Post HSCT Follow-up - Version 1
Research type
Research Study
Full title
Investigating the long-term outcomes of patients who underwent Haematopoietic Stem Cell Transplant for Primary Immunodeficiency during childhood
IRAS ID
197235
Contact name
Mari Campbell
Contact email
Sponsor organisation
Royal Free London NHS Foundation Trust
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Summary of Research
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.Summary of Results
Allogeneic Haematopoietic 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 long-term health or psychosocial outcomes in adulthood.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. Participants also undertook questionnaires and practical tasks assessed their current functioning and circumstances and information was also gathered from medical notes. Data was compared with population norms and a control group of participant-nominated siblings or friends (N = 46).
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. 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 was 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.
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. 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 maximise holistic outcomes. 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.
REC name
Wales REC 6
REC reference
16/WA/0147
Date of REC Opinion
2 Jun 2016
REC opinion
Further Information Favourable Opinion