RESUMEN
Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Estimación de Kaplan-Meier , Lenalidomida/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Proteínas de Mieloma/análisis , Oligopéptidos/administración & dosificación , Supervivencia sin Progresión , Talidomida/administración & dosificación , Talidomida/análogos & derivadosRESUMEN
RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey "do you know the radon gas?". In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018-2022.
RESUMEN
The present study aims to evaluate the possibility of constructing a new high-speed railway (HSR) at Al Sadis Min Uktober city, Cairo (Egypt): geotechnical and environmental radiological hazards are estimated from several collected soil and water samples. A variety of laboratory geotechnical tests such as grain size, free swelling test, liquid and plastic limits, chemical analysis and uniaxial compression strength are applied to sixty-one drill holes. A geotechnical examination of the coarse-grained soil at the foundation level classified it as poorly graded soil. The results of the investigation of fine-grained soil at the foundation level shown that the liquid limit ranges from 22% to 55%, the plastic limit ranges from 12% to 28%, the plasticity index varies from 11% to 33%, free swelling varies from 51% to 71%. Mechanically, the uniaxial compressive strength values on rock samples range from 6.96 MPa to 142.39 MPa. The radioactive study is performed to detect the 226Ra, 232Th, and 40 K activity concentrations of the soil samples: their mean values are 34 ± 10 Bq·kg-1, 14 ± 5 Bq·kg-1 and 552 ± 20 Bq·kg-1, respectively. The values of radiological hazard indexes are not exceeded the permissible limits: e.g. the mean value of absorbed dose rate is 47 ± 6 nGy h-1; the annual gonadal dose equivalent is 0.3 ± 0.04 mSv·y-1; the lifetime cancer risk is 02 ± 0.2·10-3. Thus, the soil in the studied railway area is safe to use in building materials and infrastructure applications: the radiological hazards and the geotechnical studies confirmed the studied area is suitable to construct a new community having a HSR. According to the SWOT-PEST and environmental impact analyses, the construction of the HSR meets the criteria of the Kyoto Protocol, the EU Climate and Energy policy, and other international treaties.
RESUMEN
The possible damaging effects on human health of inhaled radon and its decay products are of interest to workers and the public. In particular, radon in thermal environments often occurs in high concentrations. Therefore, investigations and remedial actions are important to reduce activity concentration values and associated risk. This work concerns the analysis of two surveys of radon gas activity concentration carried out in 2006/2007 and 2019/2020 at twenty thermal spas on the island of Ischia (Italy). Annual measurements were carried out in workplaces located in the basement and ground floor using passive CR-39 detectors. In the spas involved in both surveys, the effectiveness of the remedial actions, implemented by the owners, was assessed obtaining an average percentage reduction of 74%. Considerations were made about the annual effective dose, and the location of the spas taking into account the geological setting of the volcanic nature of the island.
Asunto(s)
Contaminantes Radiactivos del Aire , Contaminación del Aire Interior , Exposición Profesional , Monitoreo de Radiación , Radón , Contaminantes Radiactivos del Aire/análisis , Contaminación del Aire Interior/análisis , Humanos , Italia , Exposición Profesional/análisis , Monitoreo de Radiación/métodos , Radón/análisisRESUMEN
Although the association of bone marrow fibrosis with plasma cell dyscrasias has already been described in several reports, the close relationship between these entities still remains unclear. In this report we describe a patient with clinical and pathologic findings which initially suggested a diagnosis of myelofibrosis, subsequently shown to be coexistent with multiple myeloma. Possible explanations for this association are discussed.
Asunto(s)
Neoplasias Óseas , Mieloma Múltiple , Lesiones Precancerosas , Mielofibrosis Primaria , Médula Ósea/patología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Células Clonales/patología , Resultado Fatal , Femenino , Células Madre Hematopoyéticas/patología , Humanos , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Células Madre Neoplásicas/patología , Mielofibrosis Primaria/patologíaRESUMEN
Intermittent courses of melphalan and prednisone is still the standard chemotherapy for the initial treatment of multiple myeloma (MM) in patients who cannot undergo high-dose chemotherapy/radiotherapy with either allogeneic or autologous stem cell transplantation. However, the absorption of the drug from the gastrointestinal tract is highly variable from patient to patient and therefore, different plasma levels of the drug are reached in the blood of individual MM patients. In order to overcome this limitation we decided to use intermediate dose (15-30 mg/m2, day 1) intravenous melphalan in resistant or relapsing MM patients as well as in untreated patients not eligible for a more aggressive protocol. Moreover, considering the good results obtained by other investigators using dexamethasone alone or associated with interferon in the treatment of resistant or relapsing MM patients, dexamethasone (40 mg total dose, day 1) and the lymphoblastoid alpha interferon (3 MU, 3 times a week x 3 weeks, from day 8 to day 26 of each course) were added to intravenous melphalan. Courses were repeated every 5 weeks for a total of 6 cycles. We treated 62 MM patients obtaining a response (defined as reduction > 25% of the initial monoclonal component value associated with disappearance of the clinical symptoms) in 38 out 62 evaluable patients (61%) and stable disease (defined as a decrease of < 25% in the base-line serum monoclonal component level with disappearance of all symptoms present at diagnosis) in 9 (14.5%) more patients. The overall median response duration was 14 months and the overall median survival duration (from the time of inclusion in this protocol) for the 62 patients entered into the study was 34 months. No severe (Grade 3-4 of the WHO) hematological as well as non hematological toxicities were observed. This lack of severe toxicity allowed us to administer the drugs on an outpatient basis. In conclusion, the overall response and the low grade of toxicity in this category of patients are encouraging and suggest that this protocol is both effective and safe treatment for high risk MM patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Análisis Actuarial , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Estudios de Cohortes , Dexametasona/administración & dosificación , Dexametasona/toxicidad , Supervivencia sin Enfermedad , Evaluación de Medicamentos , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/toxicidad , Leucopenia/inducido químicamente , Masculino , Melfalán/administración & dosificación , Melfalán/toxicidad , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Recurrencia , Factores de Riesgo , Sepsis/inducido químicamente , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
Starting from May, 1991, 35 untreated myeloma patients entered a multicentric pilot study to evaluate the feasibility of a program of PBSC transplantation for previously untreated myeloma patients. The schedule was as follows: 2 cycles of VAD followed by CY, 7 g/mq+G-CSF (Granulokine, Roche) for 14 days, to increase and collect PBSC. The subsequent conditioning regimen was Melphalan+Busulfan followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The median follow-up is 14 months (4-22). On April 1993, 34 patients received at least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received conditioning regimen plus PBSC and 16 of them are in the maintenance treatment with IFN. Considering 28 patients for an intention to treat evaluation (35-7 in treatment), responding patients are 71% with 46% who achieved CR. White cells and platelets raised to > 1000/mmc and > 50,000/mmc after a median period of 10 and 13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients relapsed, 2 others died while in PR because of CMV epatitis and candida pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 10(6)/kg b.w. and 28.1 x 10(4)/kg b.w. respectively. In conclusion this treatment seems to be feasible and with low toxicity, but a longer follow-up is needed to evaluate the progression free survival of the high proportion of responding patients that we observed.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Eliminación de Componentes Sanguíneos , Ciclofosfamida/administración & dosificación , Dexametasona , Doxorrubicina/administración & dosificación , Estudios de Factibilidad , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
The association of melphalan and prednisone, introduced in the sixties, allowed a dramatic improvement in the prognosis of multiple myeloma. The subsequent evaluation of different polychemotherapeutic schedules did not ameliorate the results with respect to the melphalan-prednisone association, which remains the treatment of choice in patients older than 60-65 years. In younger patients high dose therapy allowed, in the recent years, significant improvement in terms of reduction of tumor mass and survival. The use of interferon as maintenance treatment allowed a prolongation of the response phase obtained after induction treatment. In this paper we discuss current trends in the management of multiple myeloma and related complication.
Asunto(s)
Mieloma Múltiple/terapia , Adulto , Factores de Edad , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Humanos , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Prednisona/administración & dosificación , Pronóstico , Factores de TiempoRESUMEN
Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease.
Asunto(s)
Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Humanos , Interferón-alfa/uso terapéutico , Cariotipificación , Melfalán/uso terapéutico , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Fenotipo , Prednisona/uso terapéutico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Amiloidosis/tratamiento farmacológico , Ácidos Borónicos/uso terapéutico , Dexametasona/uso terapéutico , Cadenas Ligeras de Inmunoglobulina , Pirazinas/uso terapéutico , Anciano , Amiloidosis/inmunología , Amiloidosis/fisiopatología , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/efectos adversos , Bortezomib , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Quimioterapia Combinada , Ecocardiografía , Femenino , Humanos , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , RecurrenciaRESUMEN
We report a study undertaken to test the biological effect of intranasal 1-deamino-8-D-arginine vasopressin (DDAVP) and its efficacy in the treatment of bleedings in patients with mild factor VIII deficiency. The biological study was carried out in 20 patients: an increase of factor VIII:C and von Willebrand factor antigen levels was observed after inhalation of DDAVP at average post/pre inhalation ratios of 2.80 and 1.72, respectively. No relevant alterations of fibrinolysis were noted. In fact, we only observed a simultaneous increase of tissue plasminogen activator and plasminogen activator inhibitor, without modification of D-dimer. In 10 cases intranasal DDAVP has been used in the prevention or in the treatment of bleeding complications: no bleedings were observed.
Asunto(s)
Desamino Arginina Vasopresina/uso terapéutico , Hemofilia A/terapia , Hemorragia/prevención & control , Factores Inmunológicos/uso terapéutico , Administración Intranasal , Adolescente , Adulto , Niño , Desamino Arginina Vasopresina/administración & dosificación , Evaluación de Medicamentos , Factor VIII/análisis , Fibrinólisis , Hemofilia A/sangre , Humanos , Factores Inmunológicos/administración & dosificación , Persona de Mediana EdadRESUMEN
A case of disseminated intravascular coagulation (DIC) and fatal myocardial infarction in a haemophilia B patient is described. DIC occurred after 4 days of therapy with unactivated prothrombin complex concentrates during the post-operative period. Therapy with fresh frozen plasma, heparin and antithrombin III concentrates was started without efficacy; after autopsy myocardial infarction was evident.
Asunto(s)
Factores de Coagulación Sanguínea/efectos adversos , Coagulación Intravascular Diseminada/etiología , Hemofilia B/tratamiento farmacológico , Infarto del Miocardio/etiología , Factores de Coagulación Sanguínea/uso terapéutico , Hemofilia B/complicaciones , Hernia Inguinal/complicaciones , Hernia Inguinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Cuidados PreoperatoriosRESUMEN
We report a study concerning 100 patients affected by essential thrombocythemia: 90 adult (age greater than 20 years) and 10 pediatric subjects. The diagnosis was made by chance (78%), because of hemorrhages (10%), thrombosis (9%), vasomotor symptoms (29%). In the adult group, single-agent chemotherapy was performed with good remission using pipobroman or interferon. Antiaggregant agents were used in all patients at diagnosis. During the clinical course only a few complications occurred.
Asunto(s)
Trombocitemia Esencial/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Busulfano/uso terapéutico , Niño , Preescolar , Trastornos Hemorrágicos/etiología , Humanos , Hidroxiurea/uso terapéutico , Interferón Tipo I/uso terapéutico , Italia/epidemiología , Leucemia/etiología , Persona de Mediana Edad , Pipobromán/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Proteínas Recombinantes , Estudios Retrospectivos , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/tratamiento farmacológico , Tromboembolia/etiología , Tromboembolia/prevención & controlRESUMEN
Sixty probable carriers of haemophilia from 25 families were studied by using coagulation phenotype and DNA analysis: 33 with haemophilia A and 27 with haemophilia B. Coagulation phenotype was based on factor VIII/IX assay and DNA analysis on the examination of restriction fragment length polymorphisms (RFLPs) within and closely linked to factor VIII or IX: 3 RFLP for factor VIII and 3 for factor IX. The comparison between the coagulation phenotype and RFLP analysis showed the misclassification of 15 females (6 for haemophilia A and 9 for haemophilia B). Four prenatal haemophilia A diagnosis were made by DNA analysis of chorionic villi, taken with a transcervical trophoblastic biopsy, between the 18th and the 11th week.