RESUMO
There is a large therapeutic gap in the treatment of sickle cell disease (SCD). Recent studies demonstrated the presence of pathophysiological and microbial changes in the intestine of patients with SCD. The intestinal microbes have also been found to regulate neutrophil ageing and possible basal activation of circulating neutrophils. Both aged and activated neutrophils are pivotal for the pathogenesis of vaso-occlusive crisis in SCD. In this paper, we will provide an overview of the intestinal pathophysiological and microbial changes in SCD. Based on these changes, we will propose therapeutic approaches that could be investigated for treating SCD.
Assuntos
Anemia Falciforme/microbiologia , Microbioma Gastrointestinal , Doenças Vasculares/microbiologia , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Senescência Celular , Humanos , Neutrófilos/metabolismo , Doenças Vasculares/sangue , Doenças Vasculares/etiologia , Doenças Vasculares/terapiaAssuntos
Infecções Bacterianas/diagnóstico , Febre/diagnóstico , Mieloma Múltiplo/terapia , Infecções Oportunistas/diagnóstico , Pró-Calcitonina/sangue , Idoso , Infecções Bacterianas/sangue , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Diagnóstico Diferencial , Feminino , Febre/sangue , Febre/imunologia , Febre/microbiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/microbiologia , Infecções Oportunistas/sangue , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Estudos Retrospectivos , Transplante AutólogoAssuntos
Febre/etiologia , Recursos em Saúde/estatística & dados numéricos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adulto , Idoso , Infecções Bacterianas/complicações , Citocinas/fisiologia , Suscetibilidade a Doenças , Feminino , Recursos em Saúde/economia , Neoplasias Hematológicas/terapia , Mobilização de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/economia , Síndrome , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo/efeitos adversos , Viroses/complicações , Adulto JovemAssuntos
Actinomicose/fisiopatologia , Anemia Hemolítica Autoimune/fisiopatologia , Febre/tratamento farmacológico , Febre/fisiopatologia , Osteomielite/fisiopatologia , Prednisona/uso terapêutico , Trombocitopenia/fisiopatologia , Idoso , Feminino , Febre/diagnóstico , Humanos , Unidades de Terapia Intensiva , Resultado do TratamentoRESUMO
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell hematologic neoplasm with a very poor prognosis and limited treatment options to date. Single-agent alemtuzumab remains the first line of therapy for the treatment-naive and relapsed/refractory patients. Prospective clinical trials are difficult to conduct given that these patients have a short life expectancy after the initial diagnosis. As a result, researchers are implementing the use of targeted therapies in vitro and ex vivo followed by in vivo trials on a small subset of patients which are reviewed here. Newer approaches in the treatment of T-PLL are developing based on recognizing the cytogenetic phenotype of each patient and targeting the identified defective genes that are usually involved in the cell cycle regulation such as protooncogenes, tumor suppressors, and deoxyribonucleic acid (DNA) repair genes. These could potentially redirect the management in the near future and improve the overall survival (OS) and the progression-free survival (PFS) for these patients.
RESUMO
Renal cell carcinoma (RCC) is a common cancer that affects a significant number of patients every year around the world. The presence of sarcomatoid features in these tumors is considered a poor prognostic feature. Patients with RCC with sarcomatoid features had significantly worse outcomes when treated with sunitinib, the previous first-line standard of care therapy when compared to patients without such features. Multiple immune checkpoint inhibitors have recently been approved for the treatment of RCC. In this article, we review the literature available on the outcomes of patients with sarcomatoid RCC treated with immune checkpoint inhibitors.
RESUMO
Sickle cell disease (SCD) is one of the most common hereditary hemoglobinopathies worldwide. It is a multisystem disease that causes considerable patient morbidity. Despite advances in medical treatment, cardiopulmonary complications remain the most common cause of death in individuals with SCD. A growing body of evidence has shown that SCD results in a spectrum of cardiovascular complications through a variety of mechanisms, including chronic hemolysis, local tissue hypoxia, increased oxidative stress, and autonomic instability. Herein, we will examine the pathophysiology of sickle cell vasculopathy and discuss the spectrum of cardiovascular sequelae of the disease, while highlighting the impact of SCD on the cardiovascular health of the patients.
Assuntos
Anemia Falciforme/complicações , Doenças Cardiovasculares/etiologia , Humanos , Hipóxia , Estresse Oxidativo , Doenças Vasculares/etiologiaRESUMO
B cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) frequently express CD19, CD20 and CD22 on the cell surfaces. Immunotherapeutic agents including antibodies and chimeric antigen receptor T cells are widely studied in clinical trials. Several antibody-drug conjugates (ADC) have been approved for clinical use (gemtuzumab ozogamicin in acute myeloid leukemia and brentuximab vedotin in Hodgkin lymphoma as well as CD30+ anaplastic large cell lymphoma). Inotuzumab ozogamicin (INO), a CD22 antibody conjugated with calicheamicin is one of the newest ADCs. INO has been approved for treatment of relapsed /refractory B cell precursor ALL. Multiple ongoing trials are evaluating its role in the relapsed /refractory B cell NHL. This review summarized recent development in INO applications for ALL and NHL.
RESUMO
Although relapse of acute leukemia is common, a change of immunophenotype at relapse only occurs rarely. Some of these cases have been labeled "lineage switch". In most cases, B-cell lymphoblastic leukemia/lymphoma (B-ALL) relapses as acute myeloid leukemia (AML). We report a rare case of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) relapsing as AML and then returning as T-ALL again in a patient who began her therapy during the third trimester of pregnancy. The patient retained the same cytogenetic and next generation molecular findings in both leukemias. This case provides further evidence of the plasticity of the leukemic stem cell.
RESUMO
Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach. E7107, a spliceosome inhibitor, has been shown to differentially inhibit splicing more in SRSF2-mutant cells leading to decreased leukemia burden in mice. H3B-8800 is a small molecule modulator of spliceosome complex and has been shown to lower leukemia burden in SRSF2-P95H mutant mice. This review focuses on the incidence of mutant SRSF2 across various MMOS as well as recent clinical development of spliceosome inhibitors.
RESUMO
Thrombotic thrombocytopenic purpura (TTP) is a part of a spectrum of thrombotic microangiopathy syndromes which are mainly characterized by platelet aggregation causing microangiopathic hemolytic anemia, thrombocytopenia and microvascular occlusion. In literature, very few cases expressing a direct association between pre-existing Grave's disease and TTP have been described. A 37-year-old African-American woman with past medical history of Grave's disease and polysubstance abuse who presented with complaints of dyspnoea at rest and chest pain was diagnosed to have TTP on further evaluation. Patient also showed severely elevated thyroid hormones and suppressed thyroid stimulating hormone levels indicating severe thyrotoxicosis. Initiation of prompt management of TTP and thyrotoxicosis led to a favorable patient outcome. In conclusion, patients presenting with thyrotoxicosis, thrombocytopenia and microangioapthic hemolytic anemia without an alternative cause should be treated and screened for TTP due to the high fatality associated with untreated or untimely detection of this disease.