Dimitrova, D;
Nademi, Z;
Maccari, ME;
Ehl, S;
Uzel, G;
Tomoda, T;
Okano, T;
... Kanakry, JA; + view all
(2021)
International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.
Journal of Allergy and Clinical Immunology
10.1016/j.jaci.2021.04.036.
(In press).
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Abstract
BACKGROUND: Activated phosphoinositide 3-kinase (PI3K) delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT). OBJECTIVE: We sought to characterize HCT outcomes in APDS. METHODS: Retrospective data was collected on 57 APDS1/2 patients (median age 13 years, range 2-66) who underwent HCT. RESULTS: Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With 2.3 years median follow-up, 2-year overall and graft failure-free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 vs 2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mTOR inhibitors (mTORi) were used in the first year post-HCT, compared to 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 non-immunologic roles of PI3K 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.
| Type: | Article |
|---|---|
| Title: | International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jaci.2021.04.036 |
| Publisher version: | https://doi.org/10.1016/j.jaci.2021.04.036 |
| Language: | English |
| Additional information: | © 2021 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Primary immunodeficiency, activated phosphoinositide 3-kinase delta syndrome, allogeneic hematopoietic cell transplantation, graft failure, lymphoproliferation, mTOR inhibitor, serotherapy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10129310 |
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