Post-Transplant Late Complications Increase Over Time for Patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) Landmark Study.

Overview

abstract

BACKGROUND AND OBJECTIVE: To investigate outcomes of hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID), the Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada in a retrospective, multi-center natural history study. METHODS: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982-2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years post-HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late). RESULTS: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%) and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased height z-score at 2-5 years post-HCT (p<0.001), and endocrine (p<0.001) and dental (p=0.05) CLE. CD4 count ≤500/μl and/or continued need for immunoglobulin replacement >2 years post-transplant were associated with lower height z-scores. Continued survival from 2 to 15 years post-HCT was 90%. The presence of any CLE was associated with increased risk of late death (HR 7.21; 2.71-19.18, p<0.001). CONCLUSION: Late morbidity post-HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposures for patients after HCT for SCID.