RESUMEN
Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.
Asunto(s)
Linfoma/terapia , Trasplante de Células Madre , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/terapia , Radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Enfermedad de Hodgkin/mortalidad , Humanos , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Radioterapia/efectos adversos , Radioterapia/métodos , Planificación de la Radioterapia Asistida por Computador , Radioterapia Guiada por Imagen/métodos , Resultado del TratamientoRESUMEN
Approval of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab by the FDA in 2004 reflected the success of this vascular targeting strategy in extending survival in patients with advanced cancers. However, consistent with previous reports that experimental tumors can grow or recur during VEGF blockade, it has become clear that many patients treated with VEGF inhibitors will ultimately develop progressive disease. Previous studies have shown that disruption of VEGF signaling in tumors induces remodeling in surviving vessels, and link increased expression of angiopoietin-1 (Ang-1) with this process. However, overexpression of Ang-1 in different tumors has yielded divergent results, restricting angiogenesis in some systems while promoting it in others. These data raise the possibility that effects of Ang-1/Tie-2 may be context-dependent. Expression of an Ang-1 construct (Ang1*) did not significantly change tumor growth in our model prior to treatment, although vessels exhibited changes consistent with increased Tie-2 signaling. During inhibition of VEGF, however, both overexpression of Ang1* and administration of an engineered Ang-1 agonist (Bow-Ang1) strikingly protected tumors and vasculature from regression. In this context, Ang-1/Tie-2 activation limited tumor hypoxia, increased vessel caliber, and promoted recruitment of mural cells. Thus, these studies support a model in which activation of Tie-2 is important for tumor and vessel survival when VEGF-dependent vasculature is stressed. Understanding such mechanisms of adaptation to this validated form of therapy may be important in designing regimens that make the best use of this approach.
Asunto(s)
Angiopoyetina 1/genética , Regulación de la Expresión Génica/fisiología , Neoplasias Renales/irrigación sanguínea , Neovascularización Patológica/patología , Receptor TIE-2/genética , Sarcoma de Ewing/irrigación sanguínea , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Western Blotting , Hipoxia de la Célula , Línea Celular Tumoral , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunoprecipitación , Neoplasias Renales/patología , Ratones , Ratones Desnudos , Fosforilación , Reacción en Cadena de la Polimerasa , Sarcoma de Ewing/patología , Transfección , Trasplante Heterólogo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
As the use of lenalidomide expands, the poorly understood phenomenon of lenalidomide-induced thyroid abnormalities will increase. In this study, we compared rates of therapy-induced hypothyroidism in 329 patients with diffuse large B-cell lymphoma (DLBCL) treated with conventional chemotherapy (DLBCL-c) or conventional chemotherapy plus lenalidomide (DLBCL-len). We measured serum levels of tumor necrosis factor α, interferon gamma, interleukin 6, interleukin 12, and interleukin 15 before and after treatment. We found a significantly higher rate of therapy-induced hypothyroidism in the DLBCL-len group (25.8% vs. 1.3%), and we found a statistically significant increase in serum tumor necrosis factor α in patients with lenalidomide-induced hypothyroidism.