Title: Investigating the long-term outcomes of adult patients who underwent Haematopoietic Stem Cell Transplant for Primary Immunodeficiency during childhood
Funder: Department of Health and Social Care

Abstract: Background: Primary immunodeficiency (PID) describes a number of disorders arising from genetic defects that impair function of the immune system (Fischer et al., 1997). PID presenting in childhood is often severe, resulting in recurrent serious and life threatening infections. Haematopoietic stem cell transplant (HSCT) is the treatment of choice for many paediatric-onset PIDs and is curative in the majority. Despite considerable improvements in survival, HSCT remains a high risk procedure, and is associated with chronic medical complications following treatment. Within the field of HSCT there is consensus that long term follow-up is an important missing data set (Parsons et al., 2012). Data within the field of HSCT for PID is even more limited because most studies have primarily focused on outcomes for HSCT in malignancy, where historically numbers have been greater (Sanders et al., 2010). A few studies have selectively measured psychosocial outcome in children (Cole et al., 2013; Nuss & Wilson, 2007; Skucek et al., 2011, Titman et al., 2008) following HSCT for PID and showed increased rates of cognitive difficulties. However, these studies only addressed outcome for children still in paediatric care and to date no published studies have examined quality of life outcome solely in adult survivors of HSCT for PID in childhood. HSCT techniques have continued to improve and transplants are now more widely performed, so there is an increase in numbers of adult survivors of childhood HSCT, providing power for studies to look at differences in outcome between sub-groups and to identify possible risk factors. As the largest paediatric PID centre within the UK, Great Ormond Street Hospital NHS Foundation Trust now performs approximately 35 HSCT for PID in childhood each year. Long-term follow-up into adulthood is provided through a dedicated clinic at the Royal Free London NHS Foundation trust, providing a unique opportunity to examine adult outcomes for HSCT for PID. Aim: The aim of this project is to evaluate the holistic long-term health outcomes of adult patients who underwent HSCT for PID during childhood, and to identify factors associated with good or poor long-term outcome. Method: All patients aged 16 and over who underwent an HSCT at Great Ormond Street Hospital five years or more previously will be invited to participate in the project. Participants will be contacted by a researcher to arrange an assessment that will gather information on quality of life, psychological functioning and cognitive ability using standardised questionnaires. Medical data will be collated from current and historical medical notes. Information on medical resource usage will also be gathered through a self-designed telephone questionnaire to measure NHS and family costs. A control group will be recruited from siblings of affected patients, or from a nominated friend. Data will also be compared with population norms, where available. Potential Benefit to Patients and the NHS: Identifying health outcomes within this population is critical in providing more information for young people and their families to ensure they are fully informed when making treatment decisions and planning for the future. The information gathered from this study will inform how patients are counselled prior to and following transplant. It will also aid the development of a coherent and targeted package of patient-focused care, engaging appropriate specialities in an efficient and timely manner, and facilitating improvement in the functioning and quality of life of this patient group. Improved service design, for example around transition, will improve patient experience, which is linked to positive patient outcomes, greater adherence to treatment and resource usage (Doyle, Lennox & Bell, 2013) and could provide cost savings for the NHS in the long-term.

Lay abstract: Primary immunodeficiency (PID) represents a group of rare conditions (affecting 1 in 15-20,000 people) that reduce the function of the immune system and result in severe infections. Many PIDs start in childhood and are life-threatening. Treatment includes haematopoietic stem cell transplant (HSCT), which involves replacing the patient s own immune system with donated healthy cells. Due to improved techniques, more transplants are undertaken and patients are living longer. However long-term complications can impact significantly affect future health and quality of life. Previous research has focused on short-term medical outcome. Little is known about health outcomes in adulthood or the social and psychological circumstances of this population. Therefore, this project aims to understand the long-term physical, social and psychological outcomes for a growing population of adults who underwent HSCT for PID during childhood. Patients, aged over 16, who underwent HSCT for PID at Great Ormond Street Hospital, five or more years previously, will be invited to participate. They will be asked to complete questionnaires and practical tasks to assess their current functioning and circumstances. Information will also be gathered from medical notes. Data will be compared with population norms and a control group of siblings or nominated friends. Clinicians, patients, families and patient support groups were involved in the design of the project and will remain involved throughout. Results will be fed back to clinicians, patients and families through conferences and patient meetings, publication in medical journals and patient newsletters. The results will clarify the long-term impact of HSCT for PID and inform improvement of services to address patients needs. For example, earlier psychological input or multi-disciplinary clinics may improve outcomes in adulthood. As HSCT is used for other conditions in childhood, such as leukaemia, these results may provide information to other populations also.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM