Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Activated PI3K

Publication date: Available online 18 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Tsubasa Okano, Kohsuke Imai, Yuki Tsujita, Noriko Mitsuiki, Kenichi Yoshida, Chikako Kamae, Kenichi Honma, Kanako Mitsui-Sekinaka, Yujin Sekinaka, Tamaki Kato, Katsuyuki Hanabusa, Eri Endo, Takehiro Takashima, Haruka Hiroki, Tzu-Wen Yeh, Keisuke Tanaka, Masakazu Nagahori, Ikuya Tsuge, Yuki Bando, Fuminori Iwasaki, Yoshiaki Shikama, Masami Inoue, Tomiko Kimoto, Naohiko Moriguchi, Yuki Yuza, Takashi Kaneko, Kyoko Suzuki, Tomoyo Matsubara, Yoshihiro Maruo, Tomoaki Kunitsu, Tomoko Waragai, Hideki Sano, Yuko Hashimoto, Kazuhiro Tasaki, Osamu Suzuki, Toshihiko Shirakawa, Motohiro Kato, Toru Uchiyama, Masataka Ishimura, Tetsuzo Tauchi, Hiroshi Yagasaki, Shiann-Tarng Jou, Hsin-Hui Yu, Hirokazu Kanegane, Sven Kracker, Anne Durandy, Daiei Kojima, Hideki Muramatsu, Taizo Wada, Yuzaburo Inoue, Hidetoshi Takada, Seiji Kojima, Seishi Ogawa, Osamu Ohara, Shigeaki Nonoyama, Tomohiro Morio
BackgroundActivated phosphatidylinositol-3-OH kinase-delta (PI3Kδ) syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory infections, lymphoid hyperplasia, and herpesviridae infections due to germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) may be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, method, and outcomes of HSCT for APDS1 remain undefined.ObjectiveOur objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT.MethodsWe retrospectively reviewed the medical records of cohorts undergoing HSCT at collaborating facilities.ResultsThirty-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 (RIC). Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT.ConclusionPatients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based RIC-HSCT ameliorated clinical symptoms, but transplant-related complications were frequent, including graft failure.

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Teaser

Clinical analysis of 23 patients with APDS1 revealed poor long-term event-free survival (39.6%) with a broad spectrum of clinical manifestations. Fludarabine-based RIC-HSCT could be an effective treatment, but complications and engraftment failure were frequent.


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