Quality of Life and Social and Psychological Outcomes in Adulthood Following Allogeneic HSCT in Childhood for Inborn Errors of Immunity.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) is well established as a corrective treatment for many inborn errors of immunity (IEIs) presenting in childhood. Due to improved techniques, more transplants are undertaken and patients are living longer. However, long-term complications can significantly affect future health and quality of life. Previous research has focused on short-term medical outcomes and little is known about health or psychosocial outcomes in adulthood. OBJECTIVE: This project aimed to ascertain the long-term social and psychological outcomes for adults who underwent HSCT for IEI during childhood. METHODS: Adult patients, who had all undergone HSCT for IEI during childhood at two specialist immunology services at least 5 years previously, were invited to participate in the study. Questionnaires and practical tasks assessed their current functioning and circumstances. Information was also gathered from medical notes. Data was compared with population norms and a control group of participant-nominated siblings or friends. RESULTS: Eighty-three patients and 46 matched controls participated in the study. Patients reported significantly better physical health-related quality of life than the general population norm, but significantly worse than matched controls. Patient's self-reported physical health status and the perceived impact of their physical health on everyday life were worse than matched controls and patients reported higher levels of anxiety and lower mood than the general population. For those where their IEI diagnosis was not associated with a learning disability, cognitive function was generally within the normal range. CONCLUSIONS: Patients who have had a HSCT in childhood report mixed psychosocial outcomes in adulthood. More research is needed to establish screening protocols and targeted interventions to maximize holistic outcomes. CLINICAL IMPLICATIONS: Screening for holistic needs and common mental health difficulties should be part of routine follow-up. Information should be provided to patients and families in order to support decision-making regarding progression to transplant and the early identification of any difficulties.

Retrospective, Landmark Analysis of Long-term Adult Morbidity Following Allogeneic HSCT for Inborn Errors of Immunity in Infancy and Childhood.

PURPOSE: Allogeneic hematopoietic stem cell transplant (HSCT) remains the treatment of choice for patients with inborn errors of immunity (IEI). There is little published medical outcome data assessing late medical complications following transition to adult care. We sought to document event-free survival (EFS) in transplanted IEI patients reaching adulthood and describe common late-onset medical complications and factors influencing EFS. METHODS: In this landmark analysis, 83 adults surviving 5 years or more following prior HSCT in childhood for IEI were recruited. The primary endpoint was event-free survival, defined as time post-first HSCT to graft failure, graft rejection, chronic infection, life-threatening or recurrent infections, malignancy, significant autoimmune disease, moderate to severe GVHD or major organ dysfunction. All events occurring less than 5 years post-HSCT were excluded. RESULTS: EFS was 51% for the whole cohort at a median of 20 years post HSCT. Multivariable analysis identified age at transplant and whole blood chimerism as independent predictors of long-term EFS. Year of HSCT, donor, conditioning intensity and underlying diagnosis had no significant impact on EFS. 59 events occurring beyond 5 years post-HSCT were documented in 37 patients (45% cohort). A total of 25 patients (30% cohort) experienced ongoing significant complications requiring active medical intervention at last follow-up. CONCLUSION: Although most patients achieved excellent, durable immune reconstitution with infrequent transplant-related complications, very late complications are common and associated with mixed chimerism post-HSCT. Early intervention to correct mixed chimerism may improve long-term outcomes and adult health following HSCT for IEI in childhood.

Fatigue, executive function and psychological effects in children with immune thrombocytopenia: a cross-sectional study.

Childhood ITP is often considered to be a relatively mild haematological disorder, with only a minority of patients requiring treatment for troublesome bleeding. Over recent years, wider effects of the condition have been identified in some adults, particularly relating to fatigue and cognitive impairment. In this study, we sought to investigate such effects in a group of children with ITP and further our understanding of their psychological profile. Children attending routine haematology outpatient clinics and their parents were asked to complete standardised questionnaires designed to assess a range of psychological and cognitive factors. Although the majority of children had some scores within the normal range, a significantly high proportion had difficulties with fatigue (70·6%), emotional and behavioural symptoms (25·7%) or executive functioning (19·4%). Quality of life and subjective evaluation of the illness (appraisal) correlated significantly with each of these domains, but bleeding severity and platelet count did not. Our findings provide valuable insight into the broader impact of childhood ITP, which could aid in providing holistic care, potentially contribute to decisions regarding medical treatment, and guide future research.

Interventions to improve the mental health of children and young people with long-term physical conditions: linked evidence syntheses.

BACKGROUND: Although mental health difficulties can severely complicate the lives of children and young people (CYP) with long-term physical conditions (LTCs), there is a lack of evidence about the effectiveness of interventions to treat them. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of interventions aiming to improve the mental health of CYP with LTCs (review 1) and explore the factors that may enhance or limit their delivery (review 2). DATA SOURCES: For review 1, 13 electronic databases were searched, including MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Science Citation Index. For review 2, MEDLINE, PsycINFO and CINAHL were searched. Supplementary searches, author contact and grey literature searches were also conducted. REVIEW METHODS: The first systematic review sought randomised controlled trials (RCTs) and economic evaluations of interventions to improve elevated symptoms of mental ill health in CYP with LTCs. Effect sizes for each outcome were calculated post intervention (Cohen's d). When appropriate, random-effects meta-analyses produced pooled effect sizes (d). Review 2 located primary qualitative studies exploring experiences of CYP with LTCs, their families and/or practitioners, regarding interventions aiming to improve the mental health and well-being of CYP with LTCs. Synthesis followed the principles of metaethnography. An overarching synthesis integrated the findings from review 1 and review 2 using a deductive approach. End-user involvement, including topic experts and CYP with LTCs and their parents, was a feature throughout the project. RESULTS: Review 1 synthesised 25 RCTs evaluating 11 types of intervention, sampling 12 different LTCs. Tentative evidence from seven studies suggests that cognitive-behavioural therapy interventions could improve the mental health of CYP with certain LTCs. Intervention-LTC dyads were diverse, with few opportunities to meta-analyse. No economic evaluations were located. Review 2 synthesised 57 studies evaluating 21 types of intervention. Most studies were of individuals with cancer, a human immunodeficiency virus (HIV) infection or mixed LTCs. Interventions often aimed to improve broader mental health and well-being, rather than symptoms of mental health disorder. The metaethnography identified five main constructs, described in an explanatory line of argument model of the experience of interventions. Nine overarching synthesis categories emerged from the integrated evidence, raising implications for future research. LIMITATIONS: Review 1 conclusions were limited by the lack of evidence about intervention effectiveness. No relevant economic evaluations were located. There were no UK studies included in review 1, limiting the applicability of findings. The mental health status of participants in review 2 was usually unknown, limiting comparability with review 1. The different evidence identified by the two systematic reviews challenged the overarching synthesis. CONCLUSIONS: There is a relatively small amount of comparable evidence for the effectiveness of interventions for the mental health of CYP with LTCs. Qualitative evidence provided insight into the experiences that intervention deliverers and recipients valued. Future research should evaluate potentially effective intervention components in high-quality RCTs integrating process evaluations. End-user involvement enriched the project. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001716. FUNDING: The National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

Many children and young people with a long-term physical health condition also experience feelings of depression, anxiety and other mental health issues that affect their day-to-day life, their family and others around them. This review investigates whether or not interventions (treatments, strategies and resources) can help children and young people with their mental health. The study also reviewed studies that explored the attitudes and experiences of those involved in receiving or delivering similar interventions. The study found 25 publications that evaluated 11 different types of interventions, including cognitive­behavioural therapy (seven studies) and music therapy (one study). There were some positive effects for the strategies tested on both mental health and other outcomes, but, because the studies were often small, exact effects were uncertain. Many of the studies were not very well designed or carried out and differences between research designs meant that it was hard to compare different studies. The study found 57 publications that explored experiences of interventions. Analysis suggested that it is important that strategies involve building good relationships and are delivered in what feels like a safe space. Participants in studies tended to like interventions that provided social support and helped them feel better about living with a long-term physical condition. Successful interventions were viewed as accessible and engaging. These studies were often conducted well, but they focused on the range of interventions rather than the review evaluating how well interventions work. There are many gaps in the research carried out so far. Some long-term conditions affecting children and young people have not been the subject of studies of mental health interventions, and some important outcomes, such as school attendance and self-care, have not been assessed. More carefully designed UK research consulting children and young people, parents and practitioners is needed before it can be clear what works for children with particular physical conditions to help their mental health, and why.

Cognitive and psychosocial function post hematopoietic stem cell transplantation in children with hemophagocytic lymphohistiocytosis.

OBJECTIVES: This study investigated the cognitive and psychosocial outcomes in childhood survivors of hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation. METHODS: Twenty-one children were assessed on standardized measures of cognitive and psychosocial functioning and compared with an unaffected sibling control group (n = 14). Parent and teacher reports were obtained to provide additional information. RESULTS: The average full-scale intelligence quotient for the patient cohort was 81 (95% CI, 72-90), which was significantly lower than both the population average of 100 (P = .001) and the average for the unaffected sibling control group (99.2, P = .002). Fifty-six percent of school-aged children were receiving additional support at school, with the majority needing high levels of support. These children also experienced significant psychosocial difficulties. Lower socioeconomic status was associated with poorer cognitive outcomes, but age at transplantation, time to transplantation, type of conditioning, and presence of mixed chimerism were not. Ten (48%) of 21 children had evidence of neurologic involvement at diagnosis, but surprisingly, this was not significantly associated with adverse neurologic outcomes, and some children who did not have any apparent neurologic involvement at diagnosis had severe learning difficulties at follow-up. CONCLUSIONS: In summary, childhood survivors of hemophagocytic lymphohistiocytosis are at risk of long-term cognitive and psychosocial difficulties. Prospective and systematic long-term follow-up of these patients is essential for early identification and effective management of these problems.

Cognitive ability in children with chronic granulomatous disease: a comparison of those managed conservatively with those who have undergone hematopoietic stem cell transplant.

Chronic granulomatous disease (CGD) is a primary immunodeficiency managed conservatively or with hematopoietic stem cell transplant. Studies have shown people with CGD and those transplanted for primary immunodeficiencies have lower than average cognitive ability. In this study, IQ in children with CGD and those transplanted for it was within the normal range.

Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant.

PURPOSE: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency that predisposes to life-threatening infections and inflammation. Haematopoietic stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of life. Children with haematological malignancies report improved quality of life post-HSCT. There are no data for children with CGD. This study evaluated quality of life and emotional well-being in CGD children treated conventionally or transplanted. METHODS: Parents and children completed the Pediatric Quality of Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ). Mean scores were compared with published UK norms. Comparisons were made for those that had or had not undergone HSCT. RESULTS: Forty-seven parents completed PedsQL (children aged 3-15). Twenty-one were post-HSCT. Forty-two completed SDQ (children aged 3-15). Nineteen post-HSCT. Median age for non-HSCT group 9 years. Median age for post-HSCT group 10 years. The HSCT group were median 3 years post-HSCT (range 1-9 years). HSCT survival was 90 %-two died without completing questionnaires Parent and self-reported quality of life for non-transplanted children was significantly lower than healthy children. Parents reported increased emotional difficulties compared to published norms. PedsQL and SDQ scores for transplanted children were not significantly different from healthy norms. CONCLUSIONS: This study demonstrates the quality of life is reduced in CGD. Transplanted patients have quality of life comparable to levels reported in healthy children. This data will help inform families and clinicians when deciding about treatment and may have relevance for other immunodeficiencies treated with transplant.

Parents' experiences one year on from their child's hematopoietic stem cell transplant for primary immunodeficiency.

This study explored parental experience one year after hematopoietic stem cell transplant for primary immunodeficiency. Eight parents whose child had undergone transplant were interviewed one year after their child's transplant. Transcripts were analysed using interpretative phenomenological analysis. Four themes emerged: parents' paradoxical existence within an 'abnormal normality'; isolation felt by parents; gender differences between mothers and fathers; and the 'positive growth' parents attribute to their experience. As well as describing stressful or traumatic experiences they identified aspects of post-traumatic growth. The methodology used allowed contrasting experiences to emerge and highlights the importance of follow-up for parents as well as children.

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies.

Hematopoietic stem cell transplantation (HSCT) is a highly successful treatment for severe congenital immunodeficiencies. However, some studies have suggested that children may experience cognitive difficulties after HSCT. This large-scale study assessed cognitive and behavioral function for the cohort of children treated by HSCT at one center between 1979 and 2003 to determine the frequency and severity of problems and to identify risk factors. A total of 105 patients were assessed on standardized measures of cognitive and emotional and behavioral function together with a control group of unaffected siblings. The average IQ for the cohort was 85 (95% confidence interval, 81-90), significantly lower than both the population average of 100 (P < .001) and unaffected siblings. Multivariate analysis indicated that the underlying genetic defect, diagnosis of adenosine deaminase-deficient severe combined immunodeficiency, and consanguinity were associated with worse outcome but that age at transplantation and chemotherapy conditioning were not. Children treated by HSCT for severe immunodeficiency have an increased risk of long-term cognitive difficulties and associated emotional and behavioral difficulties. The specific genetic diagnosis, consanguinity, and severe clinical course are associated with poor outcome. Long-term follow-up of these patients should include screening to identify and manage these problems more effectively.