RESUMEN

Glanzmann thrombasthenia (GT) is a rare, autosomal recessive coagulopathy characterized by either qualitative or quantitative abnormalities of the membrane glycoprotein αIIbß3 complex leading to bleeding tendencies, ranging from purpura to life-threatening hemorrhage. Although patients can be managed with supportive measures including platelet transfusions, complications such as alloimmunization are possible. Allogeneic stem cell transplantation (ASCT) can be indicated in severe cases of GT. We report the case of an eight-month-old girl diagnosed with moderate-severe GT, who was successfully treated with a reduced-intensity, human leukocyte antigen (HLA)-identical ASCT.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Trombastenia/terapia , Plaquetas/inmunología , Plaquetas/metabolismo , Femenino , Antígenos HLA/genética , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad , Humanos , Lactante , Índice de Severidad de la Enfermedad , Hermanos , Trombastenia/diagnóstico , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

BACKGROUND: Studies comparing survival of adolescent and young adult (AYA) patients to that of younger patients with newly diagnosed acute myeloid leukemia (AML) have yielded conflicting results. In order to more accurately characterize relative survival and other outcomes of AYA patients, a cross-study analysis was conducted using data from recent trials conducted by the Children's Cancer Group (CCG) and Children's Oncology Group (COG). METHODS: Data were combined from the CCG-2891, CCG-2941, CCG-2961, and AAML03P1 trials. The data set included 1840 patients, comprising 238 AYA and 1602 younger patients. RESULTS: Overall survival was not significantly different in the 2 groups (AYA, 49% ± 7% versus younger, 54% ± 3% (± 2 standard errors), P = .058). Relapse was lower in AYA patients (30% ± 7% versus 41% ± 3%, P = .002), but treatment-related mortality (TRM) was higher (25% ± 6% versus 12% ± 2%, P < .001). After adjustment for other factors, older age remained strongly associated with TRM (hazard ratio = 2.30, 95% CI = 1.59-3.33, P < .001). Infection accounted for the excess TRM in AYA patients. CONCLUSIONS: Survival in AYA and younger patients with newly diagnosed AML is similar; however, older patients are at higher risk for TRM. More effective strategies for preventing mortality from infection in AYA patients are needed.

Asunto(s)

Leucemia Mieloide Aguda/mortalidad , Adolescente , Factores de Edad , Niño , Femenino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Adulto Joven

RESUMEN

Children who receive head, neck, or chest radiotherapy for various primary malignancies have increased risk for secondary thyroid malignancy. Thyroid nodules are difficult to identify by physical examination and/or laboratory tests. Thyroid ultrasound can detect non-palpable nodules without adverse side effects. We performed a retrospective chart review of 36 patients who received radiotherapy and underwent thyroid ultrasound. Forty-seven percent (n = 17) had ≥1 nodule(s) detected. Seven patients underwent thyroidectomy; four of whom were diagnosed with thyroid malignancy. Our study suggests routine use of thyroid ultrasound in high-risk patients detects subclinical thyroid nodules and potential thyroid malignancy post-radiotherapy.

Asunto(s)

Irradiación Craneana/efectos adversos , Cuello/efectos de la radiación , Neoplasias Primarias Secundarias/diagnóstico por imagen , Tórax/efectos de la radiación , Glándula Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/diagnóstico por imagen , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias Primarias Secundarias/etiología , Estudios Retrospectivos , Neoplasias de la Tiroides/etiología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/etiología , Ultrasonografía

RESUMEN

PURPOSE: Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high-risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival (OS) rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin (IL)-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression. EXPERIMENTAL DESIGN: DNA samples from 96 high-risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor, rs1800795 and rs8192284, respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was done to determine SNP-related event-free survival (EFS) and OS rates. RESULTS: The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in high-risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value. CONCLUSIONS: The rs1800795 SNP [-174 IL-6 (G > C)] represents a novel and independent prognostic marker for both EFS and OS in high-risk neuroblastoma. Because the rs1800795 SNP [-174 IL-6 (G > C)] has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma.

Asunto(s)

Interleucina-6/genética , Neoplasias del Sistema Nervioso/diagnóstico , Neuroblastoma/diagnóstico , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-6/genética , Biomarcadores de Tumor/genética , Preescolar , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Neoplasias del Sistema Nervioso/genética , Neoplasias del Sistema Nervioso/mortalidad , Neuroblastoma/genética , Neuroblastoma/mortalidad , Polimorfismo de Nucleótido Simple/fisiología , Valor Predictivo de las Pruebas , Pronóstico , Regiones Promotoras Genéticas/genética , Factores de Riesgo , Análisis de Supervivencia

RESUMEN

Fibrinogen is an essential component of the coagulation cascade and the acute phase response. The native 340 kDa molecule has a symmetrical trinodular structure composed of a central E-domain connected to outer D-domains by triple helical coiled-coils.1 Several mutations known to cause hypofibrinogenemia occur within the C-terminal gammaD-domain and have helped to elucidate the structurally and functionally important areas of this domain.2-5 Here we report the identification of a novel point mutation gammaG200V (fibrinogen Columbus) causing hypofibrinogenemia and co-segregating with three genetic thrombophilia risk factors.

Asunto(s)

Resistencia a la Proteína C Activada/genética , Afibrinogenemia/genética , Sustitución de Aminoácidos , Fibrinógenos Anormales/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Mutación Missense , Mutación Puntual , Trombofilia/genética , Resistencia a la Proteína C Activada/complicaciones , Adulto , Afibrinogenemia/complicaciones , Hemorragia Cerebral/etiología , Preescolar , Enfermedades en Gemelos , Factor V/genética , Femenino , Fibrinógenos Anormales/química , Genotipo , Humanos , Recién Nacido , Masculino , Modelos Moleculares , Linaje , Conformación Proteica , Estructura Terciaria de Proteína , Factores de Riesgo , Relación Estructura-Actividad , Trombofilia/complicaciones