Journal article
International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome
Journal of allergy and clinical immunology, Vol.149(1), pp.410-421.e7
01/01/2022
DOI: 10.1016/j.jaci.2021.04.036
PMCID: PMC8611111
PMID: 34033842
Abstract
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).
This study sought to characterize HCT outcomes in APDS.
Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.
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.
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.
Details
- Title: Subtitle
- International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome
- Creators
- Dimana Dimitrova - National Institutes of HealthZohreh Nademi - Newcastle UniversityMaria Elena Maccari - University Medical Center FreiburgStephan Ehl - University Medical Center FreiburgGulbu Uzel - National Institute of Allergy and Infectious DiseasesTakahiro Tomoda - Tokyo Medical and Dental UniversityTsubasa Okano - Tokyo Medical and Dental UniversityKohsuke Imai - Tokyo Medical and Dental UniversityBenjamin Carpenter - National Health ServiceWinnie Ip - Great Ormond Street HospitalKanchan Rao - Great Ormond Street Hospital for Children NHS Foundation TrustAusten J.J. Worth - Great Ormond Street HospitalAlexandra Laberko - Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and ImmunologyAnna Mukhina - Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, RussiaBénédicte Néven - Hôpital Necker-Enfants MaladesDespina Moshous - Hôpital Necker-Enfants MaladesCarsten Speckmann - University Medical Center FreiburgKlaus Warnatz - University of FreiburgClaudia Wehr - University of FreiburgHassan Abolhassani - Tehran University of Medical SciencesAsghar Aghamohammadi - Tehran University of Medical SciencesJacob J. Bleesing - Cincinnati Children's Hospital Medical CenterJasmeen Dara - UCSF Benioff Children's HospitalChristopher C. Dvorak - University of California, San FranciscoSujal Ghosh - Heinrich Heine University DüsseldorfHyoung Jin Kang - Seoul National UniversityGašper Markelj - Ljubljana University Medical CentreArunkumar Modi - University of Arkansas for Medical SciencesDiana K. Bayer - University of IowaLuigi D. Notarangelo - National Institute of Allergy and Infectious DiseasesAnsgar Schulz - Department of Pediatrics, University Medical Center Ulm, Ulm, GermanyMarina Garcia-Prat - Vall d'Hebron Hospital UniversitariPere Soler-Palacín - Vall d'Hebron Hospital UniversitariMusa Karakükcü - Erciyes UniversityEbru Yilmaz - Erciyes UniversityEleonora Gambineri - University of FlorenceMariacristina Menconi - Azienda Ospedaliera Universitaria PisanaTania N. Masmas - Copenhagen University HospitalMette Holm - Aarhus University HospitalCarmem Bonfim - Hospital Erasto GaertnerCarolina Prando - Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, BrazilStephen Hughes - Royal Manchester Children's HospitalStephen Jolles - University Hospital of WalesEmma C. Morris - University College LondonNeena Kapoor - Children's Hospital of Los AngelesSylwia Koltan - Nicolaus Copernicus UniversityShankara Paneesha - Heartlands HospitalColin Steward - University of BristolRobert Wynn - Royal Manchester Children's HospitalUlrich Duffner - Michigan State UniversityAndrew R. Gennery - Newcastle UniversityArjan C. Lankester - Leiden University Medical CenterMary Slatter - Newcastle UniversityJennifer A. Kanakry - National Institutes of Health
- Resource Type
- Journal article
- Publication Details
- Journal of allergy and clinical immunology, Vol.149(1), pp.410-421.e7
- DOI
- 10.1016/j.jaci.2021.04.036
- PMID
- 34033842
- PMCID
- PMC8611111
- NLM abbreviation
- J Allergy Clin Immunol
- ISSN
- 0091-6749
- eISSN
- 1097-6825
- Publisher
- Elsevier Inc
- Grant note
- National Institutes of Health (https://doi.org/10.13039/100000002) Intramural Program of the National Cancer Institute
- Language
- English
- Date published
- 01/01/2022
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology; Internal Medicine
- Record Identifier
- 9984695830702771
Metrics
7 Record Views