{"doi":"10.1016/j.jaci.2021.04.036","title":"International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome","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.","journal":"Journal of Allergy and Clinical Immunology","year":2021,"id":152914,"datarank":2.332156970995282,"base_score":4.290459441148391,"endowment":4.290459441148391,"self_citation_contribution":0.6435689161722588,"citation_network_contribution":1.688588054823023,"self_endowment_contribution":0.6435689161722588,"citer_contribution":1.688588054823023,"corpus_percentile":90.85634718032026,"corpus_rank":1183,"citation_count":72,"citer_count":54,"citers_with_citation_signal":40,"citers_with_endowment":40,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7177,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":649220,"name":"Zohreh Nademi","orcid":"0000-0002-3874-2646","position":1,"is_corresponding":false},{"id":641850,"name":"Maria Elena Maccari","orcid":"0000-0001-6488-7622","position":2,"is_corresponding":false},{"id":641864,"name":"Stephan Ehl","orcid":"0000-0002-9265-2721","position":3,"is_corresponding":false},{"id":295452,"name":"Gülbû Uzel","orcid":"0000-0002-3942-1086","position":4,"is_corresponding":false},{"id":650431,"name":"Takahiro Tomoda","orcid":null,"position":5,"is_corresponding":false},{"id":649221,"name":"Tsubasa Okano","orcid":"0000-0001-6769-7402","position":6,"is_corresponding":false},{"id":649222,"name":"Kohsuke Imai","orcid":"0000-0003-2132-8403","position":7,"is_corresponding":false},{"id":243500,"name":"Benjamin Carpenter","orcid":null,"position":8,"is_corresponding":false},{"id":649223,"name":"Winnie Ip","orcid":"0000-0002-1550-4856","position":9,"is_corresponding":false},{"id":649224,"name":"Kanchan Rao","orcid":"0000-0001-9449-8476","position":10,"is_corresponding":false},{"id":281908,"name":"Austen Worth","orcid":"0000-0001-6803-7385","position":11,"is_corresponding":false},{"id":649225,"name":"Alexandra Laberko","orcid":"0000-0002-2354-2588","position":12,"is_corresponding":false},{"id":647553,"name":"Anna Mukhinа","orcid":"0000-0002-3305-1694","position":13,"is_corresponding":false},{"id":281907,"name":"Bénédicte Neven","orcid":"0000-0001-8941-0935","position":14,"is_corresponding":false},{"id":381042,"name":"Despina Moshous","orcid":"0000-0001-6719-3693","position":15,"is_corresponding":false},{"id":649226,"name":"Carsten Speckmann","orcid":"0000-0002-6217-1556","position":16,"is_corresponding":false},{"id":285426,"name":"Klaus Warnatz","orcid":"0000-0002-1172-865X","position":17,"is_corresponding":false},{"id":649227,"name":"Claudia Wehr","orcid":"0000-0002-5037-6175","position":18,"is_corresponding":false},{"id":48203,"name":"Hassan Abolhassani","orcid":"0000-0002-4838-0407","position":19,"is_corresponding":false},{"id":281916,"name":"Asghar Aghamohammadi","orcid":"0000-0002-9454-1603","position":20,"is_corresponding":false},{"id":650432,"name":"Jacob J. 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