RESUMEN
We report herein a multicentre retrospective analysis of 192 consecutive patients with symptomatic refractory/relapsed multiple myeloma (RRMM) treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centres in Puglia. Choice of both regimens was based on previous treatment and/or physicians' preference. Considering the under-representation of older patients (very old patient ≥ 80 years) in clinical trials and the prognostic and predictive importance and value of frailty status, here, we further characterised the patient cohort by age. The overall response rate (ORR) was generally lower than what was previously reported in the CASTOR (ORR 72.6% vs 85%) and POLLUX (ORR 86.5% vs 93%) trials. The lower ORR in our analysis compared to the CASTOR and POLLUX trials could be related to a less selected population. Similarly, amongst very old patients, the ORR was encouraging: ORR to treatment with DVd (daratumumab + bortezomib + dexamethasone) was 66.7%, and ORR to treatment with DRd (daratumumab + lenalidomide + dexamethasone) was 92.3%. Median TTP (time to progression) was 10.8 months (1-year TTP: 44.7%; 2-year TTP: 25.3%) in the DVd group; median TTP was not reached in the DRd group (1-year TTP: 82.7%; 2-year TTP: 71.4%). Median OS (overall survival) was not reached either in the DRd group (1-year OS: 85.9%; 2-year OS: 73.7%) or the DVd group (1-year OS: 70.2%; 2-year OS: 58.9%).
Asunto(s)
Mieloma Múltiple , Neoplasias de Células Plasmáticas , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib , Dexametasona , Estudios de Seguimiento , Humanos , Lenalidomida , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Terapia RecuperativaRESUMEN
AIMS: All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be "regenerated" and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system. METHODS: We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels. RESULTS: We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of beta2-m and the blood loss. Furthermore, IL6 and TNFalpha decreased significantly after PDHFR treatment. CONCLUSIONS: HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and beta2-m, and the filter. Finally, it's notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.
Asunto(s)
Hemodiafiltración/métodos , Soluciones para Hemodiálisis/administración & dosificación , Uremia/terapia , Adulto , Anciano , Citocinas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Urea/sangre , Uremia/sangre , Microglobulina beta-2/sangreRESUMEN
This current retrospective multicenter analysis represents, to our knowledge, the first Italian study evaluating the efficacy and toxicity profile of "lenalidomide plus dexamethasone" as salvage therapy in patients with recurrent-refractory MM in the real life contest. Our study included patients who are usually excluded from clinical trials because of unfavorable baseline characteristics. Median OS was significantly longer in patients receiving "lenalidomide plus dexamethasone" for more than 12 months compared with those who had received "lenalidomide plus dexamethasone" for a shorter interval (P<0.0001). Median OS was not affected by best response achieved (P 0.4) and age (P 0.3). Quality of response did not correlate with number of previous lines of therapy (P 0.77) and age. Higher ORRs were recorded in the patients group with relapsed MM compared to those with refractory disease, but this difference was not statistically significant (P 0.38).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Dexametasona/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Talidomida/administración & dosificación , Talidomida/análogos & derivadosRESUMEN
The aim of this study was to analyse the relationship between dietary factors and precancerous gastric lesions in the population of a commune in the province of Latina which, on the basis of data published by RTP-LT, appears to present a striking incidence of so-called diet-dependent tumours. A series of tests was used to evaluate the antioxidising (protective) and pro-oxidising (encouraging) capacity of the following substances in terms of cancerogenesis: lutein, zeoxanthine, cryptoxanthine, lycopene, alpha and beta carotene, total carotenoids, tocopherol, retinol, ascorbic acid, cholesterol, HDL cholesterol, triglycerides and ceruloplasmin. Two sample populations were enrolled in the study: sample A (random) composed of 400 persons (202 males and 198 females) aged between 20 and 80 who underwent esophagogastroduodenoscopy and multiple biopsies of the gastric mucous; sample B (random), representative of the population, composed of 400 persons (200 males and 200 females) aged between 20 and 80, who underwent plasmatic assay of lipid and vitamin status. The results of this study appear to confirm the hypothesis of a correlation between diet and pre-cancerous lesions and suggest that the primary preventive stps take the form of: a) reduced intake of animal fat; b) increased consumption of fresh vegetables.
Asunto(s)
Dieta , Lesiones Precancerosas/etiología , Neoplasias Gástricas/etiología , Adulto , Anciano , Anciano de 80 o más Años , Dieta/efectos adversos , Grasas de la Dieta/efectos adversos , Femenino , Humanos , Italia , Lípidos/sangre , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/prevención & control , Distribución Aleatoria , Muestreo , Neoplasias Gástricas/prevención & control , Verduras , Vitaminas/sangreRESUMEN
PURPOSE: Hemodiafiltration reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We devised a new technique, post-dilution HFR, aimed at increasing the purification efficiency, treatment tolerability and at reducing inflammatory state. METHODS: We performed post-dilution HFR in six uremic patients during 18 months. Dialytic efficacy, filter blood rest and cytokine behavior were evaluated. RESULTS: Neither pyrogenic reactions nor other adverse phenomena were recorded. The tolerance to the treatment was excellent. We observed a high rate of urea extraction and optimal Kt/V values, a high extraction of beta2 microglobulin (beta2-m) and a reduction in blood rest; in addition, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) significantly decreased. CONCLUSIONS. The inversion of the standard HFR configuration allowed us to improve the removal of both urea and beta2-m, and the blood rest, with an optimal tolerability. Moreover, the reduction in cytokine levels could attenuate the uremic microinflammatory state.
Asunto(s)
Hemodiafiltración/métodos , Soluciones para Hemodiálisis/administración & dosificación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
We report one case of splenoma, a rare benign tumor of the spleen. Initial symptoms were repeated attacks of tail pancreatitis, that led to splenectomy for spontaneous splenic rupture. Splenomas may be asymptomatic or cause haematologic symptoms. Recently their association with neoplastic and haematologic disorders has been emphasized. Therefore such diseases must be ruled out when a splenoma is diagnosed.
Asunto(s)
Neoplasias del Bazo/cirugía , Rotura del Bazo/cirugía , Humanos , Masculino , Persona de Mediana Edad , Páncreas/patología , Pancreatitis/patología , Pancreatitis/cirugía , Rotura Espontánea , Bazo/patología , Esplenectomía , Neoplasias del Bazo/patología , Rotura del Bazo/patologíaRESUMEN
Two series of experiments were performed to determine whether nicergoline possesses an alpha-adrenergic blocking action on the lower urinary tract musculature in dogs and humans. One series consisted of in vivo studies of urethral pressure profile recordings in 19 female dogs, and their responses to adrenergic stimulation with noradrenaline or methoxamine, alone and following administration of nicergoline. The other series consisted of in vitro isometric studies of 61 strips of human prostate, and the establishment of dose response curves to nor-adrenaline alone and in the presence of various concentrations of nicergoline. In both sets of experiments clear evidence of an alpha-adrenergic blocking effect was obtained. From the in vitro experiments, the Kb of nicergoline was calculated as less than or equal to 9 X 10(-9) M.
Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Ergolinas/farmacología , Músculo Liso/efectos de los fármacos , Nicergolina/farmacología , Próstata/efectos de los fármacos , Uretra/efectos de los fármacos , Adenoma/fisiopatología , Animales , Perros , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Metoxamina/farmacología , Contracción Muscular/efectos de los fármacos , Norepinefrina/farmacología , Propranolol/farmacología , Neoplasias de la Próstata/fisiopatologíaRESUMEN
A double-blind crossover study of the alpha-blocker Nicergoline was carried out in sixteen patients affected by benign prostatic bladder outflow obstruction. The "irritative" symptoms of prostatic hypertrophy, including nocturnal frequency and dysuria, were improved after Nicergoline significantly more than after placebo. In 10 further patients with prostatic hypertrophy, peak and mean flow rates increased by 50% and 77% respectively after the acute administration of Nicergoline. No side effects were detected. In conclusion Nicergoline seems to be active and well tolerated in the treatment of benign prostatic obstruction.