Dataset Information
International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.
Ontology highlight
ABSTRACT: Background
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.
SUBMITTER: Dimitrova D
PROVIDER: S-EPMC8611111 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.
The Journal of allergy and clinical immunology 20210524 1
<h4>Background</h4>Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).<h4>Objectives</h4>This study sought to characterize HCT outcomes in APDS.<h4>Methods</h4>Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.<h4>Results</h4>Pre-HCT comorbidities such as lung, gastrointestinal, an ...[more]