RESUMO
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.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Repetições de Microssatélites , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Humanos , Análise de Sobrevida , Resultado do TratamentoRESUMO
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.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Genótipo , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/terapia , Humanos , Lactente , Radiografia Torácica , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/economia , Estudos Retrospectivos , Ribavirina/economia , Ribavirina/uso terapêutico , Taxa de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
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.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Ensaios Clínicos como Assunto/métodos , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Valor Preditivo dos Testes , Prognóstico , Recidiva , Medição de Risco/métodosRESUMO
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.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , RNA Neoplásico/metabolismo , Receptores de Estrogênio/metabolismo , Receptores da Prolactina/genética , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , RNA Mensageiro/metabolismo , Receptores de Progesterona/metabolismo , Saúde da MulherRESUMO
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.
Assuntos
Neuroblastoma/terapia , Seguimentos , Humanos , Recém-Nascido , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/mortalidade , Prognóstico , Sistema de Registros , Taxa de Sobrevida , Resultado do Tratamento , Ultrassonografia Pré-Natal , Reino Unido/epidemiologiaRESUMO
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.
Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Diagnóstico por Imagem , Melanoma/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Osteossarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Criança , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Segunda Neoplasia Primária/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Retinoblastoma/patologia , Retinoblastoma/terapia , Fatores de RiscoRESUMO
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.
Assuntos
Segunda Neoplasia Primária/etiologia , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/etiologia , Neoplasias do Sistema Nervoso Central/etiologia , Criança , Feminino , Predisposição Genética para Doença , Doença de Hodgkin/terapia , Humanos , Masculino , Melanoma/etiologia , Neoplasias Induzidas por Radiação , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/genética , Osteossarcoma/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Radioterapia/efeitos adversos , Neoplasias da Retina/genética , Neoplasias da Retina/terapia , Retinoblastoma/genética , Retinoblastoma/terapia , Fatores de Risco , Neoplasias da Glândula Tireoide/etiologiaAssuntos
Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Testes de Coagulação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Antígenos de Histocompatibilidade Classe I , Teste de Histocompatibilidade , Leucemia-Linfoma Linfoblástico de Células Precursoras , Transplante de Células-Tronco , Doadores não Relacionados , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoAssuntos
Rearranjo Gênico do Linfócito T/genética , Leucemia Linfoide/diagnóstico , Neoplasia Residual/diagnóstico , Reação em Cadeia da Polimerase/efeitos dos fármacos , Reação em Cadeia da Polimerase/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Soroalbumina Bovina/metabolismo , Doença Aguda , Animais , Bovinos , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Diagnóstico Diferencial , Genes de Imunoglobulinas/genética , Genes Codificadores dos Receptores de Linfócitos T/genética , Humanos , Leucemia Linfoide/genética , Leucemia Linfoide/imunologia , Neoplasia Residual/genética , Neoplasia Residual/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Soroalbumina Bovina/genéticaAssuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Acidente Vascular Cerebral/induzido quimicamente , Adolescente , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Feminino , Humanos , Injeções Espinhais , Masculino , Metotrexato/uso terapêutico , Reino UnidoAssuntos
Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Stenotrophomonas maltophilia/isolamento & purificação , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/etiologia , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/etiologia , Doenças Hematológicas/complicações , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Antígenos CD34/sangue , Osteopetrose/fisiopatologia , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco , Criança , Pré-Escolar , Ensaio de Unidades Formadoras de Colônias , Feminino , Humanos , Lactente , Recém-Nascido , Contagem de Leucócitos , Masculino , Osteopetrose/terapia , Transplante Autólogo , Transplante HomólogoRESUMO
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.