Assessing We-Disease Appraisals of Health Problems: Development and Validation of the We-Disease Questionnaire.

In couples dealing with health problems, we-disease appraisals can influence dyadic coping strategies to alleviate distress. This study describes the development and validation of a self-report scale to assess we-disease appraisals of health problems. The newly developed We-Disease Questionnaire (WDQ) was administered in three samples: parents of children with type 1 diabetes (n = 240) or cancer (n = 125) and individuals with visual impairment and their partners (n = 216). Reliability was measured by coefficient omega. To assess construct validity, correlations with other measures of individual and dyadic adjustment were examined. Descriptive statistics across all samples were compared. A 4-item version of the WDQ demonstrated good reliability and validity and showed meaningful associations with established scales. We-disease appraisals were highest among parents of children with cancer and lowest among couples with visual impairment. The WDQ is a reliable and valid measure that can be used across different health problems.

Cognition, psychosocial functioning, and health-related quality of life among childhood cancer survivors.

Long-term sequelae of cancer and its treatment render childhood cancer (CC) survivors vulnerable to cognitive and behavioural difficulties and likely affect their quality of life (QoL). Our aim was to compare levels of cognition, psychosocial functioning, and health-related QoL of CC survivors to healthy controls and examine the associations between these three domains. Seventy-eight CC survivors (age range = 7-16 years, ≥ one year since cancer treatment) and 56 healthy controls were included. Cognition (i.e., fluid intelligence, executive functions, memory, processing speed, and selective attention), psychosocial functioning, and health-related QoL were assessed using standardized tests and questionnaires. The cognitive performance, parent-reported psychosocial behaviour, and health-related QoL of the CC survivors were within the normative range. However, working memory was significantly poorer in survivors than controls, and visuospatial working memory below the normative range was more commonly observed among survivors than among controls. Processing speed significantly predicted survivors' performance in executive functions. Among survivors, greater peer problems were significantly associated with poorer cognitive functions and health-related QoL. Despite the evidence for good intellectual functioning, which might point towards adequate reserves, in some survivors, domain-specific difficulties may emerge years after cancer relating to psychosocial development and QoL.

The Working Memory Network and Its Association with Working Memory Performance in Survivors of non-CNS Childhood Cancer.

Childhood cancer and its treatment puts survivors at risk of low working memory capacity. Working memory represents a core cognitive function, which is crucial in daily life and academic tasks. The aim of this functional MRI (fMRI) study was to examine the working memory network of survivors of childhood cancer without central nervous system (CNS) involvement and its relation to cognitive performance. Thirty survivors (aged 7-16 years, ≥ 1 year after cancer treatment) and 30 healthy controls performed a visuospatial working memory task during MRI, including a low- and a high-demand condition. Working memory performance was assessed using standardized tests outside the scanner. When cognitive demands increased, survivors performed worse than controls and showed evidence for slightly atypical working memory-related activation. The survivor group exhibited hyperactivation in the right-hemispheric superior parietal lobe (SPL) in the high- compared to the low-demand working memory condition, while maintaining their performance levels. Hyperactivation in the right SPL coincided with poorer working memory performance outside the scanner in survivors. Even in survivors of childhood cancer without CNS involvement, we find neural markers pointing toward late effects in the cerebral working memory network.AbbreviationsfMRI: Functional magnetic resonance imaging; CNS: Central nervous system; MNI: Montreal Neurological Institute; SES: Socioeconomic status; SPL: Superior parietal lobe.

Cortical Morphometry and Its Relationship with Cognitive Functions in Children after non-CNS Cancer.

Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7-16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, ŋ2 = .117) and the striatum (p = .03, ŋ2 = .102) was reduced in Ccs. No significant structure-function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.

Motor ability, physical self-concept and health-related quality of life in pediatric cancer survivors.

BACKGROUND: Cancer survivorship is frequently associated with severe late effects. However, research into pediatric cancer survivors on late effects in motor ability, physical self-concept and their relationship to quality of life is limited. METHODS: Using multiple regression analyses, 78 pediatric cancer survivors and 56 typically developing children were compared in motor ability, physical self-concept and health-related quality of life. In addition, mediational multi-group analyses between motor ability (independent variable), physical self-concept (mediator) and quality of life (dependent variable) were calculated. RESULTS: Pediatric cancer survivors had a lower motor ability (gHedges  = 0.863), a lower physical self-concept with regard to several scales of the PSDQ-S (gHedges  = 0.318-0.764) and a higher relative risk for a below average quality of life than controls (RR = 1.44). Children with a history of cancer involving the central nervous system showed poorer motor ability compared to those without central nervous system involvement (gHedges  = 0.591). Furthermore, the physical self-concept significantly mediated the relationship between motor ability and quality of life in pediatric cancer survivors but not in typically developing children. CONCLUSIONS: Results show the importance of monitoring and supporting the development of motor ability in the aftercare of pediatric cancer survivors. Physical activity interventions may be advisable to prevent physical activity-related late effects and potentially improve related psychosocial variables such as quality of life.

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition.

INTRODUCTION: Non-central nervous system cancer in childhood (non-CNS CC) and its treatments pose a major threat to brain development, with implications for functional networks. Structural and functional alterations might underlie the cognitive late-effects identified in survivors of non-CNS CC. The present study evaluated resting-state functional networks and their associations with cognition in a mixed sample of non-CNS CC survivors (i.e., leukemia, lymphoma, and other non-CNS solid tumors). METHODS: Forty-three patients (off-therapy for at least 1 year and aged 7-16 years) were compared with 43 healthy controls matched for age and sex. High-resolution T1-weighted structural magnetic resonance and resting-state functional magnetic resonance imaging were acquired. Executive functions, attention, processing speed, and memory were assessed outside the scanner. RESULTS: Cognitive performance was within the normal range for both groups; however, patients after CNS-directed therapy showed lower executive functions than controls. Seed-based connectivity analyses revealed that patients exhibited stronger functional connectivity between fronto- and temporo-parietal pathways and weaker connectivity between parietal-cerebellar and temporal-occipital pathways in the right hemisphere than controls. Functional hyperconnectivity was related to weaker memory performance in the patients' group. CONCLUSION: These data suggest that even in the absence of brain tumors, non-CNS CC and its treatment can lead to persistent cerebral alterations in resting-state network connectivity.

Effects of Cognitive Training and Exergaming in Pediatric Cancer Survivors-A Randomized Clinical Trial.

PURPOSE: Although most pediatric cancer patients survive, those who undergo anticancer treatments like chemotherapy and/or radiotherapy are at a high risk for late effects, such as cognitive deficits. To counteract these deficits, feasible and effective interventions are needed. The aim of this study was to compare the effects of working memory training, exergaming, and a wait-list control condition on cognitive functions in pediatric cancer survivors. METHODS: In a parallel-group randomized trial, 69 pediatric cancer survivors aged 7-16 yr (mean = 11.35, SD = 3.53) were randomly assigned to 8-wk working memory training, exergaming, or a wait-list control group. Each training course consisted of three 45-min training sessions per week. The primary outcome comprised the core executive functions (visual working memory, inhibition, switching), and the secondary outcomes included other cognitive domains (intelligence, planning, memory, attention, processing speed), motor abilities, and parent rating on their children's executive functions. Assessments were conducted both before and immediately after the interventions, and at 3-month follow-up. RESULTS: Linear mixed models revealed that participants in the working memory training group showed a linear improvement in visual working memory after training and at follow-up compared with the control group. No other intervention effects of either type of training could be detected. CONCLUSION: This study presents evidence that working memory training improves visual working memory in pediatric cancer survivors. Results show that near-transfer, but no far-transfer effects can be expected from working memory training. Multiple-component interventions tailored to fit the individual's cognitive profile are needed to best support cognitive development after cancer and its treatment.

39·0°C versus 38·5°C ear temperature as fever limit in children with neutropenia undergoing chemotherapy for cancer: a multicentre, cluster-randomised, multiple-crossover, non-inferiority trial.

BACKGROUND: Fever in neutropenia is the most frequent complication of chemotherapy for cancer. The temperature limit defining fever used clinically varies. A higher limit can avoid unnecessary diagnoses in patients spontaneously recovering from fever. This trial primarily aimed to determine if a limit of 39·0°C ear temperature is non-inferior to 38·5°C regarding safety. METHODS: This cluster-randomised, multiple crossover, non-blinded, non-inferiority trial was done in six Swiss Paediatric Oncology Group centres (clusters) in Switzerland. Patients (aged 1 to <18 years) with any malignancy and treated with myelosuppressive chemotherapy expected to last 2 months or more were repeatedly randomly assigned (1:1), at the cluster level, to either monthly 39·0°C or 38·5°C ear temperature limits for diagnosis of fever in neutropenia. Diagnosis below the randomised limit was allowed for clinical reasons. Such a diagnosis implied emergency hospitalisation, examinations (including blood culture), as-needed antipyretics, and empirical intravenous broad-spectrum antibiotics. The primary outcome was the rate of fever in neutropenia with safety relevant events (SRE) per chemotherapy year; we also assessed efficacy in terms of rate of fever in neutropenia. The non-inferiority margin was 1·33 for safety, and for effiacy, the superiority margin was 1·00. This trial is registered at ClinicalTrials.gov, number NCT02324231. FINDINGS: 269 patients were recruited between April 28, 2016, to Aug 27, 2018, until the trial was stopped for success after the second interim analysis. Patients were repeatedly randomly assigned, with 1210 (48%) of 2547 randomisation periods and 92 (47%) of 195 chemotherapy years randomised to 39·0°C. SREs were diagnosed in 72 (20%) of 360 fever in neutropenia episodes (zero deaths, 16 intensive care unit admissions, 22 cases of severe sepsis, and 56 cases of bacteraemia). In 92 chemotherapy years randomised to the 39·0°C fever limit, 151 episodes of fever with neutropenia were diagnosed (1·64 per year), including 22 (15%) with SRE (0·24 per year). In 103 chemotherapy years randomised to 38·5°C, 209 episodes were diagnosed (2·03 per year), including 50 (24%) with SRE (0·49 per year). The mixed Poisson regression rate ratio (RR) of fever in neutropenia with SRE in 39·0°C versus 38·5°C was 0·56 (95% upper confidence bound 0·72). The corresponding RR of fever in neutropenia was 0·83 (95% upper confidence bound 0·98). INTERPRETATION: In children with neutropenia and chemotherapy for cancer, 39·0°C ear temperature was safe and seemed efficacious. For Switzerland and comparable settings, 39·0°C can be recommended as new evidence-based standard fever limit except for patients with acute myeloid leukaemia or haematopoietic stem cell transplantation. FUNDING: Swiss Cancer League (KLS-3645-02-2015).

Peripheral blood progenitor cell collection in pediatric patients optimized by high pre-apheresis count of circulating CD34+ cells and high blood flow.

Collection of peripheral blood progenitor cells by leukapheresis is the preferred method to obtain grafts for autologous transplantation. Optimizing this procedure is important to warrant sufficient cell yield and reduce associated risks. To obtain sufficient to optimal yields of ≥ 2 to ≥ 5 × 106 CD34+ cells/kg body weight with a single leukapheresis procedure, success rates between 83 and 92% have been reported in children. In this retrospective study, we describe an improved protocol for autologous stem cell collection with an extraordinarily high success rate applied in 122 consecutive pediatric patients treated at the University Hospital Bern between 2004 and 2017. By comparing our data with previous studies, we identify two main optimizing factors: higher pre-apheresis CD34+ cell counts with a median of 130/µl and higher blood flow rates of 42-100 ml/min. Consequently, blood volumes processed were increased, duration of leukapheresis was shorter and CD34+ cell yields with a median of 19.0 × 106/kg body weight were higher than previously described. Safety in our study was comparable to previous studies. Based on our data, we present an innovative algorithm for determination of the necessary blood volume and time of pediatric leukapheresis procedure.

Nonalimental Scurvy With Relapse Symptoms After Stopping Oral Vitamin C Supplementation.

Historically linked to sea voyagers in the 18th century, scurvy has become extremely rare during the last century in developed countries. However, it is still present in some at-risk populations and often overlooked in pediatric patients with restricted diets due to behavioral, neurodevelopmental, or psychiatric problems. So far, the only known etiology of developing scurvy is nutritional deficiency of vitamin C. In this report, we describe the case of a 3-year-old previously healthy Swiss girl without any history of previous poor dietary intake, who presented a picture of systemic inflammation including persisting fever, palpable purpura located on the extensor sides of the extremities, refusal to bear weight, and gingival bleeding. Blood tests revealed a significant increase of inflammatory markers and hypoalbuminemia. Full-body MRI revealed symmetrical bone marrow edema consistent with findings in previously reported cases of children with scurvy. After starting a high-dose oral vitamin C supplementation, the patient showed rapid clinical, laboratory, and radiologic improvement, but after stopping the treatment 4 months later, the patient developed relapse symptoms with pronounced fatigue, refusing to walk, and hair loss. These symptoms led us to restart the oral supplementation, which resulted in secondary normalization of her condition. The cause of her symptoms still remains unclear and presents the first case to our knowledge describing scurvy symptoms that are not directly linked to deficient dietary intake.

Haematopoietic cell transplantation in Switzerland, changes and results over 20 years: a report from the Swiss Blood Stem Cell Transplantation Working Group for Blood and Marrow Transplantation registry 1997-2016.

In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997-2006) and second decade (2007-2016) of the registry. There were numerous changes over time. For allogeneic HCT, transplant rates, and therefore use of HCT technology, increased from 14 to 21.8 HCTs per 1 million inhabitants per year from the first to the second decade. Likewise autologous HCTs increased from 24.8 to 37.2 annually corrected for population growth. Allogeneic transplant recipients were older (38.4 vs 48.3 years) and more frequently had unrelated donors in the second decade. Similarly, age increased for recipients of autologous HCT (50.8 vs 56.4 years). Analysis of outcome showed that the probabilities of overall and progression-free survival were stable over time, in spite of the treatment of older and higher risk patients. In multivariate analysis, nonrelapse mortality decreased in recipients of allogeneic HCT (relative risk 0.68, 95% confidence interval 0.52-0.87) over the two decades. Improvement in adjusted nonrelapse mortality compensated for the fact that higher risk patients were treated in more recent years, resulting in similar overall survival. Five-year survival probabilities were 56% (53-59%) in the first and 54% (51-57%) in the second decade for allogeneic HCT, and 59% (57-61%) in the first and 61% (59-63%) in the second decade for autologous HCT. Detailed analyses of changes over time are presented. This study included all HCTs performed in Switzerland during the period of observation and the data are useful for quality assurance programmes, healthcare cost estimation and healthcare planning. Between 50 and 60% of patients were long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care and observation.

Pediatric patients at risk for fever in chemotherapy-induced neutropenia in Bern, Switzerland, 1993-2012.

Fever in neutropenia (FN) is the most frequent potentially life threatening complication of chemotherapy for cancer. Prediction of the risk to develop FN during chemotherapy would allow for targeted prophylaxis. This retrospective, single centre cohort study in pediatric patients diagnosed with cancer before 17 years covered two decades, 1993 to 2012. The 583 (73%) of 800 patients diagnosed with cancer who had received chemotherapy were studied here. Data on 2113 observation periods was collected, defined by stable combinations of 11 predefined characteristics potentially associated with FN. They covered 692 years of cumulative chemotherapy exposure time, during which 712 FN episodes were diagnosed, 154 (22%) of them with bacteremia. The risk to develop FN and FN with bacteremia remained stable over time. These data can mainly be used to study FN risks over time and between centers, and to derive or externally validate FN risk prediction rules.

The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer.

BACKGROUND: There is no evidence-based definition of the temperature limit defining fever (TLDF) in children with neutropenia. Lowering the TLDF is known to increase the number of episodes of fever in neutropenia (FN). This study aimed to investigate the influence of a lower versus standard TLDF on diagnostics and therapy. METHODS: In a single pediatric cancer center using a high standard TLDF (39°C tympanic-temperature) patients were observed prospectively (NCT01683370). The effect of applying lower TLDFs (range 37.5°C to 38.9°C) versus 39.0°C on these measures was simulated in silicon. RESULTS: In reality, 45 FN episodes were diagnosed. Of 3391 temperatures measured, 193 were ≥39.0°C, and 937 ≥38.0°C. For persisting fever ≥24 hours, additional blood cultures were taken in 31 (69%) episodes in reality. This number decreased to 22 (49%) when applying 39.0°C, and increased to 33 for 38.0°C (73%; plus 11 episodes; plus 24%). For persisting fever ≥48 hours, i.v.-antibiotics were escalated in 25 (56%) episodes. This number decreased to 15 (33%) when applying 39.0°C, and increased to 26 for 38.0°C (58%; plus 11 episodes; plus 24%). For persisting fever ≥120 hours, i.v.-antifungals were added in 4 (9%) episodes. This number increased to 6 (13%) by virtually applying 39.0°C, and to 11 for 38.0°C (24%; plus 5 episodes; plus 11%). The median length of stay was 5.7 days (range, 0.8 to 43.4). In 43 episodes with hospital discharge beyond 24 hours, applying 38.0°C led to discharge delay by ≥12 hours in 24 episodes (56%; 95% CI, 40 to 71), with a median delay of 13 hours, and a cumulative delay of 68 days. CONCLUSION: Applying a low versus standard TLDF led to relevant increases of diagnostics, antimicrobial therapy, and length of stay. The differences between management in reality versus simply applying 39.0° as TLDF reflect the important impact of clinical assessment.

Patterns of paediatric end-of-life care: a chart review across different care settings in Switzerland.

BACKGROUND: Paediatric end-of-life care is challenging and requires a high level of professional expertise. It is important that healthcare teams have a thorough understanding of paediatric subspecialties and related knowledge of disease-specific aspects of paediatric end-of-life care. The aim of this study was to comprehensively describe, explore and compare current practices in paediatric end-of-life care in four distinct diagnostic groups across healthcare settings including all relevant levels of healthcare providers in Switzerland. METHODS: In this nationwide retrospective chart review study, data from paediatric patients who died in the years 2011 or 2012 due to a cardiac, neurological or oncological condition, or during the neonatal period were collected in 13 hospitals, two long-term institutions and 10 community-based healthcare service providers throughout Switzerland. RESULTS: Ninety-three (62%) of the 149 reviewed patients died in intensive care units, 78 (84%) of them following withdrawal of life-sustaining treatment. Reliance on invasive medical interventions was prevalent, and the use of medication was high, with a median count of 12 different drugs during the last week of life. Patients experienced an average number of 6.42 symptoms. The prevalence of various types of symptoms differed significantly among the four diagnostic groups. Overall, our study patients stayed in the hospital for a median of six days during their last four weeks of life. Seventy-two patients (48%) stayed at home for at least one day and only half of those received community-based healthcare. CONCLUSIONS: The study provides a wide-ranging overview of current end-of-life care practices in a real-life setting of different healthcare providers. The inclusion of patients with all major diagnoses leading to disease- and prematurity-related childhood deaths, as well as comparisons across the diagnostic groups, provides additional insight and understanding for healthcare professionals. The provision of specialised palliative and end-of-life care services in Switzerland, including the capacity of community healthcare services, need to be expanded to meet the specific needs of seriously ill children and their families.

The Brainfit study: efficacy of cognitive training and exergaming in pediatric cancer survivors - a randomized controlled trial.

BACKGROUND: Cancer survival comes at a price: pediatric cancer survivors bear a high risk for a wide range of cognitive difficulties. Therefore, interventions targeting these difficulties are required. The aim of the present clinical trial is to extend empirical evidence about efficacy of cognitive and physical training in pediatric cancer survivors. It is hypothesized that early cognitive and physical interventions affect the remediation of pediatric cancer survivors in terms of improved executive functions (primary outcome). Additional positive effects of cognitive and physical intervention to other areas such as memory and attention are expected (secondary outcome). Changes in cognitive performance are expected to be associated with structural and functional changes in the brain. METHODS: Overall, 150 pediatric cancer survivors and 50 matched controls will be included in this trial. The cancer survivors will be randomly assigned to either a computerized cognitive training, a physical training (exergaming) or a waiting control group. They will be assessed with neuropsychological tests, tests of sport motor performance and physical fitness before and after 8 weeks of training and again at a 3-months follow-up. Moreover, neuroimaging will be performed at each of the three time points to investigate the training impact on brain structure and function. DISCUSSION: With increasing cancer survival rates, evidence-based interventions are of particular importance. New insights into training-related plasticity in the developing brain will further help to develop tailored rehabilitation programs for pediatric cancer survivors. TRIAL REGISTRATION: KEK BE 196/15; KEK ZH 2015-0397; ICTRP NCT02749877 ; date of registration: 30.11.2016; date of first participant enrolment: .18.01.2017.

2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner.

In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response.

Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years.

The outcome of AML patients ≥65 years remains disappointing. Current post-induction strategies for elderly AML patients fit for intensive treatment involve additional cycles of chemotherapy or allogeneic transplantation. Consolidation with autologous transplantation (ASCT) is poorly studied in these patients. In this single-center retrospective analysis, we determined survival rates of AML patients ≥65 years undergoing busulfan/cyclophosphamide conditioning before ASCT in first remission between 2007 and 2015. We found elderly AML patients with ASCT to have longer progression-free survival (PFS; 16.3 vs. 5.1 months, P=0.0166) and overall survival (OS; n.r. vs. 8.2 months; P=0.0255) than elderly AML patients without ASCT consolidation. In addition, elderly AML patients undergoing ASCT had comparable PFS (P=0.9462) and OS (P=0.7867) as AML patients below 65 years receiving ASCT consolidation in CR1. Our data suggest that ASCT is an option in elderly fit AML patients who appear to benefit from autologous consolidation similarly to younger AML patients.

BeEAM conditioning with bendamustine-replacing BCNU before autologous transplantation is safe and effective in lymphoma patients.

BEAM with BCNU is commonly used for conditioning treatment followed by autologous stem cell transplantation (ASCT). However, pulmonary toxicity and availability issues associated with BCNU prompted us to evaluate bendamustine-replacing BCNU (BeEAM). We analyzed 39 lymphoma patients receiving BeEAM conditioning with 200 mg/m2 bendamustine at days -7 and -6. The median duration until neutrophil recovery was 11 days, and 15 days for platelet recovery (>20 g/L). The most common grade 3/4 non-hematologic toxicities comprised mucosal side effects (27 pts.). Pulmonary toxicity was observed in one patient (2.5%), and one patient died of septic complications. The CR rate increased from 33% to 74% 100 days after ASCT. After a median follow-up of 18.5 months, progression and death each occurred in 11 patients (28%). Median progression-free and overall survival at 2 years were 69% and 72%. Our data suggest that BeEAM conditioning using bendamustine is safe and results in promising survival rates.

Cognitive dysfunction in children with brain tumors at diagnosis.

BACKGROUND: Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo- and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS). METHODS: Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1-16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and his/her parent(s) completed self-report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy, or irradiation. Groups were comparable with regard to age, gender, and socioeconomic status. RESULTS: Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory, and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed, and verbal comprehension were preserved at the time of measurement. CONCLUSION: Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school.