by primary immunochemotherapy in the rituximab era is a significant concern due to the long-term toxicity associated with radiotherapy. Positron emission tomography (PET) may help to identify patients who may not benefit from further CRT. METHODS: We conducted a retrospective review of patients treated at the Royal Marsden Hospital between 2003 and 2020 for PMBCL to assess CRT use and survival outcomes. RESULTS: Forty-three patients were identified, with 95% of the patients receiving R-CHOP. CRT was given in 5 patients. Five-year event-free survival was 79% (95% confidence interval: 64%-89%) and 5-year overall survival was 88% (95% confidence interval: 73%-95%). Seven of 9 patients with DS4 did not receive CRT and instead monitored with serial PET scans. None of these 7 patients relapsed in the mediastinum. CONCLUSION: CRT may be omitted in patients with a negative end of treatment PET scans; however, careful observation may also obviate the need for CRT in PET positive patients.