RESUMEN
Thalassemia major and sickle cell disease are the two most widely disseminated hereditary hemoglobinopathies in the world. The outlook for affected individuals has improved in recent years due to advances in medical management in the prevention and treatment of complications. However, hematopoietic stem cell transplantation is still the only available curative option. The use of hematopoietic stem cell transplantation has been increasing, and outcomes today have substantially improved compared with the past three decades. Current experience world-wide is that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80%. However, only a few controlled trials have been reported, and decisions on patient selection for hematopoietic stem cell transplantation and transplant management remain principally dependent on data from retrospective analyses and on the clinical experience of the transplant centers. This consensus document from the European Blood and Marrow Transplantation Inborn Error Working Party and the Paediatric Diseases Working Party aims to report new data and provide consensus-based recommendations on indications for hematopoietic stem cell transplantation and transplant management.
Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Células Madre Hematopoyéticas , Talasemia beta/terapia , Anemia de Células Falciformes/diagnóstico , Niño , Humanos , Talasemia beta/diagnósticoRESUMEN
Sickle cell disease has come to Germany from the Mediterranean region, Africa and the Middle East since the 1950âs and initially mainly concerned paediatricians. Since the 1970âs, the life expectancy of those affected has risen significantly, and about 95â% now live to adulthood. Therefore, general practitioners and internists should be familiar with the different forms of sickle cell disease, especially HbSC disease (approx. 20â%).A precise diagnosis of sickle cell disease (exact phenotype) is essential; the term "sickle cell anaemia" must be avoided. In patients of African origin with microcytosis, slightly elevated reticulocytes and pain symptomatology, the possibility of HbSC disease should be considered - even with age-appropriate haemoglobin values. Annual retinoscopy is recommended for HbSC patients from the age of 7, and for all other sickle cell patients from the age of 10. If a hearing loss occurs in an HbSC patient, phlebotomy should be performed immediately. In all sickle cell patients with dizziness or pain and an Hb >â10âg/dl, phlebotomy is indicated.
Asunto(s)
Anemia de Células Falciformes , Enfermedad de la Hemoglobina SC , África , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/terapia , Hemoglobinas/análisis , Humanos , DolorRESUMEN
We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease.
Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Médula Ósea/efectos adversos , Enfermedades del Sistema Nervioso Central/etiología , Trastornos Gonadales/etiología , Estado de Salud , Enfermedades Pulmonares Obstructivas/etiología , Adolescente , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Enfermedades del Sistema Nervioso Central/fisiopatología , Niño , Selección de Donante , Femenino , Estudios de Seguimiento , Trastornos Gonadales/fisiopatología , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad , Humanos , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Hermanos , Análisis de Supervivencia , Quimera por Trasplante , Resultado del TratamientoRESUMEN
During the past decades sickle cell disease and the thalassemias have come to Northern Europe with migrants from the Mediterranean area and Sub-saharan Africa. There are relatively few sickle cell patients in Germany, Switzerland and Austria compared to our neighbors who had colonies in Africa and most physicians do not treat more than 1-2 patients. Due to progress in prophylaxis and therapy, 85 - 90% of children with sickle cell disease in the USA and Europe reach adult age. With increasing age patients suffer chronic organ damage in addition to episodes of acute organ failure which predominate in childhood. Taking care of sickle cell patients is a challenge and requires a large amount of knowledge and experience. In order to give optimal treatment to our patients we need to make use of the experience and study results of colleagues abroad. In this paper the most important clinical manifestations of the disease are discussed and available information sites are presented.
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/terapia , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/etiología , Adulto , Anemia de Células Falciformes/complicaciones , Humanos , Insuficiencia Multiorgánica/prevención & controlRESUMEN
Familial neuroblastoma is of special interest in view of the oncogenesis of this tumour with its early manifestation in childhood. The inheritance seems to follow an autosomal-dominant mendelian trait with incomplete penetrance. Familial neuroblastomas and ganglioneuromas have not been reported in detail within large treatment studies. A retrospective clinicopathological survey of patients reported to the German neuroblastoma treatment studies over 24 years was performed. Among 2863 patients (2752 neuroblastomas, 111 ganglioneuromas) included in five consecutive trials, only 22 hereditary cases in ten families were observed. Neuroblastomas were found in 18 patients and ganglioneuromas in four, accounting for less than one percent of all cases. Six patients with neuroblastomas had localised disease, seven had stage 4, three had stage 4S, and stage was unknown in two patients. Two families had three affected patients. Contrary to previous reports, age distribution and number of primary tumours in patients with familial data confirm the low prevalence of familial neuroblastoma and may help in counselling the affected families.
Asunto(s)
Ganglioneuroma/genética , Neuroblastoma/genética , Edad de Inicio , Niño , Preescolar , Femenino , Ganglioneuroma/mortalidad , Alemania/epidemiología , Humanos , Lactante , Masculino , Neuroblastoma/mortalidad , Linaje , Prevalencia , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: Little is known about the outcome of pediatric patients with lymphoblastic lymphoma (LBL) who suffer from progressive disease or relapse. PATIENTS AND METHODS: We analyzed the pattern of LBL relapses after current non-Hodgkin's lymphoma Berlin-Frankfurt-Muenster (BFM) frontline therapy between April 1990 and March 2003. Relapse therapy was according to acute lymphoblastic leukemia (ALL) -Relapse-BFM protocols or ALL-BFM protocols for high-risk patients. RESULTS: Twenty-eight (11%) of 251 registered patients with precursor T-cell LBL (T-LBL) and six (8%) of 73 patients with precursor B-cell LBL (pB-LBL) suffered from relapse. Of the 28 patients with T-LBL, one died from infection during relapse chemotherapy, 18 failed to achieve stable remission and died from disease progression, and nine reached allogeneic stem-cell transplantation (SCT). Two of these nine patients who underwent SCT died from transplantation-associated toxicity, three died from disease progression, and four are still alive. These four patients are in second remission of their lymphoma for 48, 68, 125, and 131 months, respectively, after allogeneic SCT. One of the four patients developed colon adenocarcinoma 47 months after SCT. Of the six patients with pB-LBL who experienced relapse, one patient died as a result of toxicity of relapse chemotherapy, two died from disease progression after chemotherapy, and three received allogeneic SCT. Of these, two died from subsequent disease progression, and one is still alive 57 months after allogeneic SCT. CONCLUSION: Using modern conventional therapy in the frontline treatment of LBL, 10% of patients suffer from progressive disease or relapse. Because of the extremely poor reinduction success, the salvage rate for these patients is poor, with only a 14% (SE = 6%) overall survival. Long-term survival was only achieved in those few patients who were able to undergo an allogeneic SCT.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Análisis de Varianza , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Progresión de la Enfermedad , Femenino , Alemania , Humanos , Estimación de Kaplan-Meier , Masculino , Estudios Multicéntricos como Asunto , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Pronóstico , Recurrencia , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/métodos , Suiza , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To improve risk-adapted therapy for localized childhood soft tissue sarcoma within an international multicenter setting. PATIENTS AND METHODS: Four hundred forty-one patients younger than 21 years with localized rhabdomyosarcoma and rhabdomyosarcoma-like tumors (ie, extraosseous tumors of the Ewing family, synovial sarcoma, and undifferentiated sarcoma) were eligible. Therapy was stratified according to postsurgical stage, histology, and tumor site. In unresectable tumors, treatment was further adapted depending on response to induction chemotherapy, TN classification, tumor size and second-look surgery. A novel five-drug combination of etoposide, vincristine, dactinomycin, ifosfamide, and doxorubicin (EVAIA) was evaluated for high-risk patients, but cumulative chemotherapy dosage and treatment duration were reduced for the remaining individuals as compared with that of the previous trial CWS-86. Hyperfractionated accelerated radiotherapy (HART) was recommended at doses of either 32 or 48 Gy. RESULTS: At a median follow-up of 8 years, 5-year event-free survival (EFS) and overall (OS) survival for the entire cohort was 63% +/- 4% and 73% +/- 4%, respectively (all survival rates in this abstract are calculated and displayed with +/-95% CI). EFS/OS rates by histology were 60% +/- 5%/72% +/- 5% in rhabdomyosarcoma, 62% +/- 10%/69% +/- 10% for Ewing tumors of soft tissues, 84% +/- 12%/90% +/- 10% for synovial sarcoma, and 67% +/- 38%/83% +/- 30% for undifferentiated sarcoma, respectively. Response to one cycle of the five-drug combination EVAIA was similar to that of the four-drug combination VAIA used in CWS-86. Two hundred twelve patients with rhabdomyosarcoma underwent radiation (EFS, 66% +/- 6%); 53 of those patients had a favorable risk profile and received 32 Gy of HART (EFS, 73% +/- 12%). TN classification, tumor site, tumor size, histology, and age were prognostic in univariate analysis. CONCLUSION: Improved risk stratification enabled decreased therapy intensity for selected patients without compromising survival. Intensified chemotherapy with EVAIA did not improve outcome of localized high-risk rhabdomyosarcoma.