RESUMEN
BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.
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Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Linfoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de la Retina/tratamiento farmacológico , Terapia Recuperativa , Adenina/análogos & derivados , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/patología , Femenino , Estudios de Seguimiento , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Piperidinas , Pronóstico , Estudios Prospectivos , Neoplasias de la Retina/patología , Tasa de SupervivenciaAsunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Púrpura Trombocitopénica Idiopática/inducido químicamente , Púrpura Trombocitopénica Idiopática/inmunología , Adulto , Antígenos de Plaqueta Humana/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Resultado Fatal , Antígenos HLA/inmunología , Humanos , MasculinoAsunto(s)
Neoplasias Hematológicas , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Servicios de Atención de Salud a Domicilio , Trasplante de Células Madre de Sangre Periférica , Autoinjertos , Bencilaminas , Ciclamas , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/terapia , Vigilancia de Productos Comercializados , Sistema de RegistrosAsunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Hematológicas/terapia , Hematopoyesis , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Autoinjertos , Bencilaminas , Ciclamas , Femenino , Humanos , Masculino , Vigilancia de Productos ComercializadosRESUMEN
Background: Plasmablastic lymphoma (PBL), initially described in 1997 in the oral cavity of HIV positive patients, is now recognized as a distinct aggressive and rare entity of diffuse large B-cells lymphoma by the World Health Organization (WHO) classification. Since the original description, others cases have been reported. However, these are largely derived from case reports or small series limiting any definitive conclusions on clinical characteristics and outcome. Patients and methods: The clinical, biological, pathological features and outcome of a cohort including 135 patients with PBL, from LYSA centers in France and Belgium, were reported and analyzed. Results: The median age was 58 years, with a male predominance. The cohort was divided into 56 HIV-positive patients, 17 post-transplant patients and 62 HIV-negative/non-transplanted patients. Within HIV-negative/non-transplanted, a relative immunosuppression was found in most cases (systemic inflammatory disease, history of cancer, increased age associated with weakened immune system). We have also described a new subtype, PBL arising in a chronic localized inflammatory site, without any sign of immunosuppression. At presentation, 19% of patients showed oral involvement. Immunophenotype showed CD138 positivity in 88% of cases and CD20 negativity in 90% of cases. Chemotherapy was administered to 80% of patients, with a complete response (CR) rate of 55%. The median overall survival (OS) was 32 months. In univariate analysis, HIV positive status showed better OS when compared with HIV negative status. In multivariate analysis, International Prognostic Index score, chemotherapy and CR were associated with survival benefit. Conclusion(s): This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.
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Linfoma Plasmablástico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Bélgica , Comorbilidad , Femenino , Francia , Infecciones por VIH/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Linfoma Plasmablástico/epidemiología , Linfoma Plasmablástico/inmunología , Linfoma Plasmablástico/patología , Modelos de Riesgos Proporcionales , Receptores de Trasplantes , Adulto JovenRESUMEN
High-dose chemotherapy with stem cells support has largely improved in terms of hematopoietic stem and progenitor cells harvest procedures as well as in those, which target or manipulate the cellular composition of autologous graft. Optimal preparative regimens and supportive care had lead to better use of autologous transplantation procedure. For other patients assigned to hematopoietic transplantation, availability of allogeneic donors appears to be an interesting alternative source of hematopoietic stem cells. Since three decades, hematopoietic growth factors development has allowed mobilization optimization and collection of peripheral hematopoietic stem cells leading to reduced days of hospitalization and less blood products requirements, being more cost-effective for patients in autologous transplantation settings and for stem cell collection facilities in allogeneic ones. New perspectives include, besides ex vivo manipulation of graft, development of mobilizing drugs in order to perform transplantation even in poor mobilizers patients. An important goal is achieved with the description of genetic polymorphisms related to optimal mobilization of stem cells. New approach using more promising and selective agents called chemokines, such as plerixafor the main leader among these agents are now available and appear complementary for alternative approach using cytokines alone (G-CSF, GM-CSF, SCF). The aim of this review is to assess the evolution of theses biotechnologies and their role in different steps of autologous transplantation and allogeneic stem cells collection.
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Movilización de Célula Madre Hematopoyética , Bencilaminas , Eliminación de Componentes Sanguíneos , Moléculas de Adhesión Celular/antagonistas & inhibidores , Quimiocinas/farmacología , Ciclamas , Filgrastim , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Hormona del Crecimiento/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Movilización de Célula Madre Hematopoyética/tendencias , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos/farmacología , Humanos , Hormona Paratiroidea/farmacología , Polietilenglicoles , Receptores de Quimiocina/antagonistas & inhibidores , Proteínas Recombinantes/farmacología , Factor de Células Madre/farmacología , Trasplante AutólogoRESUMEN
INTRODUCTION: The combination of neurofibromatosis type I with hyperparathyroidism is classical but rare. OBSERVATION: Our report is on the original observation of a patient affected with Von Recklinghausen's disease complicated by chronic restrictive breathing deficiency. After an intense breathing decompensation and a spreading convulsive attack, hyperparathyroidism was diagnosed. DISCUSSION: The similarity of the bone lesions seen in type I neurofibromatosis and in hyperparathyroidism strongly suggests a genetic link between these two pathologies. Hence, hyperparathyroidism should be searched for in all patients affected with Von Recklinghausen's disease, since the adjustment of hypercalcemia can lead to partial reversibility of the bone abnormalities.