International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome

Dimitrova D., Nademi Z., Maccari M. E., Ehl S., Uzel G., Tomoda T., ...More

Journal of Allergy and Clinical Immunology, vol.149, no.1, pp.410, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 149 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1016/j.jaci.2021.04.036
  • Journal Name: Journal of Allergy and Clinical Immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.410
  • Keywords: Primary immunodeficiency, activated phosphoinositide 3-kinase delta syndrome, lymphoproliferation, allogeneic hemato-poietic cell transplantation, graft failure, mTOR inhibitor, serotherapy, 3-KINASE DELTA SYNDROME, HUMAN IMMUNODEFICIENCY, MUTATIONS, DISEASE, PIK3CD
  • Kayseri University Affiliated: No


© 2021Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT). Objectives: This study sought to characterize HCT outcomes in APDS. Methods: Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT. Results: Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure–free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT. Conclusions: Graft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time.