Assuntos
Anafilaxia/induzido quimicamente , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/análise , Imunoconjugados/efeitos adversos , Choque/induzido quimicamente , Adulto , Anafilaxia/imunologia , Anticorpos Monoclonais/imunologia , Brentuximab Vedotin , Dessensibilização Imunológica/métodos , Humanos , Imunoconjugados/imunologia , Masculino , Choque/imunologiaRESUMO
BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Brentuximab Vedotin , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/terapia , Humanos , Imunoconjugados/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nivolumabe , Estudos Retrospectivos , Transplante de Células-Tronco , Adulto JovemRESUMO
OBJECTIVES: Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS: We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS: The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION: A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.
Assuntos
Micose Fungoide/tratamento farmacológico , Fotoferese , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Interferons/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Terapia PUVA , Indução de Remissão , Estudos Retrospectivos , Análise de SobrevidaRESUMO
OBJECTIVE: The resistance of blood to flow is called plasma viscosity. Increased blood viscosity has been described in patients with coronary and peripheral arterial disease. In this study, we evaluated the influence of clinical and laboratory findings on plasma viscosity in renal transplant recipients. METHODS: Eighty-one kidney transplant recipients (37.8 ± 11.3 years old, 50.38 ± 16.8 months post-transplantation period, 27 female) with normal graft functions were enrolled. The biochemical and clinical parameters in the 1st year after transplantation were retrospectively recorded, and graft function was evaluated by means of the yearly decline in eGFR. Plasma viscosity was measured and searched for the association with cross-sectionally analyzed cardiovascular parameters including body composition analyses, ambulatory blood pressure monitoring (ABPM) data, and pulse-wave velocity. RESULTS: Patients were divided into 2 groups according to the median value of serum viscosity. Patients with high viscosity had higher serum low-density lipoprotein (P = .042) and C-reactive protein (P = .046) levels than lower viscosity group. In ABPM, daytime (P = .047) and office systolic (P = .046) blood pressure levels and left ventricular mass index (LVMI; P = .012) were significantly higher in patients with hyperviscosity. Patients with high viscosity had higher hip circumference (P = .038) and fat mass (P = .048). Estimated glomerular filtration rate decline was significantly higher in high-viscosity patients than in patients with low viscosity levels (12.9% vs 17.2%; P = .001) at 2 years' follow-up. CONCLUSIONS: We suggest that the hyperviscous state of the renal transplant recipients may arise from the inflammatory state, hypertension, and increased fat mass and increased LVMI. Hyperviscosity is also closely related to renal allograft dysfunction.
Assuntos
Viscosidade Sanguínea , Função Retardada do Enxerto/sangue , Transplante de Rim/efeitos adversos , Transplantados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemAssuntos
Aeromonas hydrophila , Fasciite Necrosante/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Dermatoses da Perna/diagnóstico , Infecções Oportunistas/diagnóstico , Fasciite Necrosante/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Humanos , Hospedeiro Imunocomprometido , Dermatoses da Perna/imunologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/imunologia , Coxa da PernaRESUMO
Angiogenesis plays a significant role in a variety of malignant hematologic diseases, and it is recognized that it has prognostic value. However, the cellular mechanisms by which malignant hematologic cells induce angiogenesis are not well understood. In order to investigate the role of cells from B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) in angiogenesis on human bone marrow endothelial cells (HBMEC), we analyzed the impact of factors secreted by B-CLL cells and by MM cells on HBMEC capillary tube formation on matrigel. It was found that, in addition to the secretion of angiogenic factors VEGF and b-FGF by B-CLL and MM cells, MM cells (but not B-CLL cells) induced a dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow endothelial cells (HBMEC). It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3. In response to MM cells-increased VEGF receptors on HBMEC, endothelial cell migration was enhanced in a wound artificially produced in a semi-confluent HBMEC culture, a phenomenon which was also down-regulated by the same inhibitors that reversed the increase in VEGF receptors. The present study suggests that, in addition to the classic angiogenic pathway, another mechanism related to an increased expression of VEGFRs on HBMEC might exist in malignant hematopoietic angiogenesis.