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ObjectivePatients with congenital heart disease (CHD) have an increased cancer risk. The aim of this study was to determine cancer-related mortality in CHD patients compared with non-CHD controls, compare ages at cancer diagnosis and death, and explore the most fatal cancer diagnoses.DesignRegistry-based cohort study.Setting and participantsCHD patients born between 1970 and 2017 were identified using Swedish Health Registers. Each was matched by birth year and sex with 10 non-CHD controls. Included were those born in Sweden with a cancer diagnosis.ResultsCancer developed in 758 out of 67814 CHD patients (1.1%), with 139 deaths (18.3%)—of which 41 deaths occurred in patients with genetic syndromes. Cancer was the cause of death in 71.9% of cases. Across all CHD patients, cancer accounted for 1.8% of deaths. Excluding patients with genetic syndromes and transplant recipients, mortality risk between CHD patients with cancer and controls showed no significant difference (adjusted HR 1.17; 95% CI 0.93 to 1.49). CHD patients had a lower median age at cancer diagnosis—13.0 years (IQR 2.9–30.0) in CHD versus 24.6 years (IQR 8.6–35.1) in controls. Median age at death was 15.1 years (IQR 3.6–30.7) in CHD patients versus 18.5 years (IQR 6.1–32.7) in controls. The top three fatal cancer diagnoses were ill-defined, secondary and unspecified, eye and central nervous system tumours and haematological malignancies.ConclusionsCancer-related deaths constituted 1.8% of all mortalities across all CHD patients. Among CHD patients with cancer, 18.3% died, with cancer being the cause in 71.9% of cases. Although CHD patients have an increased cancer risk, their mortality risk post-diagnosis does not significantly differ from non-CHD patients after adjustements and exclusion of patients with genetic syndromes and transplant recipients. However, CHD patients with genetic syndromes and concurrent cancer appear to be a vulnerable group.

Aims Individuals with congenital heart disease (CHD) are at an increased risk for cancer. As cancer survival rates improve, the prevalence of late side effects, such as heart failure (HF), is becoming more evident. This study aims to evaluate the risk of developing HF following a cancer diagnosis in patients with CHD, compared with those without CHD and with CHD patients who do not have cancer. Methods CHD patients (n = 69 799) and randomly selected non‐CHD controls (n = 650 406), born in Sweden between 1952 and 2017, were identified from the Swedish National Health Registers and Total Population Register (excluding those with syndromes and transplant recipients). CHD patients who developed cancer (n = 1309) were propensity score‐matched with non‐CHD patients who developed cancer (n = 9425), resulting in a cohort of 1232 CHD patients with cancer and 2602 non‐CHD controls with cancer (after exclusion of individuals with HF prior to cancer diagnosis). In a separate analysis, CHD patients with cancer were propensity score‐matched with CHD patients without cancer (n = 68 490). A total of 1233 CHD patients with cancer and 2257 CHD patients without cancer were included in the study. Results Among CHD patients with cancer, 73 (5.9%) developed HF during a mean follow‐up time of 8.5 ± 8.7. Comparatively, in the propensity‐matched control population, 29 (1.1%) non‐CHD cancer patients (mean follow‐up time of 7.3 ± 7.5) and 101 (4.5%) CHD patients without cancer (mean follow‐up time of 9.9 ± 9.2) developed HF. CHD patients exhibited a significantly higher risk of HF post‐cancer diagnosis compared with the non‐CHD control group [hazard ratio (HR) 4.39, 95% confidence interval (CI) 2.83–6.81], after adjusting for age at cancer diagnosis and comorbidities. In the analysis between CHD patients with cancer and those without cancer, the results indicated a significantly higher risk of developing HF in CHD patients with cancer (HR 1.53, 95% CI 1.13–2.07). Conclusions CHD patients face a more than four‐fold increased risk of developing HF after a cancer diagnosis compared with cancer patients without CHD. Among CHD patients, the risk of HF is only modestly higher for those with cancer than for those without cancer. This suggests that the increased HF risk in CHD patients with cancer, relative to non‐CHD cancer patients, may be more attributable to CHD itself than to cancer treatment‐related side effects.

Purpose: Adolescents with cerebral palsy may need a feeding tube due to feeding challenges, since nutritional intake and mealtimes may be negatively affected. The purpose of the study was to describe and better understand how one adolescent with cerebral palsy and her parents experienced mealtimes before and after a nasogastric and gastrostomy tube insertion and how the use of these feeding tubes was experienced in daily life. Methods: Individual interviews were performed with one adolescent and each of her parents. In total, six interviews were conducted on two separate occasions. The qualitative approach known as Interpretive Description was used during the analysis. Results: Four thematic patterns were identified within the data: (i) struggling with nutritional intake, (ii) the paradox of using an aid, (iii) being different, and (iv) challenges of public mealtimes. Conclusions: The results showed that four themes influenced daily mealtimes in adolescents with cerebral palsy and a gastrostomy tube. Nutritional intake and mealtimes may be difficult, which is why using a gastrostomy tube can be a relief. However, the gastrostomy tube can also pose a challenge and a paradox. Time of change and acceptance seems necessary in order to meet these challenges.

Background Children with cancer often suffer side effects from their treatment, for example nausea and vomiting, which can lead to malnutrition. If a child cannot eat orally, a percutaneous endoscopic gastrostomy (PEG) can improve his or her well-being, psychosocial development and growth by enabling the supply of nourishment and facilitating the administration of necessary medicines. Few data exist on children’s comfort when using a PEG. The aim of this study was firstly to develop three versions of a web-based assessment tool in which children, families, and healthcare professionals would be able to register their observations and assessments for evaluating the meal situation when a child has a PEG and secondly to validate the content of the tool. Methods A qualitative design was chosen with purposive sampling of participants. Five children with cancer, five parents, five registered nurses and five paediatricians participated first in an interview and then in a member check of the web-based tool. The data were analysed with manifest qualitative content analysis. Results The results highlighted four categories of issues which needed to be revised in the web-based tool: words which were difficult for the participants to understand, items which contained several questions, items which needed to be split into more items to be answerable and the layout of the questionnaire. The web-based tool was revised according to the categories, and then a member check evaluated and finally confirmed the revisions. Conclusions A web-based tool may be able to evaluate the meal situation when a child with cancer has a PEG. The tool may be able to detect early failures of the PEG, facilitating early action from the healthcare professionals in supporting the child and his or her parents in their care of the PEG. In the long run, this web-based tool may also be able to increase the quality of care of children living with a PEG.

Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells. analyses of patient samples, combined with experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway. Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes. The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

There is a well-known knowledge gap regarding the efficacy and safety of medicines in children of all ages, and clinical trials and the need for new treatments were recently listed among the most important factors for child health. Pediatric clinical trials are faced with several challenges compared with trials in adults. These challenges include the fact that pediatric populations are small and heterogenous, and that there is generally less experience with pediatric clinical trials,, compared to trials in adults both on the sponsor side and at the hospitals. One specific challenge that has received little attention is the importance of adequate representation of costs in pediatric trial budgets. The aim with the present study was to describe some important aspects to consider when a pediatric clinical trial budget is reviewed and identify budget items that often need adjustments in pediatric clinical trials. We went through the budgets negotiations of the last ten trials sponsored by the pharmaceutical industry where agreements between our site, the Pediatric Clinical Research Center, and the sponsor, had been finalized. The therapy areas represented among these trials were pediatric oncology (2), neurology (4), gastroenterology, neuropsychiatry, cardiology, and nephrology. We reviewed the trial budgets and identified areas where discrepancies between the sponsor´s initial budget, and the final budget, negotiated and agreed between sponsor and site, may arise. The difference in total budget amount between the initial budget and the final budget was +60% (mean 59%, range 31 to 139%). The costs for preparation of the clinical trial, time spent for study activities, and costs for examinations were identified as key budget items for these differences. Our findings indicate that a substantial part of the trial-related costs would not be covered by the sponsor had the initial budget been accepted. A thorough review at the site and budget negotiation with the sponsor, and to have within the site team a person with specific competence for the budget review and negotiation, are therefore essential to ensure equitable responsibility for the study-related costs and avoid discontinuation of the trials. High-quality pediatric trials are essential to ensure that children have the benefit of treatments based on the same quality of evidence that guides treatment in adults.

Purpose To evaluate the feasibility of oral cryotherapy (OC) in children and to investigate if OC reduces the incidence of severe oral mucositis (OM), oral pain, and opioid use in children undergoing hematopoietic stem cell transplantation (HSCT) . Methods Fifty-three children, 4–17 years old, scheduled for HSCT in Sweden were included and randomized to OC or control using a computer-generated list. OC instructions were to cool the mouth with ice for as long as possible during chemotherapy infusions with an intended time of ≥ 30 min. Feasibility criteria in the OC group were as follows: (1) compliance ≥ 70%; (2) considerable discomfort during OC < 20%; (3) no serious adverse events; and (4) ice administered to all children. Grade of OM and oral pain was recorded daily using the WHO-Oral Toxicity Scale (WHO-OTS), Children’s International Oral Mucositis Evaluation Scale, and Numerical Rating Scale. Use of opioids was collected from the medical records. Results Forty-nine children (mean age 10.5 years) were included in analysis (OC = 26, control = 23). The feasibility criteria were not met. Compliance was poor, especially for the younger children, and only 15 children (58%) used OC as instructed. Severe OM (WHO-OTS ≥ 3) was recorded in 26 children (OC = 15, control = 11). OC did not reduce the incidence of severe OM, oral pain, or opioid use. Conclusion The feasibility criteria were not met, and the RCT could not show that OC reduces the incidence of severe OM, oral pain, or opioid use in pediatric patients treated with a variety of conditioning regimens for HSCT. Trial registration ClinicalTrials.gov id: NCT01789658

The impact of conditioning regimen prior to hematopoietic cell transplant (HCT) in pediatric AML-patients is not well studied. We retrospectively analyzed the impact of Busulfan–Cyclophosphamide (BuCy), Busulfan–Cyclophosphamide–Melphalan (BuCyMel) and Clofarabine–Fludarabine–Busulfan (CloFluBu) in pediatric AML-patients, with similar upfront leukemia treatment (NOPHO-DBHconsortium), receiving an HCT between 2010 and 2015. Outcomes of interest were LFS, relapse, TRM and GvHD. 103 patients were included; 30 received BuCy, 37 BuCyMel, and 36 CloFluBu. The 5-years LFS was 43.3% (SE ± 9.0) in the BuCy group, 59.2 % (SE ± 8.1) after BuCyMel, and 66.7 % (SE ± 7.9) after CloFluBu. Multivariable Cox regression analysis showed a trend to lower LFS after BuCy compared to CloFluBu (p = 0.07). BuCy was associated with a higher relapse incidence compared to the other regimens (p = 0.06). Younger age was a predictor for relapse (p = 0.02). A strong correlation between Busulfan Therapeutic Drug Monitoring (TDM) and lower incidence of aGvHD (p < 0.001) was found. In conclusion, LFS after BuCyMel and CloFluBu was comparable, lower LFS was found after BuCy, due to higher relapse incidence. CloFluBu was associated with lower incidence of aGvHD, suggesting lower toxicity with this type of conditioning. This finding is also explained by the impact of Busulfan monitoring.

Hemorrhagic cystitis (HC) is a debilitating complication following allogenic hematopoietic cell transplantation (HCT). HLA disparity and T-cell depletion have been implicated as risk factors for HC. However, reports on the incidence and risk factors for HC in ex vivo T-cell depleted haploidentical HCT (haploHCT) in children are lacking. We studied 96 haploHCT procedures performed in 83 children between 2002 and 2017. Sixty-three patients were diagnosed with a malignant disease and 20 with nonmalignant disease. All but three patients with SCID underwent myelotoxic and/or lymphotoxic conditioning therapy. Grafts were CD3+ (36.5%) or TcRαβ+ (63.5%) depleted to prevent graft versus host disease (GvHD). Fourteen patients (14.6%) were diagnosed with HC; 12 (12.5%) had clinically significant stage II–IV HC. All patients with HC had BK viruria and/or viremia. Increasing age and chemotherapeutic treatment prior to conditioning were identified as risk factors for HC. Immune recovery did not significantly differ between patients with and without HC. Thus, we report a low incidence of HC in pediatric haploHCT using ex vivo T-cell depletion. The combination of a reduced toxicity conditioning regimen, and typically absent pharmaceutical post-HCT GvHD prophylaxis in our patients might have contributed to the decreased the risk of HC, despite HLA disparity.