Health-related quality of life in survivors of BMT for paediatric malignancy: a systematic review of the literature

Bone Marrow Transplantation (2008) 42, 73–82 & 2008 Macmillan Publishers Limited All rights reserved 0268-3369/08 $30.00 www.nature.com/bmt REVIEW Health-related quality of life in survivors of BMT for paediatric malignancy: a systematic review of the literature S-A Clarke1, C Eiser1 and R Skinner2,3 1 Department of Psychology, University of Sheffield, Sheffield, UK; 2Department of Paediatric and Adolescent Oncology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK and 3Children’s Bone Marrow Transplant Unit, Newcastle General Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK We review evidence concerning health-related quality of life (HRQL) following paediatric haemopoietic stem cell transplant. The aims are to determine (1) HRQL compared with population norms; (2) changes in HRQL over time and (3) relations between pre-transplant variables (disease, individual and family resources) and survivor HRQL. Five databases were searched for articles published between January 1990 and February 2008. A total of 15 studies including 12 separate cohorts were identified. (1) HRQL was comparable with or better than population norms 6 months to 8 years post transplant. (2) HRQL was already compromised pre-transplant, further impaired immediately following conditioning, but improved 4–12 months post transplant. (3) Pre-transplant predictors of HRQL include family functioning and individual resources (for example, social skills). Identification of pre-transplant variables associated with longterm HRQL is invaluable to inform early psychological intervention and facilitate positive adjustment. Bone Marrow Transplantation (2008) 42, 73–82; doi:10.1038/bmt.2008.156; published online 26 May 2008 Keywords: paediatric; leukaemia; health-related quality of life; haemopoietic stem cell transplantation Introduction The number of haemopoietic stem cell transplants (HSCTs) in childhood has increased in recent years, particularly allogeneic transplants for serious haematological disease (malignant and non-malignant). This has been facilitated by developments in use of alternative donors (unrelated or mismatched related) and stem cell sources (PBSCs or umbilical cord blood, UCB). The commonest indication for allogeneic transplantation in children is leukaemia (62%), Correspondence: Dr C Eiser, Department of Psychology, University of Sheffield, Western Bank, Sheffield S10 2TP, UK. E-mail: c.eiser@sheffield.ac.uk Received 22 November 2007; revised 4 March 2008; accepted 23 April 2008; published online 26 May 2008 followed by non-malignant conditions (36%) and other cancers (2%).1 Late adverse consequences of HSCT occur both as a result of original treatment for the disease for which HSCT was performed and secondary to toxicity associated with HSCT-conditioning regimens. Additional damage is sustained through the toxic effects of antibiotics, antifungals or immunosuppressive agents used to prevent or treat infections or GVHD. Chronic GVHD may itself cause late treatment-related toxicity. Cardiac, pulmonary, endocrine, renal, neurological, neuropsychological and other late effects have been recorded. Most children experience at least one late physical effect.2 Published information about late effects typically relates to BMT, but it is anticipated that a similar profile of late effects will be found following PBSC or UCB transplant. Given the toxicity of treatment, questions have been raised about the quality of life of children during and after HSCT. In a medical context, health-related quality of life (HRQL) is generally acknowledged to be a multidimensional concept. Although there are disagreements about definition of HRQL,3 a central assumption is that individuals differ in their perceptions and appraisal of the impact of disease on their daily life.4 Distinctions have been made between generic measures that permit comparisons across conditions regardless of severity or treatment,5 and disease-specific measures, which focus on functional areas of specific concern and are potentially of greater value for clinicians.5 HRQL is potentially compromised at all stages of HSCT. Prolonged hospitalization in a protected environment (for 1–3 months) and social isolation (for at least 3 months) are vital to reduce infection, and can potentially disrupt child and family HRQL.6,7 Typically, children do not attend school for several months,8 and this compromises ageappropriate learning and social relationships.9 Increased dependency on parents, difficulties with resuming age appropriate activities or permanent alterations in developmental trajectory must be anticipated.10 Disruption to family functioning and relationships are especially likely when family donors are used.11 In considering the implications of HSCT for their child, families face an arduous initial period and also an uncertain future. There are questions about survival itself, and also HRQL following paediatric BMT: a systematic review S-A Clarke et al 74 long-term HRQL: will the child experience compromised opportunities and experiences? Furthermore, although adverse HRQL consequences of HSCT must be anticipated in the short term, families are keen to have an indication of the likely time course of recovery; that is can a return to normal life be reasonably anticipated? In coping with chronic illness, there are indications that individual resources (for example, optimism) and family relationships (communication quality) contribute to HRQL over and above characteristics of the disease such as severity.12 Identification of such variables in the context of HSCT would be invaluable for clinic staff, and guide allocation of scarce resources to those most in need. Ultimately, the goal is to identify vulnerable families and provide timely help. Previous reviews have raised questions regarding HRQL and psychosocial adjustment immediately before and shortly after HSCT.13,14 They emphasize the methodological problems inherent in conducting these studies, the range of outcome measures used, and apparent discrepancies between severity of physical problems and survivor or parent ratings of HRQL. Our goal was to contribute further to the literature by focusing specifically on studies using validated measures of HRQL. In addition, we focus on longer-term survivors. We conducted a systematic literature search of the empirical evidence to determine (1) HRQL compared with population norms; (2) changes in HRQL over time and (3) relations between pre-transplant variables (disease, individual and family resources) and HRQL. Method Recommended review methods were employed15 to ensure a systematic literature search. Five databases (OVID Medline (1966–January week 5, 2008), CINAHL, Psychinfo (1990–February week 1, 2008, British Nursing Index (1994–2008) and Journals@OvidFulltext (7 February 2008)) were searched using Boolean logic with the following terms: stem cell transplant, BM (...truncated)