RESUMO
INTRODUÇÃO: O mieloma múltiplo é uma neoplasia de plasmócitos com incidência anual no Brasil de 1,24 casos a cada 100.000 habitantes. Apesar de avanços no tratamento da doença, o mieloma múltiplo é considerado incurável e o objetivo da terapia é induzir a remissão e prolongar a sobrevida do paciente preservando sua qualidade de vida. Um dos principais tratamentos é o TCTH. No entanto, uma parcela significativa dos pacientes não é elegível ao TCTH podendo ser apenas submetida a medicamentos. A lenalidomida é um imunomodulador que pode ser utilizado na terapia de indução e manutenção nesses pacientes. Desta forma, o objetivo deste Relatório é comparar eficácia, segurança, custo-efetividade e impacto orçamentário da lenalidomida em relação à talidomida, imunomodulador disponível no SUS, em pacientes com mieloma múltiplo inelegíveis ao TCTH. TECNOLOGIA: Lenalidomida. PERGUNTA: A lenalidomida é mais eficaz, segura e custo-efetiva em esquemas com dois ou três medicamentos comparada à talidomida em esquemas terapêuticos com dois ou três medicamentos para o t
Assuntos
Humanos , Talidomida/uso terapêutico , Transplante de Células/efeitos adversos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economiaRESUMO
BACKGROUND: We have entered a new era of cancer therapy, with a number of immune-based therapies already used clinically as a standard of care. Adoptive cellular immunotherapy using T cells genetically modified with chimeric antigen receptors (CAR-T cells) represents a novel therapeutic approach. CAR-T cells have produced clinical responses in B-cell malignancies that are otherwise refractory to conventional therapies. Two CAR-T cell therapies obtained regulatory approval in 2017, with many more of these therapies under clinical development. CONTENT: This review focuses on the current state of adoptive cellular immunotherapy, specifically CAR-T cells, in the clinic and how this therapy differs from traditional small molecule and biologic therapies. Areas in which the clinical laboratory is affected by these novel therapies are discussed. Opportunities for the clinical laboratory to help guide these therapies are also highlighted. SUMMARY: The clinical laboratory will play an integral role in the care of patients undergoing adoptive cellular therapy with engineered T cells. There are many ways that this new therapeutic approach affects the clinical laboratory, and the clinical laboratory will likely play a critical role in managing patients that are treated with CAR-T cell therapy.
Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Transplante de Células/efeitos adversos , Transplante de Células/métodos , Humanos , Imunoterapia Adotiva/efeitos adversos , Neoplasias/imunologia , Receptores de Antígenos Quiméricos/genéticaRESUMO
Leukotriene B4 (LTB4), a proinflammatory mediator produced by the enzyme 5-lipoxygenase (5-LO), is associated with the development of many inflammatory diseases. In this study, we evaluated the participation of the 5-LO/LTB4 axis in graft-versus-host disease (GVHD) pathogenesis by transplanting 5-LO-deficient leukocytes and investigated the effect of pharmacologic 5-LO inhibition by zileuton and LTB4 inhibition by CP-105,696. Mice that received allogeneic transplant showed an increase in nuclear 5-LO expression in splenocytes, indicating enzyme activation after GVHD. Mice receiving 5-LO-deficient cell transplant or zileuton treatment had prolonged survival, reduced GVHD clinical scores, reduced intestinal and liver injury, and decreased levels of serum and hepatic LTB4 These results were associated with inhibition of leukocyte recruitment and decreased production of cytokines and chemokines. Treatment with CP-105,696 achieved similar effects. The chimerism or the beneficial graft-versus-leukemia response remained unaffected. Our data provide evidence that the 5-LO/LTB4 axis orchestrates GVHD development and suggest it could be a target for the development of novel therapeutic strategies for GVHD treatment.
Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Transplante de Células/métodos , Doença Enxerto-Hospedeiro/metabolismo , Leucotrieno B4/metabolismo , Animais , Araquidonato 5-Lipoxigenase/genética , Benzopiranos/farmacologia , Ácidos Carboxílicos/farmacologia , Transplante de Células/efeitos adversos , Quimiocinas/metabolismo , Citocinas/metabolismo , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Hidroxiureia/análogos & derivados , Hidroxiureia/farmacologia , Leucócitos/citologia , Leucócitos/enzimologia , Leucócitos/metabolismo , Antagonistas de Leucotrienos/farmacologia , Leucotrieno B4/antagonistas & inibidores , Inibidores de Lipoxigenase/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia Confocal , Transplante HomólogoRESUMO
BACKGROUND: This is a preliminary report on successful results obtained during treatment of two patients with chronic spinal cord injury. The therapeutic approach was based on the generation of controlled inflammatory activity at the injury site that induced a microenvironment for the subsequent administration of autologous, BM-driven transdifferentiated neural stem cells (NSC). METHODS: BM mesenchymal stem cells (MSC) were cocultured with the patient's autoimmune T (AT) cells to be transdifferentiated into NSC. Forty-eight hours prior to NSC implant, patients received an i.v. infusion of 5 x 10(8) to 1 x 10(9) AT cells. NSC were infused via a feeding artery of the lesion site. Safety evaluations were performed everyday, from the day of the first infusion until 96 h after the second infusion. After treatment, patients started a Vojta and Bobath neurorehabilitation program. RESULTS: At present two patients have been treated. Patient 1 was a 19-year-old man who presented paraplegia at the eight thoracic vertebra (T8) with his sensitive level corresponding to his sixth thoracic metamere (T6). He received two AT-NSC treatments and neurorehabilitation for 6 months. At present his motor level corresponds to his first sacral metamere (S1) and his sensitive level to the fourth sacral metamere (S4). Patient 2 was a 21-year-old woman who had a lesion that extended from her third to her fifth cervical vertebrae (C3-C5). Prior to her first therapeutic cycle she had severe quadriplegia and her sensitive level corresponded to her second cervical metamere (C2). After 3 months of treatment her motor and sensitive levels reached her first and second thoracic metameres (T1-T2). No adverse events were detected in either patient. DISCUSSION: The preliminary results lead us to think that this minimally invasive approach, which has minor adverse events, is effective for the repair of chronic spinal cord lesions.
Assuntos
Transplante de Células/métodos , Regeneração Nervosa , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco/métodos , Linfócitos T/transplante , Adulto , Esclerose Lateral Amiotrófica/imunologia , Antígenos CD/análise , Complexo CD3/análise , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Separação Celular/métodos , Transplante de Células/efeitos adversos , Técnicas de Cocultura , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/citologia , Proteínas do Tecido Nervoso/imunologia , Neurônios/citologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/fisiopatologia , Transplante de Células-Tronco/efeitos adversos , Células-Tronco/citologia , Linfócitos T/química , Linfócitos T/imunologia , Resultado do TratamentoRESUMO
Over three decades of research in experimental animals and several clinical trials have brought us to the threshold of hepatocyte transplantation for the treatment of acute and chronic liver failure, and inherited metabolic disorders. However, more extensive clinical studies and routine clinical application are hampered by the shortage of good quality of donor cells. To overcome these hurdles, current research has focused on the search for alternatives to adult primary hepatocytes, such as liver cell progenitors, fetal hepatoblasts, embryonic, bone marrow or umbilical cord blood stem cells and conditionally immortalized hepatocytes. Cross-species hepatocyte transplantation is also being explored. It is hoped that ongoing research will permit the application of hepatocyte transplantation to the treatment of a wide array of liver diseases.