RESUMO
Malawi launched Option B+, a program for all pregnant or breastfeeding HIV-positive women to begin lifelong combination antiretroviral therapy (cART), in July 2011. This study characterises a portion of the continuum of care within an antenatal setting in Lilongwe. Women testing HIV-positive and having a cART initiation record at Bwaila Antenatal Clinic from July 2013 to January 2014 were included. Using logistic regression models, we analysed relationships between maternal characteristics and return for infant testing. Among 490 HIV-positive women with a cART initiation record, 360 (73%) were retained at three months. Of these, 203 (56%) were adherent. Records of infant testing were located for 204 women (42%). Women who were not retained were less likely to have an early infant diagnosis record (aOR = 0.20; 95% CI: 0.10, 0.41). Among the women retained, there was a non-significant association between maternal adherence and infant testing (OR = 1.35; 95% CI: 0.89, 2.06). Women lost at earlier continuum stages, who are at higher risk for mother-to-child-transmission, were less likely to bring infants for testing. Even with a test-and-treat program, many women did not remain in care or bring their infant for testing. Facilitating strategies to improve these measures remains an important unmet need.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Continuidade da Assistência ao Paciente , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Avaliação de Programas e Projetos de Saúde/métodos , Adulto , Aleitamento Materno , Feminino , Seguimentos , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Soropositividade para HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Perda de Seguimento , Malaui , Avaliação de Processos e Resultados em Cuidados de Saúde , Cooperação do Paciente/psicologia , Gravidez , Cuidado Pré-Natal/psicologia , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Adulto JovemRESUMO
Permanent alopecia after haematopoietic stem cell transplantation (HSCT) is distressing and few studies have investigated this late effect. The aim of the study was to assess the percentage of patients with alopecia and investigate risk factors for alopecia. Patients who underwent allogeneic HSCT before age 19 years, from January 1990 to January 2013, who were at least 2 years after transplant and in follow-up in our clinic were included. Alopecia was defined as clinically apparent decreased hair density. Possible risk factors considered for alopecia after HSCT included: gender, age, diagnosis, donor type, conditioning regimen: cranial irradiation (TBI/cranial radiotherapy) and/or chemotherapy, which chemotherapeutic agents were used and acute/chronic GvHD. The percentage of permanent alopecia in our cohort was 15.6% (41/263 patients). All patients had diffuse alopecia except for one with alopecia totalis. In multivariate analysis, a conditioning regimen with busulphan and busulphan plus fludarabine (odds ratio (OR) 5.7 (confidence interval (CI): 2.5-12.7) and OR 7.4 (CI: 3.3-16.2), respectively, was the main risk factor and associated with alopecia independent of acute/chronic GvHD. Neither TBI nor other alkylating chemotherapy, including treosulfan, was associated with alopecia. In conclusion, permanent alopecia after HSCT is associated with busulphan and GvHD and occurs in 16% of patients.
Assuntos
Alopecia/epidemiologia , Bussulfano/efeitos adversos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/análogos & derivados , Doença Aguda , Adolescente , Adulto , Alopecia/etiologia , Alopecia/patologia , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Humanos , Lactente , Masculino , Fatores de Risco , Condicionamento Pré-Transplante/métodos , Vidarabina/administração & dosagem , Vidarabina/efeitos adversosRESUMO
Every child with a life-limiting or threatening illness, and his or her family, has a right to palliative care. Palliative care is not limited to end-of-life care, but starts from the moment of diagnosis and is independent of whether there are curative options. To optimise quality of life of both the child and the family, the emphasis of care should be on both somatic and psychosocial and spiritual aspects from the very start, and goals should be set together with the child and the family. A multidisciplinary and pro-active approach is essential if this is to be achieved. It is, therefore, strongly recommended that at least every academic hospital should have a multidisciplinary paediatric palliative care team.
Assuntos
Cuidados Paliativos , Equipe de Assistência ao Paciente/organização & administração , Qualidade de Vida , Assistência Terminal/métodos , Criança , Humanos , Lactente , Comunicação Interdisciplinar , MasculinoRESUMO
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 , TranscriptomaRESUMO
INTRODUCTION: Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed with a well-defined methodology and include a systematic search of literature, evidence summaries, and a transparent description of the decision process for the final recommendations. Development of CPGs is time consuming; therefore, it is important to prioritize topics for which there is the greatest clinical demand. OBJECTIVES: This study aims to prioritize childhood cancer supportive care topics for development of CPGs. METHODS: A Delphi survey consisting of two rounds was conducted to prioritize relevant childhood cancer supportive care topics for the development of CPGs. A group of experts comprising 15 pediatric oncologists, 15 pediatric oncology nurses, and 15 general pediatricians involved in care for childhood cancer patients were invited to participate. All relevant supportive care topics in childhood cancer were rated. RESULTS: In both rounds, 36 panellists (82%) responded. Agreement between panellists was very good, with an intraclass correlation coefficient of 0.918 (95% confidence interval (CI) = 0.849-0.966, p < 0.001) in round 2. The ten topics with the highest score in the final round were infection, sepsis, febrile neutropenia, pain, nausea/vomiting, restrictions in daily life and activities, palliative care, procedural sedation, terminal care, and oral mucositis. CONCLUSION: We successfully used a Delphi survey to prioritize childhood cancer supportive care topics for the development of CPGs. This is a first step towards uniform and evidence-based Dutch guidelines in supportive care in childhood cancer. Even though performed nationally, we believe that this study can also be regarded as an example starting point for international development of CPGs in the field of supportive care in cancer or any other field for that matter.
Assuntos
Técnica Delphi , Oncologia/normas , Neoplasias/terapia , Cuidados Paliativos/normas , Pediatria/normas , Guias de Prática Clínica como Assunto , Criança , Necessidades e Demandas de Serviços de Saúde , Humanos , Oncologia/métodos , Países Baixos , Cuidados Paliativos/métodos , Pediatria/métodosRESUMO
BACKGROUND AND AIMS: Varicella zoster virus (VZV) reactivation following hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality. We undertook a retrospective study to determine the frequency and risk factors associated with VZV reactivation, including underlying disease, the use of fludarabine in high-risk leukemia chemotherapy protocols, and immune status before HSCT. PATIENTS AND METHODS: We studied 163 children who underwent a first HSCT between 2002 and 2008, before introduction of routine VZV prophylaxis on our unit. VZV diagnosis was based on clinical features and supported by polymerase chain reaction on plasma and/or vesical fluid. Patient data and possible risk factors pre- and post HSCT were recorded and compared using a multivariate regression analysis. RESULTS: Within this cohort, 41 (25%) patients developed VZV reactivation during the first year after transplantation at a median of 60 days post HSCT. VZV reactivation occurred more often within the subgroup of patients with acute leukemia compared with the remainder of patients (38% vs. 15%, P < 0.01). Multivariate Cox regression analysis revealed that, besides positive VZV serology in patients pre-HSCT (P = 0.03), acute leukemia as the indication for HSCT remained the only independent risk factor for VZV reactivation (P = 0.025, odds ratio 2.5, 95% confidence interval 1.1-5.6). This was associated with low pre-transplant T-cell counts, especially in the CD4(+) subset. No differences were found in relation to donor type, age, or use of serotherapy. CONCLUSION: VZV reactivation after HSCT predominates in acute leukemia patients and is associated with low T CD4(+) lymphocyte counts. This finding demonstrates the impact of pre-HSCT host immune suppression on VZV reactivation patterns after HSCT.
Assuntos
Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 3/fisiologia , Terapia de Imunossupressão/efeitos adversos , Vidarabina/análogos & derivados , Ativação Viral/imunologia , Adolescente , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Humanos , Imunidade Celular/imunologia , Lactente , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Linfócitos T/imunologia , Vidarabina/efeitos adversos , Adulto JovemRESUMO
Since 1968, when Leiden undertook the first successful European pediatric BM transplantation with a 7-year-old sibling donor, more than 300 young children have donated BM in our unit. We first retrospectively studied a cohort of 210 donors, younger than 13 years at donation, to survey procedures of donor eligibility and study immediate effects of BM donation. We then performed a long-term follow-up (FU) and health-related quality of life (HRQoL) study. Despite documentation of previous medical conditions, no child was declared unfit to donate. We found that iron deficiency anemia or low-iron stores in BM did not result in treatment or extended FU. Harvest volumes exceeded 15 mL/kg in 65% of donors, with more than half requiring allogeneic blood transfusions. Donors had no structured FU after their first post-donation control. In this study, 25% of donors reported at least one somatic complaint at long-term FU. Finally long-term HRQoL revealed high scores in most subdomains (representing a higher QoL), compared to norm groups. These results indicate the need for development of (inter)national guidelines for pediatric stem cell donor care management.
Assuntos
Células da Medula Óssea/citologia , Desenvolvimento Infantil , Doação Dirigida de Tecido , Psicologia da Criança , Qualidade de Vida , Doadores de Tecidos/psicologia , Anemia Ferropriva/etiologia , Anemia Ferropriva/prevenção & controle , Anemia Ferropriva/psicologia , Anemia Ferropriva/terapia , Transfusão de Sangue/psicologia , Células da Medula Óssea/patologia , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Seleção do Doador , Seguimentos , Humanos , Lactente , Prontuários Médicos , Países Baixos , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Estudos Retrospectivos , Irmãos , Reação TransfusionalRESUMO
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 HomólogoRESUMO
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 HomólogoRESUMO
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 adversosRESUMO
G-CSF/dexamethasone stimulated donor derived granulocyte transfusion (GTX) has been shown in non-randomized studies to be a useful co-therapy in immune-compromised patients unresponsive to conventional antimicrobial treatments. Reports of GTX are however usually single institution adult experiences. Substantiated pediatric data, other than in neonates, is less common.
Assuntos
Granulócitos/transplante , Adulto , Criança , Humanos , Hospedeiro Imunocomprometido/fisiologia , Recém-Nascido , Consentimento Livre e Esclarecido , Países Baixos , Neutropenia/terapia , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Sistema de RegistrosRESUMO
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 HomólogoRESUMO
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 HomólogoRESUMO
BACKGROUND: Although delayed red cell engraftment and/or hemolysis have been thoroughly documented in association with ABO incompatibility between donor and recipient in patients undergoing hematopoietic stem cell transplantation (HSCT), there are no studies defining the general, long term clinical outcome in a large group of pediatric patients. METHODS: We undertook a retrospective single center analysis of children undergoing pediatric allogeneic stem cell transplantation to determine the influence of ABO donor/recipient incompatibility. Outcome was analyzed according to donor type and included survival, graft versus host disease (GvHD), relapse, days of infection, antibiotic use, transfusion requirement and duration of hospital stay. RESULTS: Two hundred and sixteen children (136 males; 80 females, aged 0-19) transplanted between January 1992 and December 2003 were included in the study. Indications for transplantation were hematological malignancies (n=179) and aplastic conditions (n=37). ABO compatibility was documented in 121 donor/recipient pairs. ABO incompatibility was documented in 95 donor/recipient pairs with 40 major, 40 minor and 15 bi-directional incompatible pairs. ABO incompatibility did not influence survival rate (P=0.3762), the incidence of GvHD (P=0.253) or rate of relapse (P=0.930). Recovery of leucocytes was influenced by ABO incompatibility (P=0.0493), but the rate of infection, transfusion requirements and duration of hospital stay are not. CONCLUSION: In the pediatric setting, ABO major and/or minor mismatch between donor and recipient did not significantly influence the outcome of HSCT. The choice of donor should be determined by the degree of HLA match and CMV status in preference to ABO blood group compatibility.
Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Transplante de Células-Tronco Hematopoéticas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
For many children with life-threatening hematological diseases, hematopoietic stem cell transplantation (HSCT) is the only curative option. In children lacking a matched related or unrelated donor and with the certainty that, left untreated, death will ensue alternative donors must be sought. Haplo-identical peripheral blood stem cell transplantation (PBSCT) from a healthy parent is a feasible alternative. To reduce the risk of fatal graft-versus-host disease (GvHD) as a complication of transplant across major histocompatibility antigens, intense T-cell depletion is required. Large numbers of purified, cytokine mobilized peripheral stem cells (the so-called mega-dose concept) are required to compensate for the significantly increased risk of either graft failure or early rejection. In our unit, despite this approach, graft dysfunction has, in a significant group of children, proved problematic and, despite salvage attempts at re-transplantation, usually fatal. In children with hematological malignant disease, our overall relapse-free survival is 41%. However, successful transplant outcome has been associated with considerable delays in immune reconstitution that can be implicated in subsequent viral reactivation. We are investigating new strategies to improve the outcome of haplo-identical PBSCT, which may allow us to offer this form of treatment to more children requiring urgent HSCT.
Assuntos
Rejeição de Enxerto , Doenças Hematológicas/terapia , Sistema Imunitário , Transplante de Células-Tronco de Sangue Periférico , Recuperação de Função Fisiológica , Adolescente , Antígenos CD34 , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/mortalidade , Humanos , Lactente , Depleção Linfocítica/métodos , Masculino , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Linfócitos T/imunologiaRESUMO
Juvenile myelomonocytic leukemia (JMML) is a childhood leukemia for which allogeneic BMT is the only curative therapy. At our pediatric stem cell transplantation unit, we performed 26 BMTs in 23 children (age 0.5-12.7 years). Conditioning was CY/TBI based (1980-1996, n=14) or BU/CY/melphalan based (1996-2001, n=9). Donors were HLA-identical siblings (n=11), unrelated volunteers (n=9) or mismatched family members (n=3). A total of 10 patients survive in CR (median follow-up 6.8 years, range 3.1-22.2 years). Relapse or persistent disease was observed in eight and two patients, respectively. Nine of these patients died, one achieved a second remission following acute nonlymphatic leukemia chemotherapy (duration to date 5.3 years). Transplant-related mortality occurred in four patients. Overall survival at 5 and 10 years was 43.5%. Using T-cell-depleted, one-antigen mismatched unrelated donors was the only significant adverse factor associated with relapse in multivariate analysis (P=0.039, hazard ratio 4.9). Together with a trend towards less relapse in patients with graft-versus-host-disease and in patients transplanted with matched unrelated donors, this suggests a graft-versus-leukemia effect of allogeneic BMT in JMML.
Assuntos
Transplante de Medula Óssea/métodos , Leucemia Mielomonocítica Crônica/terapia , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro , Efeito Enxerto vs Leucemia , Histocompatibilidade , Humanos , Lactente , Leucemia Mielomonocítica Crônica/mortalidade , Depleção Linfocítica , Masculino , Análise Multivariada , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Resultado do TratamentoRESUMO
We studied the pharmacokinetics of intravenous busulfan (Bu) in children in order to further optimize intravenous Bu dosing in relation to toxicity and survival. A total of 31 children undergoing Bu-based conditioning for allogeneic SCT were enrolled in a study. The starting dose was 1.0 mg/kg (age < 4 years) and 0.8 mg/kg (age > or =4 years), four doses per day during 4 days. Dose adjustment was allowed up to a maximum dose of 1.0 mg/kg per dose if the target area under the serum concentration-time curve (AUC) was not reached. Pharmacokinetic studies were performed after the first dose. Donor engraftment was established in 28 out of 31 patients. The average AUC after the first dose was the same in children < 4 years as in children > or =4 years. Mean clearance was higher in children < 4 years than in children > or =4 years. In 35% of all patients, total AUC was within the target AUC. The other children's AUCs were below the target range. No relationships were found between systemic exposure to Bu and toxicity or clinical outcome. We concluded that, in accordance with previous data, within the observed AUCs no clear relationship was observed between Bu AUC and outcome with respect to toxicity, engraftment and relapse.
Assuntos
Bussulfano/administração & dosagem , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante , Adolescente , Área Sob a Curva , Bussulfano/farmacocinética , Bussulfano/toxicidade , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Hepatopatia Veno-Oclusiva/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Imunossupressores/toxicidade , Lactente , Infusões Intravenosas , Fígado/efeitos dos fármacos , Masculino , Fatores de Tempo , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
Candida albicans and non-C. albicans Candida species are increasingly being isolated from patients in high-risk categories, most notably, those who have undergone stem cell transplantation (SCT). Identification of the presence of non-C. albicans Candida species early in the course of the transplant procedure is important, as these species exhibit different sensitivities to the available antifungal treatments and cause mortality at rates that vary from those for C. albicans. Amplified fragment length polymorphism (AFLP) analysis has been shown to be a reliable method of reproducibly identifying medically important Candida species. We investigated the use of serial AFLP analysis of 54 routine surveillance cultures for the identification and epidemiological examination of Candida sp. colonization in five consecutive children undergoing allogeneic SCT. One child became colonized with a C. albicans strain and remained colonized with this strain during the whole admission period. Another child had persistent colonization with a C. albicans strain with striking variations in its AFLP patterns over time, which was considered indicative of microevolution. Candida dubliniensis, Candida lusitaniae, and Saccharomyces cerevisiae were identified in the three remaining patients, with two children being simultaneously and transiently colonized with different species. These findings show that colonization with yeasts during transplantation is a complex and dynamic interaction between the host and the organism(s). In our study three strains from eight separate time points were incorrectly identified as C. albicans by a rapid enzyme test. AFLP analysis of surveillance cultures allowed more accurate and informative epidemiological evaluations of pathogenic yeasts in children during transplantation.
Assuntos
Candida/classificação , Candidíase/epidemiologia , Técnicas de Tipagem Micológica , Polimorfismo de Fragmento de Restrição , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Candida/genética , Candida/isolamento & purificação , Candida albicans/classificação , Candida albicans/genética , Candida albicans/isolamento & purificação , Candidíase/microbiologia , Criança , Pré-Escolar , Meios de Cultura , HumanosRESUMO
Combinations of symptoms such as general malaise, fever, weight loss and cervical lymphadenopathy have extensive differential diagnoses. In three children, girls aged 11, 13 and 17 years who presented with these symptoms, three different diagnoses were obtained. The first had Hodgkin's disease, the second mixed connective tissue disease (MCTD), and the third Hodgkin's disease in combination with systemic lupus erythematosus (SLE). A systematic approach is necessary for the diagnosis of such conditions. Careful history taking can provide valuable information while a physical examination provides essential clues for the final diagnosis. In particular, nail-fold lesions, tendon nodules and signs of myopathy should be looked for in patients suspected of MCTD and/or SLE. In Hodgkin's disease, generalized or localised lymphadenopathy combined with a short history of extreme fatigue are the most important. Additional investigations should be individualized in order to minimise the diagnostic delay and make possible early treatment.
Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Doença de Hodgkin/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Criança , Doenças do Tecido Conjuntivo/complicações , Diagnóstico Diferencial , Feminino , Febre/etiologia , Doença de Hodgkin/complicações , Humanos , Lúpus Eritematoso Sistêmico/complicações , Doenças Linfáticas/etiologia , Redução de PesoRESUMO
We reviewed the results of the Dutch paediatric bone marrow transplant (BMT) program for children receiving HLA-identical BMT for beta-thalassaemia major over an 18-year period. In all, 19 patients underwent a total of 21 transplants in our treatment centre between July 1984 and February 2002. Eight females (age 0.3-12 years; median 5 years) and 11 males (age 0.8-18 years; median 6 years) were included. Information, prospectively collected, included molecular defects, donor genotype, beta/alpha-globin expression rates, serum ferritin levels, hepato-splenomegaly, chelation history, virology screening, liver pathology together with post-transplant outcome inclusive of leucocyte chimerism. In total, 11 patients received standard busulphan/cyclophosphamide (Bu/Cy) conditioning, with or without ATG. Stable engraftment was seen in 5/11 with late rejection occurring in six patients. Of these, two children underwent a second successful SCT. For this group, overall event-free survival (EFS) and disease-free survival (DFS) were 90 (10/11) and 64% (7/11), respectively. The probability of rejection was 55%. Subsequent addition of melphalan to the conditioning regimen resulted in long-term stable engraftment in all patients with an EFS/DFS for this group of 90% (9/10). Treatment-related mortality, irrespective of conditioning, was low at 5% (1/19 patients). Veno-occlusive disease (VOD) occurred in 19% (4/21 transplants) and acute GvHD in 19% (4/21 transplants). Post-BMT beta/alpha synthetic ratio measurement monitored donor erythroid engraftment and predicted rejection with a return to transfusion dependency. Maintained full donor chimerism is indicative of stable engraftment both for leucocyte and erythroid lineages, whereas mixed donor chimerism is not. Our results emphasise the importance of the conditioning regimen and post-transplant chimerism surveillance predictive of rejection or long-term stable engraftment.