RESUMEN
The programmed-death-1 inhibitors selectively block programmed-death-1 interaction with its receptor, which restores active T-cell response directed at tumor cells, inducing an anti-tumor effect. This nonspecific activation of the immune system can also lead to a wide spectrum of side effects. Nivolumab has been used effectively to prolong survival in patients with metastatic melanoma and is recommended as a category 1 agent for systemic therapy in metastatic or unresectable melanoma per the National Comprehensive Cancer Network guidelines. We present a case of a 64-year-old woman who began nivolumab therapy for metastatic melanoma. After six doses of nivolumab therapy, the patient experienced generalized hypopigmentation on her face, chest, back, arms, and lower extremities. Although vitiligo has been reported in as many as 10.7% of patients undergoing nivolumab therapy in some clinical trials, we believe this is the first case to describe the progression of nivolumab-induced vitiligo in a metastatic melanoma patient. This case provides significant insight into the onset, symptoms, development, and treatment options for patients experiencing vitiligo as a result of nivolumab therapy.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Vitíligo/inducido químicamente , Vitíligo/diagnóstico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Femenino , Humanos , Melanoma/diagnóstico , Persona de Mediana Edad , Nivolumab , Neoplasias Cutáneas/diagnósticoAsunto(s)
Terapias Complementarias/estadística & datos numéricos , Linfoma , Sobrevivientes/estadística & datos numéricos , Adulto , Anciano , Niño , Comunicación , Terapias Complementarias/clasificación , Terapias Complementarias/psicología , Cultura , Estudios de Seguimiento , Conocimientos, Actitudes y Práctica en Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Linfoma/clasificación , Linfoma/psicología , Linfoma/terapia , Persona de Mediana Edad , Relaciones Médico-Paciente , Fitoterapia/estadística & datos numéricos , Calidad de Vida , Encuestas y Cuestionarios , Sobrevivientes/psicología , Poblaciones VulnerablesRESUMEN
Exogenous heparin exposure is the major risk factor for heparin-induced thrombocytopenia and thrombosis (HITT). To date, only five cases of 'spontaneous' HITT have been reported in the literature. We report the case of a 60-year-old man who developed severe thrombocytopenia (15 000/µl) and bilateral deep venous thromboses 10 days after bilateral knee replacement. There was no evidence of heparin exposure upon review of the patient's preoperative and postoperative medication history. Heparin: platelet factor-4 (PF4) antibodies were positive as was the serotonin release assay. Anticoagulation with argatroban along with prednisone and intravenous immune globulin were administered. Anticoagulation with argatroban was bridged to warfarin once his platelet count reached 100 000/µl, and he was continued on oral prednisone taper. Heparin: PF4 antibodies were negative 3 months after the event. Six months later, Doppler ultrasound revealed deep vein thrombosis. This case represents a third 'spontaneous' episode of HITT in the context of knee replacement surgery without heparin administration. It is unclear whether these cases are a result of exposure to a heparin-like proteoglycan such as chondroitin sulfate during surgery that binds PF4, or whether the perioperative pro-inflammatory milieu is the inciting event. Further consideration of precipitating events in these individuals merits further investigation and may lead to valuable insight into the pathophysiology of heparin-independent PF4-related thrombocytopenia and thrombosis.
Asunto(s)
Anticoagulantes/inmunología , Artroplastia de Reemplazo de Rodilla , Autoanticuerpos/inmunología , Heparina/inmunología , Factor Plaquetario 4/inmunología , Trombocitopenia/inmunología , Trombosis de la Vena/inmunología , Antitrombinas/uso terapéutico , Arginina/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Ácidos Pipecólicos/uso terapéutico , Sulfonamidas , Trombocitopenia/patologíaRESUMEN
We report that heat shock protein 90 (Hsp90) inhibitors selectively kill diffuse large B cell lymphomas (DLBCLs) that depend on the BCL-6 transcriptional repressor. We found that endogenous Hsp90 interacts with BCL-6 in DLBCL cells and can stabilize BCL-6 mRNA and protein. Hsp90 formed a complex with BCL-6 at its target promoters, and Hsp90 inhibitors derepressed BCL-6 target genes. A stable mutant of BCL-6 rescued DLBCL cells from Hsp90 inhibitor-induced apoptosis. BCL-6 and Hsp90 were almost invariantly coexpressed in the nuclei of primary DLBCL cells, suggesting that their interaction is relevant in this disease. We examined the pharmacokinetics, toxicity and efficacy of PU-H71, a recently developed purine-derived Hsp90 inhibitor. PU-H71 preferentially accumulated in lymphomas compared to normal tissues and selectively suppressed BCL-6-dependent DLBCLs in vivo, inducing reactivation of key BCL-6 target genes and apoptosis. PU-H71 also induced cell death in primary human DLBCL specimens.