Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
Am J Hematol ; 98(2): 264-271, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36588407

RESUMEN

Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.


Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Niño , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Paraproteinemias/genética , Paraproteinemias/complicaciones , Mieloma Múltiple/patología , Pronóstico , Aberraciones Cromosómicas
3.
Bull Acad Natl Med ; 190(4-5): 981-92; discussion 993-4, 2006.
Artículo en Francés | MEDLINE | ID: mdl-17195622

RESUMEN

Non steroidal antiinflammatory drugs (NSAID) used to be the only drugs active in ankylosing spondylarthritis (AS). However, they are inadequate or ill-tolerated in many patients, and have no proven impact on disease-related structural changes. Clinical trials have recently shown the impressive efficacy of two anti-TNFalpha agents (infliximab and etanercept) in patients with NSAID-resistant SA. These drugs attenuate inflammatory pain, stiffness and functional disability, and improve mobility and quality of life. Tolerability is satisfactory, and efficacy persists during several years of treatment. Moreover, these agents induce regression of acute inflammatory lesions, as demonstrated by magnetic resonance imaging (MRI). A 2-year X-ray study indicates that they also slow the progression of structural lesions. More studies are needed to determine the precise place of anti-TNFalpha agents in this setting.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales/administración & dosificación , Antirreumáticos/administración & dosificación , Ensayos Clínicos como Asunto , Etanercept , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/administración & dosificación , Infliximab , Masculino , Radiografía , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento
4.
J Clin Oncol ; 34(30): 3609-3617, 2016 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-27325857

RESUMEN

Purpose This analysis of the FIRST trial in patients with newly diagnosed multiple myeloma (MM) ineligible for stem-cell transplantation examined updated outcomes and impact of patient age. Patients and Methods Patients with untreated symptomatic MM were randomly assigned at a one-to-one-to-one ratio to lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks), stratified by age (≤ 75 v > 75 years), disease stage (International Staging System stage I/II v III), and country. The primary end point was progression-free survival. Rd continuous and MPT were primary comparators. Results Between August 21, 2008, and March 7, 2011, 1,623 patients were enrolled (Rd continuous, n = 535; Rd18, n = 541; MPT, n = 547), including 567 (35%) age older than 75 years. Higher rates of advanced-stage disease and renal impairment were observed in patients older than 75 versus 75 years of age or younger. Rd continuous reduced the risk of progression or death compared with MPT by 31% (hazard ratio [HR], 0.69; 95% CI, 0.59 to 0.80; P < .001) overall, 36% (HR, 0.64; 95% CI, 0.53 to 0.77; P < .001) in patients age 75 years or younger, and 20% (HR, 0.80; 95% CI, 0.62 to 1.03; P = .084) in those age older than 75 years. Median overall survival was longer with Rd continuous than with MPT, including a 14-month difference in patients age older than 75 years. Progression-free survival with Rd18 was similar to that with MPT, and overall survival with Rd18 was marginally inferior to that with Rd continuous. Rates of grade 3 to 4 treatment-emergent adverse events were similar for Rd continuous-treated patients age 75 years or older and those age older than 75 years; however, older patients had more frequent lenalidomide dose reductions. Conclusion Results support Rd continuous treatment as a new standard of care for stem-cell transplantation-ineligible patients with newly diagnosed MM of all ages.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Lenalidomida , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Prednisona/administración & dosificación , Tasa de Supervivencia , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/análogos & derivados
6.
Joint Bone Spine ; 77(1): 20-6, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20031467

RESUMEN

The management of multiple myeloma has benefited substantially from the introduction of three new drugs, namely, the proteasome inhibitor bortezomib and the immunomodulators thalidomide and lenalidomide. These drugs were initially shown to improve the outcome of advanced myeloma and were subsequently found to transform the treatment of patients with previously untreated myeloma. Melphalan and prednisone combined with thalidomide or bortezomib is the new treatment of reference for patients who are elderly or ineligible for intensification. The introduction of these new drugs into induction regimens, intensified conditioning regimens, and posttransplantation regimens may improve overall survival among young patients by increasing the rate and quality of the treatment responses. Although myeloma remains incurable, prolonged survival is now a reasonable objective.


Asunto(s)
Mieloma Múltiple/tratamiento farmacológico , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Ácidos Borónicos/uso terapéutico , Bortezomib , Quimioterapia Combinada , Humanos , Inmunosupresores/uso terapéutico , Lenalidomida , Melfalán/uso terapéutico , Mieloma Múltiple/inmunología , Mieloma Múltiple/mortalidad , Agonistas Mieloablativos/uso terapéutico , Estadificación de Neoplasias , Prednisona/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Pirazinas/uso terapéutico , Tasa de Supervivencia
7.
Joint Bone Spine ; 76(1): 28-34, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19059799

RESUMEN

OBJECTIVE: To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy METHODS: French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. RESULTS: Spondylarthropathies (n=8), rheumatoid arthritis (n=4), juvenile idiopathic arthritis (n=2), and psoriatic arthritis (n=1) were treated by infliximab (n=3), adalimumab (n=2), or etanercept (n=10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. CONCLUSION: The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Adulto , Artritis/complicaciones , Artritis Juvenil/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Femenino , Edad Gestacional , Humanos , Recién Nacido , Intercambio Materno-Fetal , Embarazo , Efectos Tardíos de la Exposición Prenatal , Encuestas y Cuestionarios , Adulto Joven
8.
J Clin Oncol ; 27(22): 3664-70, 2009 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-19451428

RESUMEN

PURPOSE: Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. PATIENTS AND METHODS: Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. RESULTS: After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). CONCLUSION: This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Causas de Muerte , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Evaluación Geriátrica , Humanos , Estimación de Kaplan-Meier , Masculino , Dosis Máxima Tolerada , Melfalán/administración & dosificación , Melfalán/efectos adversos , Mieloma Múltiple/patología , Estadificación de Neoplasias , Prednisona/administración & dosificación , Prednisona/efectos adversos , Probabilidad , Modelos de Riesgos Proporcionales , Medición de Riesgo , Estadísticas no Paramétricas , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/efectos adversos , Resultado del Tratamiento
9.
Blood ; 109(8): 3489-95, 2007 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-17209057

RESUMEN

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.


Asunto(s)
Aberraciones Cromosómicas , Modelos Biológicos , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Tasa de Supervivencia
10.
Blood ; 107(4): 1292-8, 2006 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-16174762

RESUMEN

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myélome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/administración & dosificación , Melfalán/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Anciano , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Infecciones/epidemiología , Interferón-alfa/administración & dosificación , Masculino , Melfalán/efectos adversos , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Selección de Paciente , Prednisona/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento
11.
Ann Hematol ; 84(1): 19-24, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15338198

RESUMEN

Bone disease is a common feature of multiple myeloma (MM). The goal of this study was to assess the prognostic significance of urinary markers of bone metabolism in MM. Urinary levels of total pyridinoline (T-Pyd), deoxypyridinoline (T-Dpd), crosslinked N-telopeptide (Ntx), C-telopeptide (Ctx) of type I collagen and immunologic free deoxypyridinoline (f-Dpd) were assessed in 82 consecutive, previously untreated MM patients (aged 65-75 years) diagnosed between June 1995 and December 1998. A correlation between disease stage according to the Durie-Salmon classification and T-Pyd (p=0.034) and T-Dpd (p=0.007) was observed, while T-Pyd (p=0.015) and to a lesser extent f-Dpd (p=0.081) were correlated to bone involvement measured by plain X-ray. None were correlated to M-component or magnetic resonance imaging (MRI). In univariate analysis high T-Pyd (p=0.007), T-Dpd (p=0.027), f-Dpd (p<0.001), and Ctx (p=0.011) were associated with shorter overall survival, whereas only f-Dpd (p=0.0025) was associated with a shorter disease-free survival. In multivariate analysis, C-reactive protein and f-Dpd were independent prognostic factors for overall survival. This retrospective analysis defined new independent prognostic indicators of survival in patients with newly diagnosed myeloma. Indeed, urinary markers of bone resorption can easily be measured at diagnosis and have independent prognostic significance to refine the prognosis of MM patients.


Asunto(s)
Resorción Ósea/diagnóstico , Mieloma Múltiple/complicaciones , Compuestos de Piridinio/orina , Anciano , Aminoácidos/orina , Biomarcadores/orina , Resorción Ósea/etiología , Resorción Ósea/orina , Colágeno/orina , Colágeno Tipo I , Femenino , Humanos , Masculino , Mieloma Múltiple/mortalidad , Mieloma Múltiple/orina , Péptidos/orina , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
12.
Eur J Intern Med ; 13(2): 85-95, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11893464

RESUMEN

Until 1990, the melphalan-prednisone regimen was the standard treatment for multiple myeloma (MM). The role of alpha-interferon still remains controversial, both in induction therapy and in maintenance therapy. Over the last 10 years, there has been considerable improvement in the treatment of MM. In patients under 65 years of age, high-dose therapy with autografting has clearly demonstrated an advantage over conventional treatment. Bisphosphonates have proved very useful in reducing skeletal events. More recently, an old drug, thalidomide, has shown surprising efficacy in patients with advanced MM. Future trends include the extension of high-dose therapy to older patients and the use of immunotherapy in induction and/or maintenance therapy.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA