RESUMEN
An inappropriate interferon-gamma response has been implicated in the pathogenesis of severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI). To assess whether this is unique for RSV primary LRTI compared to a first non-RSV LRTI, intracellular interferon-gamma was determined by flow cytometry in peripheral blood mononuclear cells from 32 infants with a primary RSV infection, 28 with a first non-RSV LRTI due to adenoviral, parainfluenzaviral and rhinoviral infection and 13 healthy infants. Interferon-gamma responses were increased significantly during adenoviral, parainfluenzaviral and the majority of the rhinoviral infections, but remained low during RSV and severe rhinoviral infection. Low interferon-gamma responses were associated with a more severe clinical course of LRTI. This indicates that depending on the nature of the viral pathogen, respiratory virus infections in infants differ significantly with regard to the quantity of the interferon-gamma production and that this may contribute to the clinical course of the disease.
Asunto(s)
Interferón gamma/inmunología , Infecciones por Virus ARN/inmunología , Infecciones del Sistema Respiratorio/inmunología , Infecciones por Adenoviridae/complicaciones , Infecciones por Adenoviridae/inmunología , Bronquiolitis/complicaciones , Bronquiolitis/inmunología , Humanos , Lactante , Leucocitos Mononucleares/inmunología , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/inmunología , Infecciones por Picornaviridae/complicaciones , Infecciones por Picornaviridae/inmunología , Infecciones por Virus ARN/complicaciones , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones del Sistema Respiratorio/complicaciones , Rhinovirus/inmunología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Seven male patients in the David T Purtilo International X-linked Lymphoproliferative Disease (XLP) Registry have undergone allogeneic hematopoietic stem cell transplantation (HSCT). All patients received HSCT from HLA-identical donors: sibling BM, five; unrelated BM, one; and sibling umbilical cord blood, one. Ages at time of HSCT ranged from 5 to 30 years. Pre-HSCT clinical course varied, but four boys had a significant history of chronic and/or serious infections. Conditioning regimens varied: TBI containing regimens, four, chemotherapy only, three. All patients engrafted. Six developed grade I-II acute GVHD but no chronic GVHD. Four are alive and well with normal immune function greater than 3 years following HSCT. Three died within 100 days: disseminated adenovirus, one; polymicrobial sepsis, one; and multiple organ system failure and bleeding diathesis, one. No EBV-associated post-transplant complications were observed, even though all donors except the umbilical cord blood were EBV-seropositive. Unsuccessful HSCT was associated with age at HSCT (> 15 years), TBI-containing regimen and significant history for pre-HSCT infections. These results provide evidence that HSCT performed during childhood with HLA-identical sibling donors, regardless of EBV serostatus, offers the only curative therapy for XLP.
Asunto(s)
Ligamiento Genético , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/terapia , Cromosoma X/genética , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Niño , Preescolar , Femenino , Sangre Fetal/citología , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/inmunología , Humanos , Donadores Vivos , Trastornos Linfoproliferativos/inmunología , Masculino , Sistema de Registros , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
We report a 5.9-year-old boy with X-linked lymphoproliferative syndrome (XLP) who presented with acute severe infectious mononucleosis. Clinical symptoms rapidly improved after chemotherapy with etoposide. Allogeneic bone marrow transplantation (BMT) was performed after conditioning with etoposide, busulfan and cyclophosphamide. After successful hematopoietic recovery we were able to demonstrate seroconversion from an impaired antibody response to Epstein-Barr virus (EBV) to a normal antibody-producing state in an immunocompetent child. The only post-transplant complication was mild acute graft-versus-host disease (GVHD). Three years after BMT, the boy is healthy and shows no signs of immunodeficiency. This is the first report on successful allogeneic BMT in the severe course of acute infectious mononucleosis in a patient with XLP. We speculate that the application of etoposide contributed to the positive outcome in this patient.
Asunto(s)
Trasplante de Médula Ósea , Ligamiento Genético , Mononucleosis Infecciosa/terapia , Trastornos Linfoproliferativos/terapia , Cromosoma X , Enfermedad Aguda , Preescolar , Etopósido/uso terapéutico , Humanos , Trastornos Linfoproliferativos/genética , Masculino , Trasplante HomólogoRESUMEN
Invasive fungal infections, mostly caused by Candida and Aspergillus species, are a major cause of early morbidity and mortality in immunocompromised children. The treatment of choice for systemic fungal infections is still the early intravenous administration of amphotericin B. However, conventional AMB therapy is often limited by severe side effects such as fever, chills, bronchospasm, and nephrotoxicity. In recent reports liposomal AMB (AmBisome) was shown to be effective in the treatment of severe systemic fungal infections. So far, clinical experience with AmBisome in children is still anecdotal and no comparative study is yet available. In the following we report on 11 immunosuppressed children who were treated with conventional or liposomal AMB for longer than 3 weeks.
Asunto(s)
Anfotericina B/administración & dosificación , Huésped Inmunocomprometido , Liposomas , Micosis/tratamiento farmacológico , Adolescente , Anfotericina B/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Portadores de Fármacos , Humanos , Lactante , Micosis/etiología , Neoplasias/complicaciones , Neoplasias/terapiaRESUMEN
We report on three children aged 1 1/2, 2 and 9 1/2 years with Wilms' tumor, who developed a tender hepatomegaly and ascites associated with elevated liver enzymes, anemia and thrombocytopenia during chemotherapy. This clinical picture and liver sonography abnormality are best explained by veno-occlusive disease (VOD) of the liver, while other causes of liver disease could not be identified. Actinomycin D dosage was 0.045 mg/kg as bolus injection in two patients and 0.075 mg/kg split over five days in a third patient. Presumable, this drug was the causative agent. VOD was observed after preoperative and postoperative chemotherapy. No child had received abdominal irradiation. The authors comment on the influence of Actinomycin D as the cause for this unusual liver toxicity.