RESUMEN
Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen®). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m2 intravenously on day 1 and either original filgrastim (n = 61;58%) or biosimilar filgrastim (n = 44;42%) at a dose of 5 µg per kg body weight (BW) twice daily subcutaneously starting day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4 × 106 HPC/kg BW were collected. All patients proceeded to leukapheresis. In 102 (97%) patients the leukapheresis sessions were started as planned at day 8. The median number of collected HPC was 7.3 × 106 /kg BW (0.2-18.3) with original filgrastim compared to 9 × 106 /kg BW (4.2-23.8) with the biosimilar filgrastim (P = 0.16). HPC collection was successful in 57 (93%) of 61 patients of the original group and in all 44 (100%) patients of the biosimilar group (P = 0.14). No differences were observed regarding side effects. Duration of neutrophil engraftment after autologous HPC transplantation was similar between the two groups (P = 0.17). Biosimilar and original filgrastim achieve comparable results in combination with vinorelbine regarding HPC mobilization and transplantation outcome in multiple myeloma patients. J. Clin. Apheresis 32:21-26, 2017. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Biosimilares Farmacéuticos/farmacología , Filgrastim/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Vinblastina/análogos & derivados , Biosimilares Farmacéuticos/administración & dosificación , Recuento de Células , Protocolos Clínicos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Filgrastim/administración & dosificación , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Estudios Retrospectivos , Vinblastina/administración & dosificación , Vinblastina/farmacología , VinorelbinaRESUMEN
We aimed to assess the efficacy of vinorelbine plus granulocyte colony-stimulating factor (G-CSF) for chemo-mobilization of CD34(+) hematopoietic progenitor cells (HPC) in patients with multiple myeloma and to identify adverse risk factors for successful mobilization. Vinorelbine 35 mg/m(2) was administered intravenously on day 1 in an outpatient setting. Filgrastim 5 µg/kg body weight (BW) was given twice daily subcutaneously from day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and be performed for a maximum of 3 consecutive days until at least 4 × 10(6) CD34(+) cells per kg BW were collected. Overall, 223 patients were mobilized and 221 (99%) patients proceeded to leukapheresis. Three (1.5%) patients required an unscheduled hospitalization after chemo-mobilization because of neutropenic fever and renal failure (n = 1), severe bone pain (n = 1), and abdominal pain with constipation (n = 1). In 211 (95%) patients, the leukaphereses were started as planned at day 8, whereas in 8 (3%) patients the procedure was postponed to day 9 and in 2 (1%) patients to day 10. In the great majority of patients (77%), the predefined amount of HPC could be collected with 1 leukapheresis. Forty-four (20%) patients needed a second leukapheresis, whereas only 6 (3%) patients required a third leukapheresis procedure. The median number of CD34(+) cells collected was 6.56 × 10(6) (range, .18 to 25.9 × 10(6)) per kg BW at the first day of leukapheresis and 7.65 × 10(6) (range, .18 to 25.9 × 10(6)) per kg BW in total. HPC collection was successful in 212 (95%) patients after a maximum of 3 leukaphereses. Patient age (P = .02) and prior exposition to lenalidomide (P < .001) were independent risk factors for a lower HPC amount collected in multiple regression analysis. Vinorelbine plus G-CSF enables a very reliable prediction of the timing of leukapheresis and results in successful HPC collection in 95% of the patients.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/inmunología , Mieloma Múltiple/terapia , Vinblastina/análogos & derivados , Adulto , Factores de Edad , Anciano , Antígenos CD34/genética , Antígenos CD34/inmunología , Recuento de Células , Quimioterapia Combinada , Femenino , Filgrastim , Expresión Génica , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Lenalidomida , Leucaféresis , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Talidomida/efectos adversos , Talidomida/análogos & derivados , Trasplante Autólogo , Resultado del Tratamiento , Vinblastina/uso terapéutico , VinorelbinaRESUMEN
The purpose of the study was to further scrutinize the potential of ßB2-crystallin in supporting regeneration of injured retinal ganglion cell axons both in vitro and in vivo. Retinal explants obtained from animals after treatment either with lens injury (LI) alone or with combined LI 5 days or 3 days before or simultaneously with an optic nerve crush (ONC) were cultured for 96 h under regenerative conditions, and the regenerating axons were quantified and compared with untreated controls. These measurements were then repeated with LI replaced by intravitreal injections of γ-crystallin and ß-crystallin at 5 days before ONC. Finally, ßB2-crystallin-overexpressing transfected neural progenitor cells (ßB2-crystallin-NPCs) in the eye were studied after crushing the optic nerve in vivo. Regeneration was monitored with the aid of immunoblotting of the retina and optic nerve both distal and proximal to the lesion site, and this was compared with controls that received injections of phosphate buffer only. LI performed 5 days or 3 days before ONC significantly promoted axonal outgrowth in vitro (p < 0.001), while LI performed alone before explantation did not. Intravitreal injections of ß-crystallin and γ-crystallin mimicked the effects of LI and significantly increased axonal regeneration in culture at the same time intervals (p < 0.001). Western blot analysis revealed that crystallins were present in the proximal optic nerve stump at the lesion site in ONC, but were neither expressed in the undamaged distal optic nerve nor in uninjured tissue. ßB2-crystallin-NPCs supported the regeneration of cut optic nerve axons within the distal optic nerve stump in vivo. The reported data suggest that ßB2-crystallin-producing "cell factories" could be used to provide novel therapeutic drugs for central nervous system injuries.
Asunto(s)
Traumatismos del Nervio Óptico/terapia , Nervio Óptico/patología , Células Ganglionares de la Retina/trasplante , Cadena B de beta-Cristalina/metabolismo , Animales , Axones/fisiología , Células Cultivadas , Inmunohistoquímica , Inyecciones Intravenosas , Inyecciones Intravítreas , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Células-Madre Neurales/trasplante , Nervio Óptico/metabolismo , Ratas , Ratas Sprague-Dawley , Regeneración , Retina/metabolismo , Retina/patología , Células Ganglionares de la Retina/citología , Cadena B de beta-Cristalina/administración & dosificación , Cadena B de beta-Cristalina/genética , gamma-Cristalinas/administración & dosificación , gamma-Cristalinas/genética , gamma-Cristalinas/metabolismoRESUMEN
Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life.
RESUMEN
PURPOSE: Crystallin ß-b2 (crybb2) is known to support the regeneration of retinal ganglion cell (RGC) axons in culture. We investigated whether neuronal progenitor cells (NPCs) overexpressing crybb2 (crybb2-NPC) affect secondary retinal degeneration due to optic nerve crush in vivo. METHODS: NPCS were produced by dissociation and propagation of rat embryonic neural tube and eye primordial cells at embryonic days 13.5 and 15. Retinal degeneration was induced by injured optic nerve crush (BY suture, 20 seconds). Several groups were built: crybb2-NPC were injected into the vitreous body, while the Controls were comprised of recombinant crybb2-injected and PBS-injected groups. The eyes, in particular the retina, were analyzed by immunohistochemistry and Western blotting for different antigens at 2 and 4 weeks after surgery. RESULTS: At 2 and 4 weeks post surgery, crybb2-NPC resided within the vitreoretinal compartment, and were persistently nestin-positive throughout the experimental period. The cells stained positive for various neurotrophins and acted as "living" cell factories to support the survival of injured RGCs. The crybb2-NPC migrated throughout the eye structures and sometimes became integrated within the tissue. Most of the ocular cells responded to the appearance of crybb2-NPC with marked changes of certain proteins, including Iba-1 (microglia), vimentin (glial cells), and rhodopsin (photoreceptors). Photoreceptors also displayed a better survival after crybb2-NPC injection compared to control groups. CONCLUSIONS: Crybb2-NPC exert beneficial effects on the vitreoretinal compartment, which suggests that modified crybb2-NPC could be used in a novel strategy for the treatment of degenerative vitreoretinal diseases. However, future studies must determine the safety of in vivo administration of crybb2-NPC.