Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1
Journal
Journal of Allergy and Clinical Immunology
Journal Volume
143
Journal Issue
1
Pages
266-275
Date Issued
2019
Author(s)
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 T.-W.
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.
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.
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. ? 2018 American Academy of Allergy, Asthma & Immunology
SDGs
Other Subjects
busulfan; cyclophosphamide; cyclosporine; etoposide; fludarabine; immunoglobulin; melphalan; methotrexate; mycophenolate mofetil; prednisolone; rapamycin; rituximab; tacrolimus; thymocyte antibody; phosphatidylinositol 4,5 bisphosphate 3 kinase; activated phosphatidylinositol 3 kinase delta syndrome type 1; adolescent; Article; child; clinical article; clinical feature; clinical outcome; cohort analysis; combined immunodeficiency; comparative study; controlled study; disease course; event free survival; female; graft failure; graft versus host reaction; hematopoietic stem cell transplantation; hepatosplenomegaly; herpes virus infection; human; immune deficiency; laboratory test; lymphocyte proliferation; lymphoid hyperplasia; male; medical record review; overall survival; plasma exchange; preschool child; priority journal; prognosis; reduced intensity conditioning; respiratory tract infection; retrospective study; school child; splenectomy; treatment indication; whole body radiation; adult; allograft; clinical trial; disease free survival; immune deficiency; immunology; lymphoproliferative disease; mortality; pathology; survival rate; Adolescent; Adult; Allografts; Child; Child, Preschool; Class I Phosphatidylinositol 3-Kinases; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Lymphoproliferative Disorders; Male; Survival Rate
Publisher
Mosby Inc.
Type
journal article