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.