RESUMEN
Microsatellite analyses show that self-reported ethnicity often correlates poorly with true genetic ancestry. As unknown ancestral differences could potentially have an impact on transplant outcome, we developed an average allele length discrepancy (AALD) score to assess allele length discrepancy between donor/recipient (D/R) using microsatellites analysed routinely in post-transplant chimeric assessment. This was then compared with outcome in a homogeneously treated cohort of pediatric patients undergoing high-resolution sibling or matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL). AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for sibling pairs and 0.8-2.17 (median 1.6) for high-resolution matched unrelated donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score, which reached statistical significance above a threshold of 1.7 for OS. Patients whose transplants had an AALD score of ⩾1.8 had a risk of non-relapse mortality 4.9 times greater (P=0.025) and relapse risk three times greater (P=0.058) than those scoring <1.8. This approach will now be explored in a Centre International for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs across all disease groups; if confirmed, it has the potential to improve donor selection for patients with multiple prospective donors.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Repeticiones de Microsatélite , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante/métodos , Humanos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Respiratory syncytial virus (RSV) is known to cause acute lung injury in the immunocompromised host, especially recipients of bone marrow allografts. Specific prognostic factors for the development of severe life-threatening disease remain to be identified as does the optimum treatment of established disease. Over a 5-year period the incidence and outcome of RSV in BMT recipients was analysed retrospectively. Prognostic factors assessed included type of transplant, engraftment status at the time of infection, the presence of lower respiratory tract disease, viral genotype and treatment received. During the study period, 26 of 336 (6.3%) allogeneic stem-cell recipients were identified as having RSV. Five patients (19.2%) died as a direct result of RSV. One patient died secondary to an intracranial bleed with concomitant RSV. There were four patients with graft failure (two primary and two secondary) attributable to the presence of RSV, two of whom subsequently died of infections related to prolonged myelosuppression. The presence of lower respiratory tract infection and a poor overall outcome was the only statistically significant association. Unrelated donor transplants and AML as the underlying disease appeared to be associated with a poorer outcome. Engraftment status, viral genotype and RSV treatment received did not correlate with outcome. We conclude that future studies are required to identify early sensitive and reproducible prognostic factors of RSV in the immunocompromised host. The roles of intravenous and nebulised ribavirin need to be clarified by prospective controlled trials.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Virus Sincitial Respiratorio/etiología , Adolescente , Adulto , Niño , Preescolar , Genotipo , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas/terapia , Humanos , Lactante , Radiografía Torácica , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/economía , Estudios Retrospectivos , Ribavirina/economía , Ribavirina/uso terapéutico , Tasa de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Risk directed treatment forms a central component of modern protocols for childhood acute lymphoblastic leukaemia (ALL). A review of recent studies of minimal residual disease (MRD) analysis shows that it is a powerful prognostic factor in both first line and relapse treatment. However, the value of MRD analysis is both time point and protocol specific, and the threshold for MRD detection of the technique used impacts upon the results obtained. MRD analysis does have a useful role to play in the risk directed treatment of childhood ALL, and this is currently being investigated in large prospective studies.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Niño , Ensayos Clínicos como Asunto/métodos , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Valor Predictivo de las Pruebas , Pronóstico , Recurrencia , Medición de Riesgo/métodosRESUMEN
AIM: Previous in vitro studies have shown that tamoxifen down-regulates prolactin receptors in breast cancer cells. The aim of this study was to determine whether similar changes might provide the basis for a predictive test in patients. METHODS: Biopsy specimens were obtained from 28 post-menopausal women immediately before initiation of treatment with tamoxifen (20 mg daily) and after treatment for 7 days. Prolactin receptor mRNA, determined by reverse-transcription polymerase chain reaction, was then expressed relative to 18S ribosomal RNA. RESULTS: There was good evidence for a decline in receptor expression in response to treatment with tamoxifen in the whole group (p = 0.036) but with a particularly marked decrease (>60%) in a sub-group of 11 patients. No clear correlation with tumour type or grade, or with several other markers (progesterone receptor, c-erb B-2, pS2, or Bcl-2) was apparent. CONCLUSION: Tamoxifen reduces expression of mRNA encoding the prolactin receptor in a sub-group of breast tumours and might provide the basis for a predictive test for tamoxifen therapy.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , ARN Neoplásico/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Prolactina/genética , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Neoplasias de la Mama/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Posmenopausia/efectos de los fármacos , Posmenopausia/metabolismo , ARN Mensajero/metabolismo , Receptores de Progesterona/metabolismo , Salud de la MujerRESUMEN
Over nine years, 33 children with neonatal neuroblastoma were registered with the UKCCSG (United Kingdom Children's Cancer Study Group). Tumours of all stages were found, but stage 4S disease predominated. Five tumours were detected prenatally by ultrasonography. Treatment varied according to tumour stage. The overall survival of the group was 91%. Ten children have had long term complications as a result of their disease, usually as a result of spinal tumour involvement. The good overall prognosis in this age group is encouraging, but the poor neurological outcome of patients with intraspinal extension is of concern.
Asunto(s)
Neuroblastoma/terapia , Estudios de Seguimiento , Humanos , Recién Nacido , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/mortalidad , Pronóstico , Sistema de Registros , Tasa de Supervivencia , Resultado del Tratamiento , Ultrasonografía Prenatal , Reino Unido/epidemiologíaRESUMEN
The aim of this article is to provide an up to date review of second malignant neoplasms (SMN's) following treatment for childhood cancer, referring to their incidence, the role of genetic factors, and how the primary malignancy and treatment received influence the type, site and prognosis of SMN's. The role of genetic factors will be discussed as far as they impact upon a predisposition to later development of SMN's. The primary malignancies that have important associations with SMN's will then be discussed, in particular Hodgkin's disease, retinoblastoma and acute lymphoblastic leukaemia. The important second malignancies will be highlighted, including tumours of the CNS and thyroid, osteosarcoma, secondary acute myeloid leukaemia and melanoma. Emphasis will be put upon identifying which patients are most likely to suffer from these tumours. An important part of the article are case histories. These are provided in combination with illustrations as a useful adjunct to the text, with a particular emphasis on radiological features, diagnosis and screening. Finally, the important but different roles of causal agents, in particular chemotherapy and radiotherapy are highlighted.
Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico , Diagnóstico por Imagen , Melanoma/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Osteosarcoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Niño , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Neoplasias Primarias Secundarias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Retinoblastoma/patología , Retinoblastoma/terapia , Factores de RiesgoRESUMEN
The aim of this article is to provide an up to date review of second malignant neoplasms (SMN's) following treatment for childhood cancer, referring to their incidence, the role of genetic factors, and how the primary malignancy and treatment received influence the type, site and prognosis of SMN's. The role of genetic factors will be discussed as far as they impact upon a predisposition to later development of SMN's. The primary malignancies that have important associations with SMN's will then be discussed, in particular Hodgkin's disease, retinoblastoma and acute lymphoblastic leukaemia. The important second malignancies will be highlighted, including tumours of the CNS and thyroid, osteosarcoma, secondary acute myeloid leukaemia and melanoma. Emphasis will be put upon identifying which patients are most likely to suffer from these tumours. An important part of the article are case histories. These are provided in combination with illustrations as a useful adjunct to the text, with a particular emphasis on radiological features, diagnosis and screening. Finally, the important but different roles of causal agents, in particular chemotherapy and radiotherapy are highlighted.
Asunto(s)
Neoplasias Primarias Secundarias/etiología , Adolescente , Adulto , Antineoplásicos/efectos adversos , Neoplasias Óseas/etiología , Neoplasias del Sistema Nervioso Central/etiología , Niño , Femenino , Predisposición Genética a la Enfermedad , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Melanoma/etiología , Neoplasias Inducidas por Radiación , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/genética , Osteosarcoma/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Radioterapia/efectos adversos , Neoplasias de la Retina/genética , Neoplasias de la Retina/terapia , Retinoblastoma/genética , Retinoblastoma/terapia , Factores de Riesgo , Neoplasias de la Tiroides/etiologíaAsunto(s)
Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anciano , Pruebas de Coagulación Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We present the first detailed study analysing OS in BMT for paediatric ALL following the introduction of high-resolution (HR) HLA matching. A total of 356 consecutive paediatric ALL stem cell transplants performed between 1988 and 2007 were reviewed; 80 of them were performed following the introduction of HR HLA class I and class II matching to the transplant programme in 2002. Comparisons of matched unrelated donor (MUD) transplant outcomes before and after this period were made. Matching at the HR level for HLA-A, -B, -C, -DRB1 and -DQB1 (HR-MUD) correlated with a greater than 25% improvement in 2- and 5-year OS in paediatric ALL patients transplanted with MUDs (P=0.009, P=0.005, respectively). Two-year OS for contemporaneous HLA-matched sibling transplants (80.8%) and HR-MUD transplants (78.8%) was equivalent. At 6%, non-relapse mortality (NRM) in MUD transplants since 2002 was significantly reduced compared with previous epochs. Changes in treatment and epoch-dependent improvements in outcome were reviewed for possible confounders to the influence of HR typing using univariate and multivariate analysis.
Asunto(s)
Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Antígenos de Histocompatibilidad Clase I , Prueba de Histocompatibilidad , Leucemia-Linfoma Linfoblástico de Células Precursoras , Trasplante de Células Madre , Donante no Emparentado , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante HomólogoAsunto(s)
Reordenamiento Génico de Linfocito T/genética , Leucemia Linfoide/diagnóstico , Neoplasia Residual/diagnóstico , Reacción en Cadena de la Polimerasa/efectos de los fármacos , Reacción en Cadena de la Polimerasa/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Albúmina Sérica Bovina/metabolismo , Enfermedad Aguda , Animales , Bovinos , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Diagnóstico Diferencial , Genes de Inmunoglobulinas/genética , Genes Codificadores de los Receptores de Linfocitos T/genética , Humanos , Leucemia Linfoide/genética , Leucemia Linfoide/inmunología , Neoplasia Residual/genética , Neoplasia Residual/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Albúmina Sérica Bovina/genéticaAsunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Metotrexato/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Adolescente , Antimetabolitos Antineoplásicos/uso terapéutico , Niño , Femenino , Humanos , Inyecciones Espinales , Masculino , Metotrexato/uso terapéutico , Reino UnidoAsunto(s)
Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Stenotrophomonas maltophilia/aislamiento & purificación , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Femenino , Infecciones por Bacterias Gramnegativas/etiología , Enfermedades Hematológicas/complicaciones , Humanos , Lactante , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
Autosomal recessive osteopetrosis (OP) is a rare, lethal disorder in which osteoclasts are absent or nonfunctional, resulting in a bone marrow cavity insufficient to support hematopoiesis. Because osteoclasts are derived from hematopoietic precursors, allogeneic hematopoietic cell transplantation can cure the bony manifestations of the disorder. However, high rates of graft failure have been observed in this population. It is not possible to harvest bone marrow from these patients for reinfusion should graft failure be observed. We report that 8 of 10 patients with OP had high numbers of circulating CD34(+) cells (3% +/- 0.9%). This increased proportion of peripheral CD34(+) cells made it possible to harvest 2 x 10(6) CD34(+) cells per kilogram with a total volume of blood ranging from 8.3 to 83.7 mL (1.3-11.6 mL/kg). In addition, colony-forming assays documented significantly more colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid in the blood of osteopetrotic patients compared with controls; the numbers of colony-forming units approximated those found in control marrow. We conclude that OP patients with high levels of circulating CD34(+) are candidates for peripheral blood autologous harvest by limited exchange transfusion. These cells are then available for reinfusion should graft failure be observed in patients for whom retransplantation is impractical.
Asunto(s)
Antígenos CD34/sangre , Osteopetrosis/fisiopatología , Trasplante de Células Madre de Sangre Periférica , Células Madre , Niño , Preescolar , Ensayo de Unidades Formadoras de Colonias , Femenino , Humanos , Lactante , Recién Nacido , Recuento de Leucocitos , Masculino , Osteopetrosis/terapia , Trasplante Autólogo , Trasplante HomólogoRESUMEN
BACKGROUND: Malignant melanoma (MM) is one of the least common types of childhood cancer, accounting for less than 1% of all pediatric malignancies. Neurocutaneous melanosis (NCM) is a rare phakomatosis consisting of congenital abnormal pigmentation of the skin and meninges. The meningeal lesions are particularly prone to malignant change. METHODS: The authors describe 5 patients with NCM and 1 with primary leptomeningeal melanoma (LMM) seen at 2 treatment centers in the north of England over a 13-year period (1984-1997). RESULTS: The clinical features, progress, radiological findings, and treatment of these patients are discussed. All six died within eight months of their diagnosis, illustrating the difficulties faced in treating patients with these conditions. The authors reviewed the published literature on NCM, concentrating on the various therapeutic strategies that have been tried. Very little consistency in approach was found. Malignant skin lesions in NCM may be less responsive than primary malignant melanoma, but the small number of patients with primary LMM or brain metastases of MM make comparisons with NCM difficult. The authors' own series illustrates well the piecemeal nature of therapy for patients with these rare conditions. CONCLUSIONS: The rate of incidence of MM melanoma in the U.K. is increasing, and it will represent an increasing proportion of the pediatric oncologist's workload. A consistent approach to the therapy of patients with metastatic MM and NCM is needed if we are to have any hope of offering more than palliative therapy to these children in the future.