학술논문
International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.
Document Type
article
Author
Dimitrova, Dimana; Nademi, Zohreh; Maccari, Maria Elena; Ehl, Stephan; Uzel, Gulbu; Tomoda, Takahiro; Okano, Tsubasa; Imai, Kohsuke; Carpenter, Benjamin; Ip, Winnie; Rao, Kanchan; Worth, Austen JJ; Laberko, Alexandra; Mukhina, Anna; Néven, Bénédicte; Moshous, Despina; Speckmann, Carsten; Warnatz, Klaus; Wehr, Claudia; Abolhassani, Hassan; Aghamohammadi, Asghar; Bleesing, Jacob J; Dara, Jasmeen; Dvorak, Christopher C; Ghosh, Sujal; Kang, Hyoung Jin; Markelj, Gašper; Modi, Arunkumar; Bayer, Diana K; Notarangelo, Luigi D; Schulz, Ansgar; Garcia-Prat, Marina; Soler-Palacín, Pere; Karakükcü, Musa; Yilmaz, Ebru; Gambineri, Eleonora; Menconi, Mariacristina; Masmas, Tania N; Holm, Mette; Bonfim, Carmem; Prando, Carolina; Hughes, Stephen; Jolles, Stephen; Morris, Emma C; Kapoor, Neena; Koltan, Sylwia; Paneesha, Shankara; Steward, Colin; Wynn, Robert; Duffner, Ulrich; Gennery, Andrew R; Lankester, Arjan C; Slatter, Mary; Kanakry, Jennifer A
Source
The Journal of allergy and clinical immunology. 149(1)
Subject
Language
Abstract
BackgroundActivated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).ObjectivesThis study sought to characterize HCT outcomes in APDS.MethodsRetrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.ResultsPre-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.ConclusionsGraft 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.