RESUMEN
This randomized, noninferiority (NI), global, phase 3 study evaluated the efficacy and safety of bendamustine plus rituximab (BR) vs a standard rituximab-chemotherapy regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] or rituximab plus cyclophosphamide, vincristine, and prednisone [R-CVP]) for treatment-naive patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma. Investigators preassigned the standard treatment regimen they considered most appropriate for each patient; patients were randomized to receive BR (n = 224) or standard therapy (R-CHOP/R-CVP, n = 223) for 6 cycles; 2 additional cycles were permitted at investigator discretion. Response was assessed by a blinded independent review committee. BR was noninferior to R-CHOP/R-CVP, as assessed by the primary end point of complete response rate (31% vs 25%, respectively; P = .0225 for NI [0.88 margin]). The overall response rates for BR and R-CHOP/R-CVP were 97% and 91%, respectively (P = .0102). Incidences of vomiting and drug-hypersensitivity reactions were significantly higher in patients treated with BR (P < .05), and incidences of peripheral neuropathy/paresthesia and alopecia were significantly higher in patients treated with standard-therapy regimens (P < .05). These data indicate BR is noninferior to standard therapy with regard to clinical response with an acceptable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT00877006.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Alopecia/inducido químicamente , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Esquema de Medicación , Fatiga/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Compuestos de Mostaza Nitrogenada/administración & dosificación , Compuestos de Mostaza Nitrogenada/efectos adversos , Parestesia/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Prednisona/administración & dosificación , Prednisona/efectos adversos , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vómitos/inducido químicamenteAsunto(s)
Vértebras Lumbares/diagnóstico por imagen , Mieloma Múltiple/diagnóstico por imagen , Mieloma Múltiple/mortalidad , Osteoporosis/diagnóstico por imagen , Osteoporosis/mortalidad , Anciano , Trasplante de Médula Ósea , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Mieloma Múltiple/terapia , Osteoporosis/etiología , Estudios Prospectivos , Trasplante de Células Madre , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Trasplante HomólogoRESUMEN
The confinement of multiple myeloma (MM) to the bone marrow microenvironment requires an invasive bone marrow biopsy to monitor the malignant compartment. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity mainly because they indirectly measure tumor burden inside the bone marrow and fail to capture the patchy, multisite tumor infiltrates associated with MM. Microparticles (MPs) are 0.1- to 1.0-µm membrane vesicles, which contain the cellular content of their originating cell. MPs are functional mediators and convey prothrombotic, promalignant, proresistance, and proinflammatory messages, establishing intercellular cross talk and bypassing the need for direct cell-cell contact in many pathologies. In this study, we analyzed plasma cell-derived MPs (CD138(+)) from deidentified MM patients (n = 64) and normal subjects (n = 18) using flow cytometry. The morphology and size of the MPs were further analyzed using scanning electron microscopy. Our study shows the proof of a systemic signature of MPs in MM patients. We observed that the levels of MPs were significantly elevated in MM corresponding to the tumor burden. We provide the first evidence for the presence of MPs in the peripheral blood of MM patients with potential applications in personalized MM clinical monitoring.
Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Mieloma Múltiple/metabolismo , Sindecano-1/metabolismo , Biopsia , Médula Ósea/patología , Micropartículas Derivadas de Células/ultraestructura , Femenino , Citometría de Flujo , Humanos , Persona de Mediana Edad , Mieloma Múltiple/patología , Mieloma Múltiple/terapiaRESUMEN
Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn's disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn's disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease.