Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Intern Med J ; 53(1): 119-125, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371767

RESUMO

Patients with post-haemopoietic stem cell transplant or chimeric antigen receptor T -cell (CAR-T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high-risk population is needed. Whilst we have learned much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to manage our patients optimally.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Nova Zelândia/epidemiologia , Linfócitos T
2.
BMC Cancer ; 22(1): 985, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109702

RESUMO

BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children's Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children's general and cancer-related health-related quality of life (HRQoL) and parents' emotional well-being. METHODS: Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. RESULTS: Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1-213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children's HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. CONCLUSIONS: It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL.


Assuntos
Pancreatite , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Criança , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários
3.
Pediatr Blood Cancer ; 69(12): e30012, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36129388

RESUMO

We assessed the utility of routine viral surveillance for cytomegalovirus, Epstein-Barr virus and human adenovirus in children <16 years, undergoing autologous stem cell transplantation (ASCT) at a single centre over a 10-year period. A total of 85 ASCT were performed in 65 patients. Routine viral surveillance resulted in a high number of tests performed (median 20 tests per ASCT), without any clinically significant viral detections. These data support the limited clinical utility of routine viral surveillance in children undergoing ASCT. Adopting a clinically driven approach for viral testing is likely to be both cost-effective and safe.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Transplante Autólogo , Herpesvirus Humano 4 , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Estudos Retrospectivos
4.
Am J Dermatopathol ; 44(10): 728-733, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35925552

RESUMO

ABSTRACT: The aim of this study was to review the dermatopathological findings in skin biopsy specimens from pediatric oncology and hematopoietic stem cell transplantation patients over a 20-year period. Three hundred fifty-two skin biopsies from 240 patients were reviewed, and the findings were grouped into 6 categories: index neoplasms, nonindex neoplasms, infections, graft-versus-host disease, other treatment complications, and others. Among the index neoplasms identified on skin biopsy, the most common conditions were Langerhans cell histiocytosis (14 patients) and melanoma (7 patients), with other hematological malignancies and an array of soft-tissue tumors accounting for the bulk of the remainder. Neoplastic conditions common in general dermatopathological practice such as basal cell carcinoma and squamous cell carcinoma were uncommon, each being identified in only 1 patient younger than the age of 18, although basal cell carcinomas developing subsequently in young adult life were identified in 7 patients. Infections were common, with infectious agents or viral cytopathic effects (not including human papillomavirus) identified in 34 biopsies. A significant proportion (74%) represented invasive fungal infections, which are of very significant clinical importance. Biopsies performed for a clinical suspicion of graft-versus-host seldom showed histological features to suggest an alternative diagnosis, with only a single case suggesting a diagnosis of toxic erythema of chemotherapy identified.


Assuntos
Carcinoma Basocelular , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias Cutâneas , Biópsia , Carcinoma Basocelular/complicações , Criança , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Neoplasias Cutâneas/etiologia , Adulto Jovem
5.
Australas J Dermatol ; 62(4): e576-e579, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34398459

RESUMO

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma preferentially involving subcutis. A link between patients with SPTCL and HAVCR2 mutations has recently been discovered. We present a 14-year-old girl of Chinese heritage who was diagnosed with SPTCL in the context of homozygous HAVCR2 status for c.245A>G p. (Tyr82Cys) and achieved complete remission after treatment with cyclosporin and steroids. Dermatologists should be aware of the diagnostic, management and familial genetic counselling utility of HAVCR2 for investigating and managing patients with SPTCL.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A/genética , Linfoma de Células T/genética , Linfoma de Células T/patologia , Mutação/genética , Paniculite/genética , Paniculite/patologia , Adolescente , Feminino , Humanos , Linfoma de Células T/terapia , Paniculite/terapia
6.
Pediatr Transplant ; 24(1): e13602, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31631445

RESUMO

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) using hematopoietic progenitor cells (HPCs) has become an important therapeutic modality for patients with high-risk malignancies. Current literature on standardized method for HPC apheresis in children is sparse and failure rate reported as high as 30%. PATIENTS/METHODS: A retrospective study of 125 pediatric patients with high-risk malignancies undergoing aHSCT in Western Australia between 1997 and 2016 was conducted. RESULTS: Mobilization was achieved by means of chemotherapy and granulocyte colony-stimulating factor (G-CSF). Patients underwent apheresis the day after CD34+ counts reached ≥20/µL and an additional dose of G-CSF. Peripheral arterial and intravenous lines were inserted in pediatric intensive care unit under local anesthetic and/or sedation, omitting the need for general anesthesia as well as facilitating an uninterrupted apheresis flow. Larger apheresis total blood volumes were processed in patients weighing ≤20 kg. The minimal dose of ≥2 × 106 CD34+ cells/kg was successfully collected in 98.4% of all patients. The optimal dose of 3-5 × 106 CD34+ cells/kg was collected in 96% of patients scheduled for a single aHSCT, 87.5% for tandem, and 100% for triple aHSCT. All HPC collections were completed in one apheresis session. Mobilization after ≤3 chemotherapy cycles and cycles including cyclophosphamide resulted in a significantly higher yield of CD34+ cells. CONCLUSION: Our approach to HPC mobilization by means of chemotherapy and single myeloid growth factor combined with optimal collection timing facilitated by continuous apheresis flow resulted in highly effective HPC harvest in children and adolescents with high-risk cancers.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias/terapia , Adolescente , Remoção de Componentes Sanguíneos/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Risco , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
7.
J Paediatr Child Health ; 56(10): 1508-1513, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33099818

RESUMO

This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Imunodeficiência Combinada Severa , Austrália , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Nova Zelândia , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia
9.
J Clin Immunol ; 41(8): 1972-1974, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34478044
11.
Clin Transl Immunology ; 13(9): e70003, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39290230

RESUMO

Objectives: Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications. Methods: Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio. Results: In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non-infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P = 0.02), matched unrelated donor (RR1.34, P = 0.03), peripheral blood (RR 1.36, P = 0.028) or cord blood (RR 1.73, P = 0.012) as the stem cell source and pre-existing lung disease (RR1.72, P < 0.0001). Children with a post-HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P < 0.0001). Conclusion: This study demonstrates pulmonary complications continue to occur frequently in children post-HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre-transplant and enhanced treatments for those who develop lung disease.

12.
Transplant Cell Ther ; 29(6): 383.e1-383.e10, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36934993

RESUMO

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT). Defibrotide is an effective and safe pharmacologic option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centers in Australia and New Zealand, this study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020. Patients who underwent allogeneic hemopoietic stem cell transplantation between 2016 and 2020 were identified from the ABMTRR. Data were extracted for a total of 3346 patients, 2692 from adult centers and 654 from pediatric centers, with a median follow-up of 21.5 months and 33.3 months, respectively. Descriptive statistics were used to describe the patient population, including the incidence of SOS/VOD and defibrotide use. Comparisons were made between patients without SOS/VOD and those with SOS/VOD, divided into defibrotide and no defibrotide cohorts. Associations with overall survival (OS) and day 100 survival with such variables as sex, age, disease at transplantation, stem cell source, conditioning agents, SOS/VOD diagnosis, and use of defibrotide, were determined. The reported incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. Significant variability in the use, dosage, and duration of defibrotide was seen across the adult centers. The day 100 survival rate and median OS for patients managed with defibrotide was 51.8% and 103 days, respectively, for adult patients and 90.4% and not reached, respectively, for pediatric patients. In adults, older age at transplantation, an HLA-matched nonsibling relative donor, and a diagnosis of SOS/VOD treated with defibrotide were associated with reduced OS. In pediatric patients, the patient and transplantation characteristics associated with reduced OS were a diagnosis of SOS/VOD and a ≥2 HLA-mismatched related donor. A collaborative approach across Australasia to diagnosing and managing SOS/VOD, particularly with respect to consistent defibrotide use, is recommended.


Assuntos
Anormalidades Cardiovasculares , Hepatopatia Veno-Oclusiva , Adulto , Criança , Humanos , Anormalidades Cardiovasculares/complicações , Anormalidades Cardiovasculares/tratamento farmacológico , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Incidência , Sistema de Registros , Síndrome , Transplante Homólogo/efeitos adversos , Masculino , Feminino
13.
CPT Pharmacometrics Syst Pharmacol ; 11(8): 1002-1017, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35611997

RESUMO

This study aimed to characterize the population pharmacokinetics (PK) of busulfan focusing on how busulfan clearance (CL) changes over time during once-daily administration and assess different methods for measuring busulfan exposure and the ability to achieve target cumulative exposure under different dosing adjustment scenarios in pediatric stem cell transplantation recipients. Daily serial blood sampling was performed and concentration-time data were analyzed using a nonlinear mixed-effects approach. The developed PK model was used to assess achievement of target exposure under six dose-adjustment scenarios based on simulations performed in RStudio (RxODE package)®. A total of 2491 busulfan plasma concentration-time measurements were collected from 95 patients characterizing 379 dosing days. A two-compartment model with time-associated CL best described the data with a typical CL of 14.5 L/h for an adult male with 62 kg normal fat mass (NFM; equivalent to 70 kg total body weight), typical volume of distribution central compartment (V1) of 40.6 L/59 kg NFM (equivalent to 70 kg total body weight), and typical volume of distribution peripheral compartment of 3.57 L/62 kg NFM. Model interindividual variability in CL and V1 was 14.7% and 34.9%, respectively, and interoccasional variability in CL was 6.6%. Patient size described by NFM, a maturation component, and time since start of treatment significantly influenced CL. Simulations demonstrated that using model-based exposure estimates with each dose, and either a proportional dose-adjustment calculation or model-based calculated individual CL estimates to support dose adjustments, increased proportion of subjects attaining cumulative exposure within 5% of target compared with using noncompartmental analysis (100% vs. 0%). A time-associated reduction in CL during once-daily busulfan treatment was described.


Assuntos
Bussulfano , Administração Intravenosa , Adulto , Peso Corporal , Bussulfano/farmacocinética , Criança , Humanos , Cinética , Masculino
14.
Lancet Child Adolesc Health ; 5(4): 284-294, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33600774

RESUMO

Childhood cancer and its treatment often impact the haematopoietic and lymphatic systems, with immunological consequences. Immunological assessments are not routinely included in surveillance guidelines for most survivors of childhood cancer, although a robust body of literature describes immunological outcomes, testing recommendations, and revaccination guidelines after allogeneic haematopoietic cell transplantation. Survivorship care providers might not fully consider the impaired recovery of a child's immune system after cancer treatment if the child has not undergone haematopoietic cell transplantation. We did a scoping review to collate the existing literature describing immune function after childhood cancer therapy, including both standard-dose chemotherapy and high-dose chemotherapy with haematopoietic cell rescue. This Review aims to summarise: the principles of immunology and testing of immune function; the body of literature describing immunological outcomes after childhood cancer therapy, with an emphasis on the risk of infection, when is testing indicated, and preventive strategies; and knowledge gaps and opportunities for future research.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Reconstituição Imune/imunologia , Síndromes de Imunodeficiência/imunologia , Neoplasias/terapia , Doenças Preveníveis por Vacina/prevenção & controle , Vacinas/uso terapêutico , Imunidade Adaptativa/imunologia , Contagem de Células Sanguíneas , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunidade Inata/imunologia , Síndromes de Imunodeficiência/etiologia , Testes Imunológicos , Baço/imunologia
15.
Bone Marrow Transplant ; 56(12): 2997-3007, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34480120

RESUMO

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/complicações , Recidiva Local de Neoplasia , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos
17.
Pediatr Blood Cancer ; 53(3): 488-90, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19434733

RESUMO

Haemophagocytic lymphohistiocytosis (HLH) is an uncommon disease with a high fatality rate. Etoposide is an important component of current HLH treatment regimes. Two patients with HLH developed etoposide-related secondary acute myeloid leukemia (sAML) following therapy for HLH. Etoposide, an epipodophyllotoxin, is a topoisomerase II inhibitor that interacts with DNA to potentiate leukaemogenesis. The risk of developing sAML is estimated to be between 1% and 5%, 2-20 years after exposure to etoposide but may also be related to cumulative drug doses, treatment schedules, host factors and co-administration of other antineoplastic agents.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Etoposídeo/efeitos adversos , Leucemia Mieloide Aguda/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Segunda Neoplasia Primária/induzido quimicamente , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA