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1.
Stem Cell Res ; 14(2): 198-210, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25679997

RESUMO

Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Adolescente , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Criança , Pré-Escolar , Citogenética/métodos , Feminino , Humanos , Técnicas In Vitro , Lactente , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Síndromes Mielodisplásicas/metabolismo , Transcriptoma
2.
Bone Marrow Transplant ; 50(4): 536-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25621802

RESUMO

Major ABO incompatible BM transplantation carries a risk of acute haemolysis. Red cell depletion reduces this risk but not all incompatible RBC (iRBCs) are removed and in children the residual volume can be significant relative to body weight. We sought to determine the volume of iRBCs that can be safely given to children. All patients receiving fresh BM from a donor with a major ABO blood group mismatch between January 2000 and July 2013 at the Hospital for Sick Children, Toronto, were included. Seventy-eight patients were identified. The median volume of iRBCs transfused was 1.6 mL/kg (range 0.1-10.6 mL/kg). Thirty-five patients had minor haemolytic events and five patients had clinically significant adverse events. Two patients, who received 3.66 and 3.9 mL iRBCs/kg, developed renal impairment and in one case hypoxia and hyperbilirubinaemia. One patient had mild hypotension that resolved with i.v. fluid. Two patients developed hypotension secondary to sepsis and unrelated to BM infusion. Although signs of haemolysis occur, with appropriate hydration and monitoring of renal function, clinically significant adverse events related to the infusion of ABO incompatible BM are rare, and, in this study, were only seen in patients receiving >3 mL/kg of iRBCs per kg.


Assuntos
Sistema ABO de Grupos Sanguíneos , Transplante de Medula Óssea , Transfusão de Eritrócitos , Eritrócitos , Doadores de Tecidos , Adolescente , Criança , Pré-Escolar , Feminino , Hemólise , Humanos , Lactente , Masculino
3.
Pediatr Blood Cancer ; 61(9): 1707-10, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24648289

RESUMO

Several studies in adults have shown patient reported outcomes (PROs) to be effective in enhancing patient-physician communication and discussion of Health Related Quality of Life outcomes. Although less studied, positive results have been demonstrated in children. A PRO-intervention needs to be feasible in clinical practice to be successful. In the current study, 74 parents of children who successfully completed their cancer treatment and 21 pediatric oncologists (POs) evaluated a PRO-intervention and gave recommendations for future use in their practice. Most parents and POs suggested PROs to be an important part of standard care, starting during treatment, with an assessment frequency of every 3 months.


Assuntos
Oncologia , Pais/psicologia , Avaliação de Resultados da Assistência ao Paciente , Médicos/psicologia , Padrões de Prática Médica , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Assistência ao Paciente , Prognóstico , Qualidade de Vida
4.
Psychooncology ; 21(2): 168-75, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22271537

RESUMO

UNLABELLED: Hematopoietic stem cell transplantation is an effective therapy for life-threatening hematological diseases. Parents may be asked to donate hematopoietic stem cells for their child when no compatible related or unrelated donor is available. OBJECTIVE: Parents donating G-CSF mobilized peripheral blood stem cells simultaneously and uniquely fulfill the dual role of donor and caregiver for their ill child. The experiences of both sibling and unrelated stem cell donors have been extensively reported but not those of parental donors. METHODS: We therefore undertook a study specifically to investigate the experiences and coping strategies of parental stem cell donors. In-depth qualitative interviews were conducted with 13 parental donors, which were subsequently transcribed and subjected to thematic analysis. In addition, parental coping was assessed utilizing the Utrecht Coping List. RESULTS: Qualitative analyses revealed four main thematic categories describing the way parental stem cell donation was experienced, namely 'Hope and Fear', 'Need for Information', 'Do Anything for your Child' and 'Transplant Outcome' In addition parents noted similar difficulties which were unrelated to their specific role as a donor, for example they felt socially isolated. CONCLUSIONS: Individual information for the parents needs to address not only the transplantation procedure but particularly those aspects related to the donation process. We feel there is a need for a protocol specifically designed to support and coach parental donors.


Assuntos
Cuidadores/psicologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Pais/psicologia , Doadores de Tecidos/psicologia , Adaptação Psicológica , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Haplótipos , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospitais de Ensino , Humanos , Lactente , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Neoplasias/cirurgia , Países Baixos , Pesquisa Qualitativa , Fatores Socioeconômicos , Transplante Homólogo
5.
Bone Marrow Transplant ; 47(3): 360-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21892212

RESUMO

Anti-thymocyte globulin (ATG), raised in rabbits, is frequently used in allogeneic hematopoietic SCT (HSCT), to prevent graft rejection and acute GVHD. In solid organ transplant patients, antibodies to rabbit IgG result in an enhanced clearance of ATG. The occurrence of such antibodies in HSCT recipients and their clinical impact is unknown. Concentrations of ATG and anti-ATG antibodies were measured in 72 pediatric HSCT recipients treated with ATG as part of the conditioning. Anti-ATG antibodies were detected in 20 children (28%), all transplanted with a non-depleted graft. IgG anti-ATG, alone or combined with IgM and/or IgA anti-ATG, appeared in 10 children. Four patients developed IgG anti-ATG antibodies early (before day 22) post-HSCT. They had steep drops in ATG levels and showed rapid T-cell recovery, which was associated with a significantly increased risk of acute GVHD. In six patients IgG anti-ATG responses occurred later (range 28-46 days) after HSCT without an increased risk of GVHD. A total of 10 children only mounted an IgM (and IgA) anti-ATG response, which was without major impact on ATG levels. These results indicate that early development of IgG anti-ATG antibodies has a major impact on acute GVHD. Routine analysis ATG/anti-ATG Ab measurement should be considered.


Assuntos
Soro Antilinfocitário/química , Doença Enxerto-Hospedeiro/diagnóstico , Imunoglobulina G/química , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Anticorpos/química , Soro Antilinfocitário/imunologia , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunoglobulina A/química , Imunoglobulina M/química , Lactente , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Bone Marrow Transplant ; 47(5): 677-83, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21860428

RESUMO

To investigate whether all patients in need of an allogeneic hematopoietic SCT (HSCT) are offered one, we retrospectively investigated the policy for all children diagnosed with myelodysplastic syndrome (n=90) or relapsed AML (n=75) between 1998 and 2008. These children are registered at diagnosis and treated according to protocols of the Dutch Childhood Oncology Group, which provides accurate disease incidence data and protocol-indicated appropriateness for HSCT. For 48 (30%) patients, a family donor was identified; for 90 (57%) patients, an unrelated donor (UD) search was performed; and for 21 (13%) patients, no UD search was initiated. Reasons for not initiating an UD search include: progressive disease (n=10), conserve quality of life (n=1), stable disease (n=3), immunosuppressive therapy (n=2), patient death (n=3), patient lives abroad (n=1) and second relapse (n=1). On the basis of the time interval between date of diagnosis and date of death/last follow-up, for eight (5%) patients, it may be questioned why an UD search was not performed. The fact that 95% of all children are given the option of an allogeneic HSCT is encouraging and reasons not to transplant seem fair in most cases.


Assuntos
Acessibilidade aos Serviços de Saúde , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Países Baixos , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Doadores não Relacionados
7.
Bone Marrow Transplant ; 46(2): 200-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20400983

RESUMO

When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Doença Aguda , Adolescente , Antígenos CD34/sangue , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Rejeição de Enxerto , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Risco , Transplante Homólogo
8.
Leukemia ; 24(8): 1462-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20535148

RESUMO

Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level >or=1 x 10(-4) were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n=1-4). The intervention was associated with graft versus host disease >or=grade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0-30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Risco
9.
Bone Marrow Transplant ; 45(6): 1102-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19881554

RESUMO

With the aim of assessing parental stress after SCT, 73 parents of children and adolescents who underwent SCT 5 or 10 years ago responded to questionnaires on general distress (General Health Questionnaire (GHQ)), disease-related stress (Pediatric Inventory for Parents-short form (PIP-SF)) and perceptions of child vulnerability (Child Vulnerability Scale (CVS)). General distress scores were comparable with the reference groups, but 40% of the mothers at 5 years after SCT reported increased stress levels as compared with 26% in the community-based reference group. Disease-related stress was comparable with the reference group of parents of children who were just off cancer treatment, 5 years after SCT. At 10 years after SCT, scores were lower than the reference group. Perceived child vulnerability did diminish over time, but remained high in parents of SCT survivors, compared with parents of healthy children: 96% of the parents at 5 years after SCT and 76% of the parents at 10 years after SCT scored above the cutoff point. Perceived vulnerability was found to be a predictor for parental disease-related stress. To conclude, although most parents of SCT survivors are resilient, the majority of parents perceive their child to be much more vulnerable as compared with parents of healthy children. This perception is associated with disease-related stress and may induce overprotective parenting.


Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Pais/psicologia , Estresse Psicológico , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Relações Pais-Filho , Poder Familiar , Valor Preditivo dos Testes , Inquéritos e Questionários , Sobreviventes
10.
Bone Marrow Transplant ; 45(6): 1056-61, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19881556

RESUMO

CsA is commonly used after haematological SCT (HSCT) as GVHD prophylaxis. In solid organ transplantation, area under the blood concentration vs time curve (AUC) correlates with clinical outcome. However, in HSCT, it has not been determined whether the AUC is superior to trough level monitoring to optimize clinical efficacy of CsA therapy. Therefore, the aim of this study was to investigate the relationships between CsA trough levels and/or AUC early after HSCT with clinical outcome. A total of 91 children (1.1-17.3 years) were treated consecutively with HSCT for a haematological malignancy. CsA trough levels were obtained and were used to estimate the AUC, retrospectively, with a NONMEM (Non-Linear Mixed Effects Modelling) method. Subsequently, these exposure parameters were correlated to the occurrence of acute GVHD, relapse risk (RR) and OS. Low CsA trough levels were found to correlate with the occurrence of acute GVHD. In addition, a CsA AUC over 3000 mcg h/l in AML patients was associated with a higher RR and a reduced OS. This was not the case for ALL patients. Thus, monitoring CsA exposure early after HSCT and adjusting the CsA dose to a predefined target trough level and AUC may provide a tool to influence GVHD/GVL balance.


Assuntos
Ciclosporina/farmacocinética , Doença Enxerto-Hospedeiro/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Aguda , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunossupressores/farmacocinética , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
Bone Marrow Transplant ; 45(1): 79-85, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19421172

RESUMO

The aim of our study was to assess the cumulative incidence and severity ('burden') of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors, at least 2 years after transplantation. The presence and severity of late effects in each survivor was documented according to the Common Terminology Criteria for Adverse Events (version 3.0). The burden of late effects was graded from mild to disabling/life-threatening. Risk factors for a high burden of late effects were assessed by univariate and multivariate logistic regression analyses. Among 162 survivors of HSCT seen in our late effects outpatient clinic, cumulative incidence of late effects was 93.2% after a median follow-up time of 7.2 years (range 2.0-21.0 years) after HSCT. The burden of late effects was mild, moderate, severe and disabling in 28, 41, 24 and 1% of survivors respectively. Risk factors for a severe or disabling burden of late effects were older age at HSCT (P for trend <0.001) and a conditioning regimen including irradiation OR 2.2, 95% CI 1.1-4.7, P=0.03). In conclusion, a high burden of late effects is found in childhood HSCT survivors after a median follow-up of only 7 years.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Doenças do Sistema Endócrino/etiologia , Feminino , Humanos , Lactente , Masculino , Qualidade de Vida , Fatores de Risco , Sobreviventes , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversos
12.
Bone Marrow Transplant ; 45(1): 87-95, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19448680

RESUMO

The transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic T-lymphocyte precursor (CTLp)-negative donors and (2) protective isolation of the recipient and antimicrobial suppression of his/her gut microflora to prevent infections and acute GVHD. Engraftment, GVHD, relapse in the case of malignancy and survival were studied retrospectively in 126 evaluable children, transplanted between 1988 and 2005. In addition to the effect of HLA-matching, that of other transplant-relevant variables on the outcome was also studied. Actuarial OS was 65% and the EFS was 59%, 13% graft failures occurred and 7.5% > or =grade II acute GVHD. HLA-class II mismatches combined with HLA-class I matches resulted in a superior OS of 92%, as did a negative vs positive CTLp test, that is, 65 vs 33%. Analysis of other variables showed a poorer OS in patients > or =10 yrs vs <10 yrs, that is, 54 vs 73%, and in male recipients of a female donor graft, that is, 53 vs 69% for other combinations. UD-BMT can be optimized by permitting HLA-class I-matched and/or CTLp-negative donors, and probably by choosing male donors for male recipients.


Assuntos
Transplante de Medula Óssea/métodos , Política de Saúde , Adolescente , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/imunologia , Países Baixos/epidemiologia , Isolamento de Pacientes , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
14.
Br J Cancer ; 101(11): 1909-18, 2009 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-19888226

RESUMO

BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumour in children and young adults, with poor survival in 40% of patients. To identify the signalling pathways involved in tumourigenesis, we compared gene expression in osteosarcoma with that in its presumed normal counterparts. METHODS: Genome-wide expression profiles were generated from 25 high-grade central osteosarcoma prechemotherapy biopsies, 5 osteoblastomas, 5 mesenchymal stem cell (MSC) populations and these same MSCs differentiated into osteoblasts. Genes that were differentially expressed were analysed in the context of the pathways in which they function using the GenMAPP programme. RESULTS: MSCs, osteoblasts, osteoblastomas and osteosarcomas clustered separately and thousands of differentially expressed genes were identified. The most significantly altered pathways are involved in cell cycle regulation and DNA replication. Several upstream components of the Wnt signalling pathway are downregulated in osteosarcoma. Two genes involved in degradation of beta-catenin protein, the key effectors of Wnt signalling, Axin and GSK3-beta, show decreased expression, suggesting that Wnt signalling is no longer under the control of regular signals. Comparing benign osteoblastomas with osteosarcomas identified cell cycle regulation as the most prominently changed pathway. CONCLUSION: These results show that upregulation of the cell cycle and downregulation of Wnt signalling have an important role in osteosarcoma genesis. Gene expression differences between highly malignant osteosarcoma and benign osteoblastoma involve cell cycle regulation.


Assuntos
Neoplasias Ósseas/patologia , Células-Tronco Mesenquimais/patologia , Células-Tronco Neoplásicas/patologia , Osteossarcoma/patologia , Adolescente , Adulto , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Ciclo Celular/fisiologia , Diferenciação Celular , Linhagem Celular Tumoral , Criança , Pré-Escolar , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Osteoblastoma/genética , Osteoblastoma/metabolismo , Osteoblastoma/patologia , Osteossarcoma/genética , Osteossarcoma/metabolismo , Transdução de Sinais , Regulação para Cima , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Adulto Jovem
15.
Support Care Cancer ; 17(12): 1435-43, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19572154

RESUMO

GOALS OF WORK: Pediatric stem cell transplantation (SCT) is a stressful treatment for children with relapsed or high-risk malignancies, immune deficiencies and certain blood diseases. Parents of children undergoing SCT can experience ongoing stress related to the SCT period. The aim of this article was to present a literature review of articles on parental distress and adaptation before, during, and after SCT and to identify risk and protective factors. MATERIALS AND METHODS: The review was conducted systematically by using PubMed, Web of Science, PsychInfo, and Picarta databases. Eighteen articles met our inclusion criteria: publishing date between January 1, 1990 and January 1, 2009; studies concerning parents of children undergoing SCT; studies examining the psychological adjustment and/or stress reactions of parents as primary outcomes and studies available in English. MAIN RESULTS: Highest levels of parental stress are reported in the period preceding SCT and during the acute phase. Stress levels decrease steadily after discharge in most parents. However, in a subgroup of parents, stress levels still remain elevated post-SCT. Parents most at risk in the longer term display highest levels of stress during the acute phase of the SCT. CONCLUSIONS: Psychosocial assessment before SCT, during the acute phase and in the longer term, is necessary to identify parents in need for support and follow-up care.


Assuntos
Pais/psicologia , Transplante de Células-Tronco/psicologia , Estresse Psicológico/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Alta do Paciente , Fatores de Risco , Transplante de Células-Tronco/métodos , Fatores de Tempo
16.
Bone Marrow Transplant ; 42 Suppl 2: S60-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18978747

RESUMO

Mesenchymal stromal cells (MSCs) can be isolated from several human tissues and expanded for clinical use. MSCs are identified by phenotypic and functional characteristics, and are poor Ag-presenting cells not expressing MHC class II or co-stimulatory molecules. MSCs have potent immune-modulatory effects and in vitro induce a more anti-inflammatory or tolerant phenotype. Clinical studies have exploited both the immune-modulatory properties of MSCs as well as their hematopoietic supportive role. MSCs have been safely administered for the treatment of severe steroid refractory GVHD. A phase I/II multicenter study included 25 children in whom 80% responded to either one or two infusions of MSCs derived mainly from third party donors. Twenty children have undergone co-transplantation of haploidentical MSCs with PBSC in a phase I/II study, which has overcome the problems of graft failure in HLA-disparate grafts. Similarly, co-transplantation of MSCs and cord blood stem cells is under investigation. MSCs may have important future potential for the treatment of pediatric autoimmune disease as well as inborn errors such as osteogenesis imperfecta. Currently, much needed randomized studies under the auspices of the EBMT are ongoing to determine the optimal use of these exciting new modalities of treatment.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Neoplasias/terapia , Células Estromais/transplante , Tolerância ao Transplante , Adulto , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Hematopoese/imunologia , Humanos , Masculino , Neoplasias/imunologia , Osteogênese Imperfeita/imunologia , Osteogênese Imperfeita/terapia , Células Estromais/imunologia , Transplante Homólogo
17.
Bone Marrow Transplant ; 41 Suppl 2: S58-64, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18545246

RESUMO

Allogeneic hematopoietic SCT (HSCT) is an established treatment for some children with life-threatening hematological disease, immune deficiencies and inborn errors of metabolism. Despite advances in prevention and post transplant immuno-suppressive strategies, acute GvHD (aGvHD) remains a major cause of morbidity and mortality in children undergoing SCT. Although reported incidence rates differ, it has been estimated that, depending upon the patient and donor cohort studied, 20-50% of all transplanted patients will experience grade 2 or more aGvHD despite immuno-suppressive prophylaxis. aGvHD occurs when transplanted donor T lymphocytes recognize antigenic disparities between the host and recipient. Pathways other than direct T-cell-mediated cytotoxicity have been shown to be important in the pathogenesis. Inflammatory cytokine release has been implicated as the primary mediator of aGvHD and activation of T cells is one step in the complex process. Deregulated cytokine release by cells other than T cells leads to tissue damage associated with aGvHD. GvHD is a factor that compromises the overall success rate of allogeneic HSCT and remains a challenge, which, in turn, requires an understanding of the pathophysiology, clinical presentation and management of this complication. The authors concentrate on the most recent knowledge of the pathogenesis as well as the classification of aGvHD.


Assuntos
Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Predisposição Genética para Doença/genética , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunidade Celular/imunologia , Polimorfismo de Nucleotídeo Único/genética , Transplante Homólogo
18.
Pediatr Blood Cancer ; 50(5): 1062-4, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18085691

RESUMO

In 4-6% of patients with renal tumors in children intravascular infiltration is found. Tumor emboli are even rarer, and sudden death as presenting symptom has only been described at presentation in Wilms tumor (WT) in six cases so far. This report describes two recent cases of sudden death in patients with renal tumors in which a fatal pulmonary embolus was the first presentation.


Assuntos
Morte Súbita/etiologia , Neoplasias Renais/complicações , Embolia Pulmonar/complicações , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Embolia Pulmonar/patologia
19.
Bone Marrow Transplant ; 40(4): 319-27, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17572715

RESUMO

To examine relapse, survival and transplant-related complications in relationship to disease- and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n=24), ALL in second remission (n=53) and AML in first remission (n=55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n=24), later short-course MTX and CsA (n=102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II-IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P=0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P=0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irradiação Corporal Total/métodos , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
20.
J Pathol ; 212(2): 188-97, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17447723

RESUMO

Langerhans cell histiocytosis (LCH) is a disease characterized by an uncontrolled clonal proliferation of Langerhans cells, whose aetiology is still unclear. The clonal nature of LCH could support the hypothesis that it is a neoplastic disease with unlimited growth potential. One requirement for unlimited proliferation is the maintenance of telomere length. In a group of 70 patients, we set out to investigate whether a telomere maintenance mechanism is indeed active in LCH cells. This work showed that LCH cells from all restricted skin LCH lesions (6/6) expressed telomerase as assessed by human telomere reverse transcriptase (hTERT) immunohistochemistry, whereas LCH cells from the majority of the bone lesions analysed did not express hTERT (26/34). Interestingly, in contrast to the solitary bone lesions, LCH cells from lesions of multi-system patients always expressed telomerase (11/11), regardless of the lesional site. In situ telomeric repeat amplification protocol (TRAP) assays performed on different lesional sites showed that this telomerase was active. In addition, the telomere length of LCH cells from a hTERT-positive skin multi-system lesion was long and homogeneous when compared to that in the LCH cells from hTERT-negative bone single-system LCH lesions, which was heterogeneous in length. No evidence for an alternative lengthening of telomeres mechanism was found in hTERT-negative lesions. The difference in telomerase expression and telomere length at the different lesional sites and in biopsies from patients with solitary versus multi-system disease appears to reflect the diverse clinical presentation and course of this disease. The results from this study have important implications for understanding the nature of this disease.


Assuntos
Antígenos CD1/imunologia , Histiocitose de Células de Langerhans/enzimologia , Telomerase/análise , Osso e Ossos/imunologia , Osso e Ossos/patologia , Criança , Células Gigantes/metabolismo , Células Gigantes/patologia , Histiocitose de Células de Langerhans/imunologia , Humanos , Imuno-Histoquímica/métodos , Células de Langerhans/enzimologia , Células de Langerhans/imunologia , Pele/imunologia , Pele/patologia , Telômero/patologia
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