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BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC). METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis. RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC. CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.
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Bussulfano , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Humanos , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Bussulfano/farmacocinética , Bussulfano/administração & dosagem , Condicionamento Pré-Transplante/métodos , Masculino , Transplante de Células-Tronco Hematopoéticas/métodos , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Resultado do Tratamento , Estudos Retrospectivos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Tiotepa/uso terapêutico , Tiotepa/administração & dosagem , Tiotepa/farmacocinética , Intervalo Livre de Doença , Seguimentos , Doenças Hematológicas/terapia , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/administração & dosagemRESUMO
Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody-drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice.
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Paediatric chronic pancreatitis (CP) is a relatively rare entity, but it can be accompanied by debilitating complications such as pseudocysts, chronic pain and pancreatic duct obstruction. Surgical drainage procedures, such as pancreaticojejunostomy or cystogastrostomy/jejunostomy to address these complications may be required; however, there is a paucity of evidence as to the efficacy and long-term outcomes of these operations in the paediatric population. A scoping review of contemporary (post-2000) studies detailing surgical pancreatic drainage procedures performed in children (< 18 years) was undertaken. After screening, 24 case series detailing a total of 248 patients met the inclusion criteria. Longitudinal pancreaticojejunostomy and cystogastrostomy were the most common surgical procedures performed in children with CP and pseudocysts, respectively. Overall generally favourable outcomes were reported, but all studies were considered to have a high risk of bias. Operative management for paediatric CP is infrequently required; therefore, large prospective studies or trials focusing on this population are infeasible, limiting the best available evidence on the topic to case series, level IV. Recommendations to improve the quality of surgical care in the paediatric CP population could include centralisation and the formation of registries to allow accurate long-term follow-up.
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Pseudocisto Pancreático , Pancreatite Crônica , Humanos , Criança , Estudos Prospectivos , Drenagem/métodos , Pancreaticojejunostomia/métodos , Pancreatite Crônica/cirurgia , Pâncreas/cirurgia , Pseudocisto Pancreático/etiologiaRESUMO
Thousand and one amino-acid kinase 1 (TAOK1) is a MAP3K protein kinase, regulating different mitogen-activated protein kinase pathways, thereby modulating a multitude of processes in the cell. Given the recent finding of TAOK1 involvement in neurodevelopmental disorders (NDDs), we investigated the role of TAOK1 in neuronal function and collected a cohort of 23 individuals with mostly de novo variants in TAOK1 to further define the associated NDD. Here, we provide evidence for an important role for TAOK1 in neuronal function, showing that altered TAOK1 expression levels in the embryonic mouse brain affect neural migration in vivo, as well as neuronal maturation in vitro. The molecular spectrum of the identified TAOK1 variants comprises largely truncating and nonsense variants, but also missense variants, for which we provide evidence that they can have a loss of function or dominant-negative effect on TAOK1, expanding the potential underlying causative mechanisms resulting in NDD. Taken together, our data indicate that TAOK1 activity needs to be properly controlled for normal neuronal function and that TAOK1 dysregulation leads to a neurodevelopmental disorder mainly comprising similar facial features, developmental delay/intellectual disability and/or variable learning or behavioral problems, muscular hypotonia, infant feeding difficulties, and growth problems.
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Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Aminoácidos , Animais , Humanos , Deficiência Intelectual/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Hipotonia Muscular , Transtornos do Neurodesenvolvimento/genéticaRESUMO
The conserved oligomeric Golgi (COG) complex is involved in intracellular vesicular transport, and is composed of eight subunits distributed in two lobes, lobe A (COG1-4) and lobe B (COG5-8). We describe fourteen individuals with Saul-Wilson syndrome, a rare form of primordial dwarfism with characteristic facial and radiographic features. All affected subjects harbored heterozygous de novo variants in COG4, giving rise to the same recurrent amino acid substitution (p.Gly516Arg). Affected individuals' fibroblasts, whose COG4 mRNA and protein were not decreased, exhibited delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. Despite these abnormalities of the Golgi apparatus, protein glycosylation in sera and fibroblasts from affected subjects was not notably altered, but decorin, a proteoglycan secreted into the extracellular matrix, showed altered Golgi-dependent glycosylation. In summary, we define a specific heterozygous COG4 substitution as the molecular basis of Saul-Wilson syndrome, a rare skeletal dysplasia distinct from biallelic COG4-CDG.
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Síndrome do Cromossomo X Frágil/genética , Transporte Proteico/genética , Proteoglicanas/genética , Proteínas de Transporte Vesicular/genética , Adulto , Substituição de Aminoácidos/genética , Animais , Animais Geneticamente Modificados/genética , Linhagem Celular , Criança , Pré-Escolar , Retículo Endoplasmático/genética , Matriz Extracelular/genética , Feminino , Fibroblastos/patologia , Glicosilação , Complexo de Golgi/genética , Heterozigoto , Humanos , Lactente , Masculino , Peixe-ZebraRESUMO
PURPOSE: Few studies have investigated the health-related quality of life (HRQoL) of young childhood cancer survivors and their parents. This study describes parent and child cancer survivor HRQoL compared to population norms and identifies factors influencing child and parent HRQoL. METHODS: We recruited parents of survivors who were currently <16 years, and >5 years postdiagnosis. Parents reported on their child's HRQoL (Kidscreen-10), and their own HRQoL (EQ-5D-5L). Parents rated their resilience and fear of cancer recurrence and listed their child's cancer-related late effects. RESULTS: One hundred eighty-two parents of survivors (mean age = 12.4 years old and 9.7 years postdiagnosis) participated. Parent-reported child HRQoL was significantly lower than population norms (48.4 vs. 50.7, p < .009). Parents most commonly reported that their child experienced sadness and loneliness (18.1%). Experiencing more late effects and receiving treatments other than surgery were associated with worse child HRQoL. Parents' average HRQoL was high (0.90) and no different to population norms. However 38.5% of parents reported HRQoL that was clinically meaningfully different from perfect health, and parents experienced more problems with anxiety/depression (43.4%) than population norms (24.7%, p < .0001). Worse child HRQoL, lower parent resilience, and higher fear of recurrence was associated with worse parent HRQoL. CONCLUSIONS: Parents report that young survivors experience small but significant ongoing reductions in HRQoL. While overall mean levels of HRQoL were no different to population norms, a subset of parents reported HRQoL that was clinically meaningfully different from perfect health. Managing young survivors' late effects and improving parents' resilience through survivorship may improve HRQoL in long-term survivorship.
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Sobreviventes de Câncer , Neoplasias , Criança , Humanos , Neoplasias/terapia , Pais , Qualidade de Vida , Inquéritos e Questionários , SobreviventesRESUMO
Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.
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Antineoplásicos , Neoplasias , Adolescente , Antineoplásicos/uso terapêutico , Austrália/epidemiologia , Cardiotoxicidade/epidemiologia , Criança , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Nova Zelândia/epidemiologia , Sistema de RegistrosRESUMO
PURPOSE: Four patients with Saul-Wilson syndrome were reported between 1982 and 1994, but no additional individuals were described until 2018, when the molecular etiology of the disease was elucidated. Hence, the clinical phenotype of the disease remains poorly defined. We address this shortcoming by providing a detailed characterization of its phenotype. METHODS: Retrospective chart reviews were performed and primary radiographs assessed for all 14 individuals. Four individuals underwent detailed ophthalmologic examination by the same physician. Two individuals underwent gynecologic evaluation. Z-scores for height, weight, head circumference and body mass index were calculated at different ages. RESULTS: All patients exhibited short stature, with sharp decline from the mean within the first months of life, and a final height Z-score between -4 and -8.5 standard deviations. The facial and radiographic features evolved over time. Intermittent neutropenia was frequently observed. Novel findings included elevation of liver transaminases, skeletal fragility, rod-cone dystrophy, and cystic macular changes. CONCLUSIONS: Saul-Wilson syndrome presents a remarkably uniform phenotype, and the comprehensive description of our cohort allows for improved understanding of the long-term morbidity of the condition, establishment of follow-up recommendations for affected individuals, and documentation of the natural history into adulthood for comparison with treated patients, when therapeutics become available.
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Nanismo , Adulto , Feminino , Humanos , Fenótipo , Estudos RetrospectivosRESUMO
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Neurocognitivos/etiologia , Biomarcadores , Humanos , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/prevenção & controle , Transtornos Neurocognitivos/terapia , Prevalência , Fatores de RiscoRESUMO
Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients of allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research between 1976 and 2008. A case control design was used. There were no CNS tumors in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors (n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic malignancies. In comparison with the general population, pediatric HCT recipients with hematologic malignancies had a 33 times higher than expected rate of CNS tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to 1.87) at 20 years after HCT. Significant risk factors in the entire cohort were having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR, 7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P = .0234) to be significant risk factors. Chronic graft-versus-host disease was associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for nonmalignant diseases did not show an increased incidence of CNS tumors, whereas survivors of hematologic malignancies have a markedly increased incidence of CNS tumors that warrants lifelong surveillance.
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Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Segunda Neoplasia Primária/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doadores não Relacionados , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Lactente , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
BACKGROUND: Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. OBJECTIVE: We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. METHODS: We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). RESULTS: Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). CONCLUSION: Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.
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Linfócitos B/imunologia , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/terapia , Irmãos , Linfócitos T/imunologia , Doadores não Relacionados , Adulto , Austrália , Criança , Quimerismo , Europa (Continente) , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Lactente , Recém-Nascido , Masculino , América do Norte , Estudos Retrospectivos , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/mortalidade , Análise de Sobrevida , Condicionamento Pré-Transplante , Resultado do Tratamento , VoluntáriosRESUMO
INTRODUCTION: Reduced or altered taste and smell function may occur as a side-effect of cancer therapy. This can lead to altered nutrient and energy intake. Some studies have suggested that taste and smell dysfunction can persist many years after treatment completion but this has not been previously assessed in survivors of childhood cancer. The aim of this study is to determine if taste and smell dysfunction is present in childhood cancer survivors (CCS). Food preference and Quality of Life was also assessed. METHODS: Fifty-one child cancer survivors (mean age: 19.69±7.09years), more than five years since treatment completion, (mean: 12.4years) were recruited from the long term follow-up clinics at two Sydney-based children's hospitals. Taste function was assessed using a 25 sample taste identification test comprising five concentrations each of sweet, salty, sour and bitter tastes and water. Smell function was assessed by determining the ability of participants to identify 16 common odorants. The participants' Quality of Life was assessed using the Functional Assessment of Anorexia Cachexia scale and food preferences were assessed using a 94-item food liking tool. RESULTS: Taste dysfunction was found in 27.5% of participants (n=14), and smell dysfunction in 3.9% (n=2) of participants. The prevalence of taste dysfunction was higher than that seen in the non-cancer population. The child cancer survivors' appeared to "like" the less healthy food groups such as flavoured beverages, takeaway and snacks over healthier food groups such as vegetables and salad. No correlation was found between those with a taste dysfunction and their food "likes". CONCLUSION: A high level of taste dysfunction was found in CCS though there did not appear to be an issue with smell dysfunction. Further work is also needed to assess whether a taste dysfunction do play a role in the dietary habits of CCS.
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Neoplasias/fisiopatologia , Transtornos de Sensação/epidemiologia , Olfato/fisiologia , Sobreviventes , Paladar/fisiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Preferências Alimentares , Humanos , Lactente , Masculino , Neoplasias/complicações , Prevalência , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
Sedimentation is a major cause of global near-shore coral reef decline. Although the negative impacts of sedimentation on coral reef community composition have been well-documented, the effects of sedimentation on coral metabolism in situ have received comparatively little attention. Using transcriptomics, we identified gene expression patterns changing across a previously defined sedimentation threshold that was deemed critical due to changes in coral cover and community composition. We identified genes, pathways, and molecular processes associated with this transition that may allow corals, such as Porites lobata, to tolerate chronic, severe sedimentation and persist in turbid environments. Alternative energy generation pathways may help P. lobata maintain a persistent stress response to survive when the availability of light and oxygen is diminished. We found evidence for the expression of genes linked to increased environmental sensing and cellular communication that likely allow P. lobata to efficiently respond to sedimentation stress and associated pathogen challenges. Cell damage increases under stress; consequently, we found apoptosis pathways over-represented under severe sedimentation, a likely consequence of damaged cell removal to maintain colony integrity. The results presented here provide a framework for the response of P. lobata to sedimentation stress under field conditions. Testing this framework and its related hypotheses using multi-omics approaches can deepen our understanding of the metabolic plasticity and acclimation potential of corals to sedimentation and their resilience in turbid reef systems.
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The objective of the study was the analysis of clinical types, outcomes, and risk factors associated with the outcome of adenovirus (ADV) infection, in children and adults after allo-HCT. A total number of 2529 patients (43.9% children; 56.1% adults) transplanted between 2000 and 2022 reported to the EBMT database with diagnosis of ADV infection were analyzed. ADV infection manifested mainly as viremia (62.6%) or gastrointestinal infection (17.9%). The risk of 1-year mortality was higher in adults (p = 0.0001), and in patients with ADV infection developing before day +100 (p < 0.0001). The 100-day overall survival after diagnosis of ADV infections was 79.2% in children and 71.9% in adults (p < 0.0001). Factors contributing to increased risk of death by day +100 in multivariate analysis, in children: CMV seropositivity of donor and/or recipient (p = 0.02), and Lansky/Karnofsky score <90 (p < 0.0001), while in adults: type of ADV infection (viremia or pneumonia vs gastrointestinal infection) (p = 0.0004), second or higher HCT (p = 0.0003), and shorter time from allo-HCT to ADV infection (p = 0.003). In conclusion, we have shown that in patients infected with ADV, short-term survival is better in children than adults. Factors directly related to ADV infection (time, clinical type) contribute to mortality in adults, while pre-transplant factors (CMV serostatus, Lansky/Karnofsky score) contribute to mortality in children.
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Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.
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BACKGROUND: Over the last 25 years, donor source, conditioning, graft-versus-host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high-risk patients in first and subsequent remission. There is a large burden of infectious and pre-HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased. PROCEDURE: A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8-year periods (Period 1: 1/1/1984-31/8/1992, Period 2: 1/9/1992-30/4/2001, Period 3: 1/5/2001-31/12/2009). RESULTS: Despite a significant increase in unrelated donor HSCT, event-free and OS over 25 years improved significantly. (EFS 31.6-64.8%, P = 0.0027; OS 41.8-78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time. CONCLUSION: EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post-HSCT are unchanged, and remain the focus for improvement.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
BACKGROUND: Survival of neuroblastoma patients has improved over recent decades, but chronic health issues and treatment related late effects cause significant morbidity in survivors. AIMS: We aimed to describe late effects and long-term toxicity in neuroblastoma patients treated at a tertiary, paediatric institution in Australia. METHODS & RESULTS: Patients with neuroblastoma treated primarily at The Children's hospital at Westmead were eligible for inclusion. Retrospective analysis of 65 (45 with high-risk and 20 with non-high-risk disease) neuroblastoma patients were performed via medical record review. Approximately 60% of patients were >5 years from diagnosis and termed the "full effects cohort" who had a range of medical and psychosocial late effects analysed through descriptive means. The remaining 26 patients who had not yet reached 5 years post treatment had audiometry analysis only. Of the 65 patients, 72% were alive at last follow-up. The median length of follow-up was 7 years from diagnosis amongst survivors. Therapy was according to contemporary protocols for neuroblastoma and ranged from standard cytotoxic therapies to intensive multimodal regimens and/or experimental therapy depending on risk group/relapse status. Of the 39 full effects cohort, 85% suffered from at least one late effect. Late effects were common in the endocrine, dental and audiometry domains with 38%, 49% and 72% of patients affected in these areas, respectively. Neuro-cognitive domains were also notably affected with 46% of patients suffering a deficit. Two thirds of survivors were disease free at last follow-up. CONCLUSION: Survivors of high-risk neuroblastoma suffer from a range of chronic illnesses, which lead to morbidity and affect quality of life of survivors.
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Neuroblastoma , Qualidade de Vida , Humanos , Criança , Estudos Retrospectivos , Recidiva Local de Neoplasia , Neuroblastoma/epidemiologia , Neuroblastoma/terapia , Morbidade , Progressão da DoençaRESUMO
Introduction: Urosepsis is a significant risk associated with prostate biopsy. Resistance of microorganisms to antibiotics is a challenging issue for clinicians in everyday practice. In the current study, we investigated the rates of sepsis and hospital admissions following transperineal (TP) prostate biopsies using a single dose of gentamicin. Material and methods: Data for consecutive patients who underwent TP prostate biopsies (March 2019-March 2020) were included. Patients received a single-dose of prophylactic gentamicin 120 mg IV and had skin preparation with antiseptic povidone-iodine or chlorhexidine solution prior to the procedure. Patient's electronic records were reviewed for rates of sepsis and readmission to hospital within 7 days following TP prostate biopsy. Results: A total of 365 consecutive patients were included in the study. After exclusion of non-eligible patients, 280 patients were included in final analysis. The median age was 67 years (32-83), the median prostate-specific antigen (PSA) level was 8.5 ng/ml (0.2-58), and the median prostate size was 44 cc (10-188). Approximately 58% of patients had one or more comorbidities in the form of diabetes mellitus (DM), hypertension, asthma, chronic kidney disease, or ischemic heart disease. Adenocarcinoma was found in 71.7% of patients. None of the 280 patients developed sepsis. Urinary tract infection (UTI) occurred in 2.8% of patients with E.coli, none of them required hospital readmission. Conclusions: Our single centre experience showed a 0% sepsis rate after TP prostate biopsy with single prophylactic dose of gentamicin. Future randomized controlled trials (RCTs) should explore the possibility of performing these procedures without antibiotic prophylaxis in order to reduce the unnecessary use of antibiotics.