Raphaële R. L. van Litsenburg

Impaired sleep affects quality of life in children during maintenance treatment for acute lymphoblastic leukemia: an exploratory study

BackgroundWith the increase of pediatric cancer survival rates, late effects and quality of life (QoL) have received more attention. Disturbed sleep in pediatric cancer is a common clinical observation, but research on this subject is sparse. In general, sleep problems can lead to significant morbidity and are associated with impaired QoL. Information on sleep is essential to develop interventions to improve QoL.MethodsChildren (2-18 years) with acute lymphoblastic leukemia (ALL) were eligible for this multi-center study. The Childrens Sleep Habits Questionnaire (CSHQ), Child Health Questionnaire (CHQ) and Pediatric Quality of Life Inventory 3.0™ Acute Cancer Version (PedsQL) were used to assess sleep and QoL halfway through maintenance therapy. Sleep and QoL were measured during and after dexamethasone treatment (on-dex and off-dex).ResultsSeventeen children participated (age 6.7 ± 3.3 years, 44% boys). Children with ALL had more sleep problems and a lower QoL compared to the norm. There were no differences on-dex and off-dex. Pain (r = -0.6; p = 0.029) and worry (r = -0.5; p = 0.034) showed a moderate negative association with sleep. Reduced overall QoL was moderately associated with impaired overall sleep (r = -0.6; p = 0.014) and more problems with sleep anxiety (r = -0.8; p = 0.003), sleep onset delay (r = -0.5; p = 0.037), daytime sleepiness (r = -0.5; p = 0.044) and night wakenings (r = -0.6; p = 0.017).ConclusionQoL is impaired in children during cancer treatment. The results of this study suggest that impaired sleep may be a contributing determinant. Consequently, enhanced counseling and treatment of sleep problems might improve QoL. It is important to conduct more extensive studies to confirm these findings and provide more detailed information on the relationship between sleep and QoL, and on factors affecting sleep in pediatric ALL and in children with cancer in general.

Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well‐being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. This cross‐sectional study examined sleep and fatigue in relation to depression and quality of life (QoL) after treatment for childhood ALL.

Cost‐effectiveness of treatment of childhood acute lymphoblastic leukemia with chemotherapy only: The influence of new medication and diagnostic technology

Survival for childhood acute lymphoblastic leukemia (ALL) has reached 80–90%. Future improvement in treatment success will involve new technologies and medication, adding to the pressure on limited financial resources. Therefore a retrospective cost‐effectiveness analysis of ALL treatment with chemotherapy only according to the two most recent Dutch Childhood Oncology Group treatment protocols was performed. The most recent protocol ALL10 included more expensive medication (pegasparaginase) and implemented a new diagnostic technique (minimal residual disease levels) compared to the previous ALL9 protocol.

Cost-analysis of treatment of childhood acute lymphoblastic leukemia with asparaginase preparations: the impact of expensive chemotherapy

Asparaginase is an expensive drug, but important in childhood acute lymphoblastic leukemia. In order to compare costs of PEGasparaginase, Erwinia asparaginase and native E. coli asparaginase, we performed a cost-analysis in the Dutch Childhood Oncology Group ALL-10 medium-risk group intensification protocol. Treatment costs were calculated based on patient level data of 84 subjects, and were related to the occurrence of allergy to PEGasparaginase. Simultaneously, decision tree and sensitivity analyses were conducted. The total costs of the intensification course of 30 weeks were

Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

57,893 in patients without PEGasparaginase allergy (n=64). The costs were significantly higher (

Health Status Utilities in Pediatrics A Systematic Review of Acute Lymphoblastic Leukemia

113,558) in case of allergy (n=20) necessitating a switch to Erwinia asparaginase. Simulated scenarios (decision tree analysis) using native E. coli asparaginase in intensification showed that the costs of PEGasparaginase were equal to those of native E. coli asparaginase. Also after sensitivity analyses, the costs for PEGasparaginase were equal to those of native E. coli asparaginase. Intensification treatment with native E. coli asparaginase, followed by a switch to PEGasparaginase, and subsequently to Erwinia asparaginase in case of allergy had similar overall costs compared to the treatment with PEGasparaginase as the first-line drug (followed by Erwinia asparaginase in the case of allergy). PEGasparaginase is preferred over native E. coli asparaginase, because it is administered less frequently, with less day care visits. PEGasparaginase is less immunogenic than native E. coli asparaginase and is not more expensive. Asparaginase costs are mainly determined by the percentage of patients who are allergic and require a switch to Erwinia asparaginase.

The prevalence and risk factors of sleep problems in pediatric oncology: its effect on quality of life during and after cancer treatment

Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypothalamic-pituitary-adrenal (HPA) axis. The duration of HPA axis suppression is not yet well defined. The present study aimed at assessing the function of the HPA axis by determining the cortisol awakening response (CAR) and the dexamethasone (DEX) suppression test in children that were treated for childhood ALL, compared to a healthy age and sex matched reference group. In addition, questionnaires regarding sleep, fatigue, depression and quality of life were completed by the children and their parents. Fourty-three survivors who finished their treatment for childhood ALL 37 (interquartile range 22-75) months before and 57 healthy controls were included. No differences in CAR were observed between ALL survivors and the reference group, but survivors of ALL had higher morning cortisol levels and an increased cortisol suppression in response to oral dexamethasone. Higher cortisol levels in childhood ALL survivors were associated with more fatigue and poorer quality of life. We conclude that the experience of a stressful life event in the past may have caused a long-term dysregulation of the HPA axis in childhood ALL survivors, as reflected in an increased cortisol production and an enhanced negative feedback mechanism.

A cost analysis of individualized asparaginase treatment in pediatric acute lymphoblastic leukemia

Background. Measuring utilities and health-related quality of life (HRQL) in children is challenging due to their cognitive abilities and changing developmental stages. Purpose. To identify methodological issues on utility measurements in children, we performed a systematic review on utilities measured with a single instrument, the Health Utilities Index (HUI), in pediatric acute lymphoblastic leukemia (ALL). The secondary goal was to facilitate future cost-utility analyses without the need for time-consuming assessments. Data Sources. PubMed, Embase, Cochrane Library, CINAHL, and PsycINFO were searched from inception to June 2012. Studies had to report on utility scores in pediatric ALL, either on or after treatment, to be included. Results. Fifteen studies were included. Most studies had methodological shortcomings, which mainly concerned study design and definition and representativeness of the study group. Utility scores were dependent on treatment variables, and there generally was an improvement in HRQL as treatment or survivorship advanced. In general, proxy-respondents were less reliable for subjective phenomena than for observable conditions. HUI2 and HUI3 scores were not interchangeable. Limitations. Studies may have been missed because no validated search method for utility studies exists, due to language bias or the exclusion of non–peer-reviewed papers. Conclusions. Most studies in this review were methodologically suboptimal. Future developments should focus on including developmentally appropriate items for the whole pediatric age group. Adding disease-specific domains may enhance the sensitivity and responsiveness of instruments. Efforts should be undertaken to elicit valuation of health states from older children and teenagers as much as possible. For now, it remains difficult to make valid and informed decisions on the financing of interventions until health state valuation in children has become more methodologically robust.

A cost-effectiveness analysis of Erwinia asparaginase therapy in children with acute lymphoblastic leukemia

ABSTRACT This review aims to describe the prevalence, types and risk factors of sleep problems in children undergoing cancer treatment and in childhood cancer survivors. Furthermore, the relation between sleep and quality of life (QoL) was described. In children undergoing treatment sleep problems were more common compared to norms and controls. In survivors results were more inconsistent and in some studies even less sleep problems were reported. In both populations various sleep problems were reported (such as night awakenings, bedtime resistance, and daytime sleepiness). Several demographic, disease and treatment related factors were associated with sleep outcomes. Impaired sleep was associated with poorer physical, psychosocial, and cancer-related QoL. Sleep was assessed with a variety of measurements, all measuring different sleep constructs, limiting the formulation of generalizable conclusions. Therefore, a standardized way to assess sleep in different age categories in pediatric oncology is mandatory.

Sleep habits and sleep disturbances in Dutch children: a population-based study

Therapeutic drug monitoring (TDM) of asparaginase is necessary to respond to variability in asparaginase activity levels, detect silent inactivation, and distinguish between real allergies and allergic‐like reactions with and without asparaginase neutralization, respectively. In this study, the costs of an individualized and fixed asparaginase dosing schedule were compared.