Tsubasa Okano1, Kohsuke Imai2, Yuki Tsujita3, Noriko Mitsuiki1, Kenichi Yoshida4, Chikako Kamae3, Kenichi Honma3, Kanako Mitsui-Sekinaka3, Yujin Sekinaka3, Tamaki Kato3, Katsuyuki Hanabusa1, Eri Endo1, Takehiro Takashima1, Haruka Hiroki1, Tzu-Wen Yeh1, Keisuke Tanaka1, Masakazu Nagahori5, Ikuya Tsuge6, Yuki Bando7, Fuminori Iwasaki8, Yoshiaki Shikama9, Masami Inoue10, Tomiko Kimoto10, Naohiko Moriguchi11, Yuki Yuza12, Takashi Kaneko12, Kyoko Suzuki13, Tomoyo Matsubara13, Yoshihiro Maruo14, Tomoaki Kunitsu14, Tomoko Waragai15, Hideki Sano16, Yuko Hashimoto17, Kazuhiro Tasaki17, Osamu Suzuki17, Toshihiko Shirakawa18, Motohiro Kato19, Toru Uchiyama20, Masataka Ishimura21, Tetsuzo Tauchi22, Hiroshi Yagasaki23, Shiann-Tarng Jou24, Hsin-Hui Yu24, Hirokazu Kanegane1, Sven Kracker25, Anne Durandy25, Daiei Kojima26, Hideki Muramatsu26, Taizo Wada27, Yuzaburo Inoue28, Hidetoshi Takada29, Seiji Kojima26, Seishi Ogawa4, Osamu Ohara30, Shigeaki Nonoyama3, Tomohiro Morio1. 1. Department of Pediatrics, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. 2. Department of Pediatrics, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address: kimai.ped@tmd.ac.jp. 3. Department of Pediatrics, National Defense Medical College, Saitama, Japan. 4. Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 5. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. 6. Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, Japan. 7. Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan. 8. Division of Hemato-Oncology Regenerative Medicine, Yokohama, Japan. 9. Division of Infectious Disease and Immunology, Kanagawa Children's Medical Center, Yokohama, Japan. 10. Department of Hematology/Oncology, Osaka Women's and Children's Hospital, Osaka, Japan. 11. Department of Pediatrics, Kindai University Sakai Hospital, Sakai, Japan. 12. Department of Hematology/Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 13. Department of Pediatrics, Juntendo University, Urayasu Hospital, Chiba, Japan. 14. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan. 15. Department of Pediatrics, Fukushima Medical University, Fukushima, Japan. 16. Department of Pediatric Oncology, Fukushima Medical University, Fukushima, Japan. 17. Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan. 18. Department of Pediatrics, Nagasaki University Hospital, Nagasaki, Japan. 19. Division of Transplantation and Cell Therapy, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan. 20. Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan. 21. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 22. Department of Hematology, Tokyo Medical University, Tokyo, Japan. 23. Department of Pediatrics, Nihon University Itabashi Hospital, Tokyo, Japan. 24. Department of Pediatrics, National Taiwan University Children's Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. 25. Université Paris Descartes, Sorbonne Paris Cité, Imagine Institute, INSERM UMR 1163, Human Lymphohematopoiesis Laboratory, Paris, France. 26. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. 27. Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. 28. Department of Pediatrics, Eastern Chiba Medical Center, Togane, Chiba, Japan. 29. Department of Perinatal and Pediatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 30. Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
Abstract
BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.
BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION:Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.
Authors: Stuart G Tangye; Julia Bier; Anthony Lau; Tina Nguyen; Gulbu Uzel; Elissa K Deenick Journal: J Clin Immunol Date: 2019-03-25 Impact factor: 8.317
Authors: Dimana Dimitrova; Juan Gea-Banacloche; Seth M Steinberg; Jennifer L Sadler; Stephanie N Hicks; Ellen Carroll; Jennifer S Wilder; Mark Parta; Lauren Skeffington; Thomas E Hughes; Jenny E Blau; Miranda M Broadney; Jeremy J Rose; Amy P Hsu; Rochelle Fletcher; Natalia S Nunes; Xiao-Yi Yan; William G Telford; Veena Kapoor; Jeffrey I Cohen; Alexandra F Freeman; Elizabeth Garabedian; Steven M Holland; Andrea Lisco; Harry L Malech; Luigi D Notarangelo; Irini Sereti; Nirali N Shah; Gulbu Uzel; Christa S Zerbe; Daniel H Fowler; Ronald E Gress; Christopher G Kanakry; Jennifer A Kanakry Journal: Biol Blood Marrow Transplant Date: 2019-09-04 Impact factor: 5.742
Authors: Stephen A Schworer; Olivia L Francis; Steven M Johnson; Benjamin D Smith; Stuart H Gold; Andrew B Smitherman; Eveline Y Wu Journal: J Pediatr Hematol Oncol Date: 2021-11-01 Impact factor: 1.289