Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1

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 IwasakiYoshiaki 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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)266-275
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume143
Issue number1
DOIs
Publication statusPublished - Jan 2019

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Hematopoietic Stem Cell Transplantation
Phosphatidylinositol 3-Kinases
Herpesviridae Infections
Respiratory Tract Infections
Disease-Free Survival
Hyperplasia
Medical Records
Transplantation
Transplants
Mutation
Survival
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1. / Okano, Tsubasa; Imai, Kohsuke; Tsujita, Yuki; Mitsuiki, Noriko; Yoshida, Kenichi; Kamae, Chikako; Honma, Kenichi; Mitsui-Sekinaka, Kanako; Sekinaka, Yujin; Kato, Tamaki; Hanabusa, Katsuyuki; Endo, Eri; Takashima, Takehiro; Hiroki, Haruka; Yeh, Tzu Wen; Tanaka, Keisuke; Nagahori, Masakazu; Tsuge, Ikuya; Bando, Yuki; Iwasaki, Fuminori; Shikama, Yoshiaki; Inoue, Masami; Kimoto, Tomiko; Moriguchi, Naohiko; Yuza, Yuki; Kaneko, Takashi; Suzuki, Kyoko; Matsubara, Tomoyo; Maruo, Yoshihiro; Kunitsu, Tomoaki; Waragai, Tomoko; Sano, Hideki; Hashimoto, Yuko; Tasaki, Kazuhiro; Suzuki, Osamu; Shirakawa, Toshihiko; Kato, Motohiro; Uchiyama, Toru; Ishimura, Masataka; Tauchi, Tetsuzo; Yagasaki, Hiroshi; Jou, Shiann Tarng; Yu, Hsin Hui; Kanegane, Hirokazu; Kracker, Sven; Durandy, Anne; Kojima, Daiei; Muramatsu, Hideki; Wada, Taizo; Inoue, Yuzaburo; Takada, Hidetoshi; Kojima, Seiji; Ogawa, Seishi; Ohara, Osamu; Nonoyama, Shigeaki; Morio, Tomohiro.

In: Journal of Allergy and Clinical Immunology, Vol. 143, No. 1, 01.2019, p. 266-275.

Research output: Contribution to journalArticle

Okano, T, Imai, K, Tsujita, Y, Mitsuiki, N, Yoshida, K, Kamae, C, Honma, K, Mitsui-Sekinaka, K, Sekinaka, Y, Kato, T, Hanabusa, K, Endo, E, Takashima, T, Hiroki, H, Yeh, TW, Tanaka, K, Nagahori, M, Tsuge, I, Bando, Y, Iwasaki, F, Shikama, Y, Inoue, M, Kimoto, T, Moriguchi, N, Yuza, Y, Kaneko, T, Suzuki, K, Matsubara, T, Maruo, Y, Kunitsu, T, Waragai, T, Sano, H, Hashimoto, Y, Tasaki, K, Suzuki, O, Shirakawa, T, Kato, M, Uchiyama, T, Ishimura, M, Tauchi, T, Yagasaki, H, Jou, ST, Yu, HH, Kanegane, H, Kracker, S, Durandy, A, Kojima, D, Muramatsu, H, Wada, T, Inoue, Y, Takada, H, Kojima, S, Ogawa, S, Ohara, O, Nonoyama, S & Morio, T 2019, 'Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1', Journal of Allergy and Clinical Immunology, vol. 143, no. 1, pp. 266-275. https://doi.org/10.1016/j.jaci.2018.04.032
Okano, Tsubasa ; Imai, Kohsuke ; Tsujita, Yuki ; Mitsuiki, Noriko ; Yoshida, Kenichi ; Kamae, Chikako ; Honma, Kenichi ; Mitsui-Sekinaka, Kanako ; Sekinaka, Yujin ; Kato, Tamaki ; Hanabusa, Katsuyuki ; Endo, Eri ; Takashima, Takehiro ; Hiroki, Haruka ; Yeh, Tzu Wen ; Tanaka, Keisuke ; Nagahori, Masakazu ; Tsuge, Ikuya ; Bando, Yuki ; Iwasaki, Fuminori ; Shikama, Yoshiaki ; Inoue, Masami ; Kimoto, Tomiko ; Moriguchi, Naohiko ; Yuza, Yuki ; Kaneko, Takashi ; Suzuki, Kyoko ; Matsubara, Tomoyo ; Maruo, Yoshihiro ; Kunitsu, Tomoaki ; Waragai, Tomoko ; Sano, Hideki ; Hashimoto, Yuko ; Tasaki, Kazuhiro ; Suzuki, Osamu ; Shirakawa, Toshihiko ; Kato, Motohiro ; Uchiyama, Toru ; Ishimura, Masataka ; Tauchi, Tetsuzo ; Yagasaki, Hiroshi ; Jou, Shiann Tarng ; Yu, Hsin Hui ; Kanegane, Hirokazu ; Kracker, Sven ; Durandy, Anne ; Kojima, Daiei ; Muramatsu, Hideki ; Wada, Taizo ; Inoue, Yuzaburo ; Takada, Hidetoshi ; Kojima, Seiji ; Ogawa, Seishi ; Ohara, Osamu ; Nonoyama, Shigeaki ; Morio, Tomohiro. / Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1. In: Journal of Allergy and Clinical Immunology. 2019 ; Vol. 143, No. 1. pp. 266-275.
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title = "Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1",
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.",
author = "Tsubasa Okano and Kohsuke Imai and Yuki Tsujita and Noriko Mitsuiki and Kenichi Yoshida and Chikako Kamae and Kenichi Honma and Kanako Mitsui-Sekinaka and Yujin Sekinaka and Tamaki Kato and Katsuyuki Hanabusa and Eri Endo and Takehiro Takashima and Haruka Hiroki and Yeh, {Tzu Wen} and Keisuke Tanaka and Masakazu Nagahori and Ikuya Tsuge and Yuki Bando and Fuminori Iwasaki and Yoshiaki Shikama and Masami Inoue and Tomiko Kimoto and Naohiko Moriguchi and Yuki Yuza and Takashi Kaneko and Kyoko Suzuki and Tomoyo Matsubara and Yoshihiro Maruo and Tomoaki Kunitsu and Tomoko Waragai and Hideki Sano and Yuko Hashimoto and Kazuhiro Tasaki and Osamu Suzuki and Toshihiko Shirakawa and Motohiro Kato and Toru Uchiyama and Masataka Ishimura and Tetsuzo Tauchi and Hiroshi Yagasaki and Jou, {Shiann Tarng} and Yu, {Hsin Hui} and Hirokazu Kanegane and Sven Kracker and Anne Durandy and Daiei Kojima and Hideki Muramatsu and Taizo Wada and Yuzaburo Inoue and Hidetoshi Takada and Seiji Kojima and Seishi Ogawa and Osamu Ohara and Shigeaki Nonoyama and Tomohiro Morio",
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journal = "Journal of Allergy and Clinical Immunology",
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T1 - Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1

AU - Okano, Tsubasa

AU - Imai, Kohsuke

AU - Tsujita, Yuki

AU - Mitsuiki, Noriko

AU - Yoshida, Kenichi

AU - Kamae, Chikako

AU - Honma, Kenichi

AU - Mitsui-Sekinaka, Kanako

AU - Sekinaka, Yujin

AU - Kato, Tamaki

AU - Hanabusa, Katsuyuki

AU - Endo, Eri

AU - Takashima, Takehiro

AU - Hiroki, Haruka

AU - Yeh, Tzu Wen

AU - Tanaka, Keisuke

AU - Nagahori, Masakazu

AU - Tsuge, Ikuya

AU - Bando, Yuki

AU - Iwasaki, Fuminori

AU - Shikama, Yoshiaki

AU - Inoue, Masami

AU - Kimoto, Tomiko

AU - Moriguchi, Naohiko

AU - Yuza, Yuki

AU - Kaneko, Takashi

AU - Suzuki, Kyoko

AU - Matsubara, Tomoyo

AU - Maruo, Yoshihiro

AU - Kunitsu, Tomoaki

AU - Waragai, Tomoko

AU - Sano, Hideki

AU - Hashimoto, Yuko

AU - Tasaki, Kazuhiro

AU - Suzuki, Osamu

AU - Shirakawa, Toshihiko

AU - Kato, Motohiro

AU - Uchiyama, Toru

AU - Ishimura, Masataka

AU - Tauchi, Tetsuzo

AU - Yagasaki, Hiroshi

AU - Jou, Shiann Tarng

AU - Yu, Hsin Hui

AU - Kanegane, Hirokazu

AU - Kracker, Sven

AU - Durandy, Anne

AU - Kojima, Daiei

AU - Muramatsu, Hideki

AU - Wada, Taizo

AU - Inoue, Yuzaburo

AU - Takada, Hidetoshi

AU - Kojima, Seiji

AU - Ogawa, Seishi

AU - Ohara, Osamu

AU - Nonoyama, Shigeaki

AU - Morio, Tomohiro

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

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