Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency

Thomas A. Fox, Ronjon Chakraverty, Siobhan Burns, Benjamin Carpenter, Kirsty Thomson, David Lowe, Adele Fielding, Karl Peggs, Panagiotis Kottaridis, Benjamin Uttenthal, Venetia Bigley, Matthew Buckland, Victoria Grandage, Shari Denovan, Sarah Grace, Julia Dahlstrom, Sarita Workman, Andrew Symes, Stephen Mackinnon, Rachael Hough and Emma Morris

Key points

  • Allogeneic HSCT with reduced intensity conditioning is safe and effective in younger adults with severe PID.

  • Referral triggers should include severe infections, autoimmunity, malignancy and disease progression despite conservative management.


Introduction: The primary immunodeficiencies (PID), rare inherited diseases characterised by severe dysfunction of immunity have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. Materials and methods: 29 consecutive adult patients, with a mean age at transplant of 24 years (range 17-50) underwent Allo-HSCT. Reduced intensity conditioning included Flu/Mel/Alemtuzumab (n=20), Flu/Bu/Alemtuzumab (n=8) and Flu/Bu/ATG (n=1). Stem cell donors were matched or mismatched unrelated (MUD/MMUD) (n=18) and matched related donors (MRD) (n=11). Overall survival, event free survival, transplant related mortality, acute and chronic GVHD incidence and severity, time to engraftment, lineage specific chimerism, immune reconstitution and discontinuation of immunoglobulin replacement therapy were recorded. Results: Overall survival (OS) at 3 years for the whole cohort was 85.2%. The rarer, non-CGD PID patients achieved an OS at 3 years of 88.9% (n=18), compared to 81.8% for CGD patients (n=11). Transplant related mortality (TRM) was low with only four deaths observed at a median follow-up of 3.5 years. There were no cases of early or late rejection. In all surviving patients either stable mixed chimerism or full donor chimerism were observed. At last follow-up 87% of the surviving patients had no evidence of persistent or recurrent infections. Conclusion: Allo-HSCT is safe and effective in young adult patients with severe PID and should be considered the treatment of choice where an appropriate donor is available.

  • Submitted September 20, 2017.
  • Accepted December 14, 2017.