RESUMO
Hematological malignancies represent defying clinical conditions, with high levels of morbidity and mortality, particularly considering patients who manifest multiple refractory diseases. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a potential treatment option for relapsed/refractory B cell malignancies, which have motivated the Food and Drug Administration approval of a series of products based on this technique. The objective of this systematic review was to assess the efficacy and safety of CAR-T cell therapy for patients with hematological malignancies. A comprehensive literature search was conducted in the electronic databases (CENTRAL, Embase, LILACS, and MEDLINE), clinical trials register platforms (Clinicaltrials.gov and WHO-ICTRP), and grey literature (OpenGrey). The Cochrane Handbook for Reviews of Interventions was used for developing the review and the PRISMA Statement for manuscript reporting. The protocol was prospectively published in PROSPERO database (CRD42020181047). After the selection process, seven RCTs were included, three of which with available outcome results. The available results are from studies assessing axicabtagene, lisocabtagene, and tisagenlecleucel for patients with B cell lymphoma, and the certainty of evidence ranged from very low to low for survival and progression-related outcome and for safety outcomes. Additionally, four randomized controlled trials comparing CAR-T cell therapy to the standard treatment for various types of relapsed/refractory B cell non-Hodgkin lymphomas and multiple myeloma included in this systematic review still did not have available outcome data. The results of this review may be used to guide clinical practice but evidence concerning the safety and efficacy of CAR-T Cell therapy for hematological malignancies is still immature to recommend its application outside of clinical trials or compassionate use context for advanced and terminal cases. It is expected the results of the referred comparative studies will provide further elements to subsidize the broader application of this immunotherapy.
Assuntos
Neoplasias Hematológicas , Linfoma de Células B , Receptores de Antígenos Quiméricos , Humanos , Recidiva Local de Neoplasia , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/etiologia , Linfoma de Células B/terapia , Terapia Baseada em Transplante de Células e TecidosRESUMO
At the time of writing, five anti-CD19 CAR T-cell products are approved by the U.S. Food and Drug Administration for seven different indications in lymphoid malignancies, including B-cell non-Hodgkin lymphoma, pediatric B-cell acute lymphoblastic leukemia, and multiple myeloma. CAR T cells for chronic lymphocytic leukemia, acute myeloid leukemia, and less common malignancies such as T-cell lymphomas and Hodgkin lymphoma are being tested in early-phase clinical trials worldwide. The purpose of this overview is to describe the current landscape of CAR T cells in hematologic malignancies, outline their outcomes and toxicities, and explain the outstanding questions that remain to be addressed.
Assuntos
Imunoterapia Adotiva , Leucemia Linfocítica Crônica de Células B , Linfoma de Células B , Antígenos CD19 , Humanos , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma de Células B/terapia , Receptores de Antígenos de Linfócitos TRESUMO
Immunotherapy using T cells modified with chimeric antigen receptor (CAR) has been proven effective in the treatment of leukemia and lymphomas resistant to chemotherapy. Recent clinical studies have shown excellent responses of CAR-T cells in a variety of B cell tumors. However, it is important to validate in vitro activity of these cells, though different sorts of assays, which are capable of measuring the cytotoxic potential of these cells. In this chapter, it will be pointed two methods to evaluate CAR-T cell killing potential against B cell malignancy cell lines.
Assuntos
Técnicas de Cocultura , Citotoxicidade Imunológica , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Biomarcadores , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Humanos , Imunoterapia Adotiva/métodos , Leucemia de Células B/genética , Leucemia de Células B/imunologia , Leucemia de Células B/patologia , Leucemia de Células B/terapia , Linfoma de Células B/genética , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genéticaRESUMO
B-cell lymphoblastic lymphoma (B-LBL) is a malignant neoplasm of immature B cells that accounts for only 10% of all cases of lymphoblastic lymphoma. Most commonly, B-LBL presents as bony lesions, but in rare cases, the disease manifests cutaneously. We present a case of simultaneous cutaneous and systemic presentation of B-LBL in an otherwise healthy 28-year-old man in which the lymphoblastic infiltrate stained positive for CD79a, Tdt, CD10, and CD20. A diagnosis of cutaneous B-LBL was made, and systemic work-up revealed widespread involvement of the skin, bone, and lymph nodes. Review of all currently described cases of cutaneous B-LBL with or without systemic involvement revealed that the most frequently positive tumor markers were CD79a (92.3%), Tdt (90.6%), and CD10 (83.3%). Systemic involvement of B-LBL was found in nearly half of all cases with cutaneous presentation.
Assuntos
Leucemia Linfoide/diagnóstico , Linfoma de Células B/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Antígenos CD20/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biópsia , Antígenos CD79/análise , DNA Nucleotidilexotransferase/antagonistas & inibidores , Fracionamento da Dose de Radiação , Transplante de Células-Tronco Hematopoéticas , Humanos , Imuno-Histoquímica , Leucemia Linfoide/imunologia , Leucemia Linfoide/patologia , Leucemia Linfoide/terapia , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Masculino , Neprilisina/análise , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Resultado do TratamentoRESUMO
TITLE: Linfoma B intravascular hipotalamico en una paciente inmunocompetente.
Assuntos
Hipotálamo/irrigação sanguínea , Linfoma de Células B/patologia , Neoplasias Vasculares/patologia , Idoso , Terapia Combinada , Confusão/etiologia , Irradiação Craniana , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Hipotireoidismo/etiologia , Imunocompetência , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/terapia , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Transtornos do Sono do Ritmo Circadiano/etiologia , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/terapia , Vasopressinas/deficiência , Redução de PesoRESUMO
OBJECTIVE: Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. An official report published by the Mexican National Center for the Control and Prevention of Cancer in the Pediatric and Adolescent Populations, reported a lymphoma OS of 71% (including all Hodgkin and NHL). The Mexican Association of Pediatric Oncology and Hematology conducted a retrospective study to analyze the clinical characteristics and outcomes of children with diagnosis of B-NHL in Mexico, in order to perceive the main areas of improvement in the health care. METHODS: From 1 January 2000 to 31 December 2016, 166 pediatric patients were diagnosed with B-cell NHL at the participant institutions. RESULTS: According to histology the outcomes were 5-year EFS 63%, for BL/BLL, and 80% DLBCL, (P = .051), 5-year PFS 81%, for BL/BLL, and 91% for DLBCL, (P = .126), and 5-year OS 71%, for BL/BLL, and 83% for DLBCL, (P = .095). DISCUSSION: Overall, 18 patients died due to acute treatment toxicity, resulting in a cumulative incidence of toxic death of 10.84% and an early death rate of 7.23%, defined as <30 days after initial treatment. In conclusion, there is an urgent need to establish an academic collaboration to create strategies to improve pediatric cancer care according to our resources, especially in diseases with expected excellent prognosis as B-NHL. These strategies must include comprehensive supportive care, early referral, and the creation of easy communication between pediatric and adults centers as well as late-effects clinics.
Assuntos
Linfoma de Células B/diagnóstico , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Encaminhamento e Consulta , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.
Assuntos
Vírus da Hepatite B , Linfoma de Células B/patologia , Linfoma de Células B/virologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/virologia , Adulto , Doença Crônica , Evolução Fatal , Feminino , Humanos , Linfoma de Células B/terapia , Pessoa de Meia-Idade , Neoplasias Esplênicas/terapia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
ANTECEDENTES: El linfoma no Hodgkin durante el embarazo es una entidad rara, el tipo difuso de células grandes es aún menos frecuente y se caracteriza por una alta tasa de progresión tumoral con poca expresión clínica. Su diagnóstico y tratamiento representan un reto clínico debido a la baja incidencia de la enfermedad y a las posibles repercusiones fetales a causa del tratamiento. CASO CLÍNICO: Gestante secundípara de 31 años que ingresa por cuadro de dolor abdominal y cifras elevadas de lactato deshidrogenasa. Durante la gestación precisa varios ingresos por pancreatitis aguda de repetición y cuadro de colestasis intrahepática. Tras el parto evoluciona tórpidamente con aparición de edema en esclavina en cuello y miembros superiores, siendo diagnosticada de gran masa torácica cuya biopsia es informada como Linfoma No Hodgkin tipo B difuso de células grandes primario mediastinal. Se administran dos ciclos de tratamiento quimioterápico tras lo cual remite completamente la enfermedad. Se induce el parto con prostaglandinas intravaginal, con recién nacido de 3350 gramos y APGAR 8/10. Tras un año la paciente permanece en remisión completa.
BACKGROUND: During pregnancy, Non-Hodgkin's lymphoma is a rare entity; the diffuse large cell lymphoma is still less common, and it has a high rate of tumor progression with a little clinical expression. Diagnosis and treatment is a huge challenge due to the low incidence of the condition and to the possible fetal effects because of the treatment. CLINICAL CASE: A 31-year-old woman -in her second delivery- was admitted with abdominal pain and elevated lactate dehydrogenase levels. During pregnancy, she was required several admissions reporting repeated acute pancreatitis and intrahepatic cholestasis. After delivery, it evolves into facial and upper extremity oedema, diagnosed with a large chest mass, resulting in the diagnosis of primary mediastinal large B-cell lymphoma through the biopsy. The disease goes into remission completely after two cycles of chemotherapy treatments are given. Labor is induced with intravaginal prostaglandins, with a newborn of 3350 g and Apgar 8/10. After a year, the patient remains in complete remission.
Assuntos
Humanos , Feminino , Adulto , Pancreatite/etiologia , Complicações Neoplásicas na Gravidez , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Biópsia , Linfoma não Hodgkin , Colestase Intra-Hepática , Linfoma de Células B/terapia , Trabalho de Parto Induzido , L-Lactato DesidrogenaseRESUMO
ABSTRACT CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.
RESUMO CONTEXTO: Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, é uma doença rara, representando menos do que 1% de todos os linfomas não Hodgkin. Essa entidade é caracterizada por envolvimento de sinusoides da medula óssea e sangue periférico. A maioria dos casos está em estádio avançado ao diagnóstico. Sua patogênese ainda é pouco compreendida. RELATOS DE CASOS: Reportamos dois pacientes com vírus da hepatite B (HBV) crônica não replicante que desenvolveram linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos. Ambos estavam em estádio IV ao diagnóstico e evoluíram com doença agressiva. Ambos alcançaram resposta completa com a quimioterapia, porém um deles evoluiu a óbito por intercorrências infecciosas durante o transplante de medula óssea e o outro optou por não realizar o transplante e encontra-se sem evidência de doença até os dias atuais (três anos após tratamento). Alguns estudos demonstraram a possível associação entre linfomas não Hodgkin B e HBV. Entretanto, o mecanismo pelo qual esse vírus oncogênico interage com linfoma não Hodgkin B ainda é pouco compreendido. HBV é linfotrópico e pode se inserir no genoma do receptor, causando superexpressão de oncogenes e downregulation de genes supressores tumorais. Portanto, o estímulo crônico pelo HBV pode aumentar a proliferação de células B, promovendo expansão monoclonal dessas células, resultando em malignidade. CONCLUSÃO: HBV pode estar implicado na patogênese desse linfoma, entretanto, uma associação direta entre essas duas entidades não pôde ser provada no presente estudo e investigações adicionais são necessárias.