HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >

Outcomes in Two Japanese Adenosine Deaminase-Deficiency Patients Treated by Stem Cell Gene Therapy with No Cytoreductive Conditioning

Files in This Item:
manuscript.pdf5.16 MBPDFView/Open
Please use this identifier to cite or link to this item:

Title: Outcomes in Two Japanese Adenosine Deaminase-Deficiency Patients Treated by Stem Cell Gene Therapy with No Cytoreductive Conditioning
Authors: Otsu, Makoto Browse this author →KAKEN DB
Yamada, Masafumi Browse this author
Nakajima, Satoru Browse this author
Kida, Miyuki Browse this author →KAKEN DB
Maeyama, Yoshihiro Browse this author
Hatano, Norikazu Browse this author
Toita, Nariaki Browse this author
Takezaki, Shunichiro Browse this author
Okura, Yuka Browse this author
Kobayashi, Ryoji Browse this author
Matsumoto, Yoshinori Browse this author
Tatsuzawa, Osamu Browse this author
Tsuchida, Fumiko Browse this author
Kato, Shunichi Browse this author →KAKEN DB
Kitagawa, Masanari Browse this author
Mineno, Junichi Browse this author
Hershfield, Michael S. Browse this author
Bali, Pawan Browse this author
Candotti, Fabio Browse this author
Onodera, Masafumi Browse this author →KAKEN DB
Kawamura, Nobuaki Browse this author →KAKEN DB
Sakiyama, Yukio Browse this author →KAKEN DB
Ariga, Tadashi Browse this author →KAKEN DB
Keywords: Gene therapy
adenosine deaminase (ADA)
severe combined immunodeficiency (SCID)
primary immunodeficiency (PID)
retroviral vector(s)
hematopoietic stem cell(s)
Issue Date: May-2015
Publisher: Springer
Journal Title: Journal of clinical immunology
Volume: 35
Issue: 4
Start Page: 384
End Page: 398
Publisher DOI: 10.1007/s10875-015-0157-1
Abstract: Objective We here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical trials, its results provide insights into SCGT for ADA deficiency. Patients and Methods Pt 1 was treated at age 4.7 years, whereas pt 2, who had previously received T-cell gene therapy, was treated at age 13 years. Bone marrow CD34(+) cells were harvested after enzyme replacement therapy (ERT) was withdrawn; following transduction of ADA cDNA by the gamma-retroviral vector GCsapM-ADA, they were administered intravenously. No cytoreductive conditioning, at present considered critical for therapeutic benefit, was given before cell infusion. Hematological/immunological reconstitution kinetics, levels of systemic detoxification, gene-marking levels, and proviral insertion sites in hematopoietic cells were assessed. Results Treatment was well tolerated, and no serious adverse events were observed. Engraftment of gene-modified repopulating cells was evidenced by the appearance and maintenance of peripheral lymphocytes expressing functional ADA. Systemic detoxification was moderately achieved, allowing temporary discontinuation of ERT for 6 and 10 years in pt 1 and pt 2, respectively. Recovery of immunity remained partial, with lymphocyte counts in pts 1 and 2, peaked at 408/mm(3) and 1248/mm(3), approximately 2 and 5 years after SCGT. Vector integration site analyses confirmed that hematopoiesis was reconstituted with a limited number of clones, some of which were shown to have myelo-lymphoid potential. Conclusions Outcomes in SCGT for ADA-SCID are described in the context of a unique protocol, which used neither ERT nor cytoreductive conditioning. Although proven safe, immune reconstitution was partial and temporary. Our results reiterate the importance of cytoreductive conditioning to ensure greater benefits from SCGT.
Rights: The final publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 有賀 正

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


Feedback - Hokkaido University