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Journal of Clinical Immunology

, Volume 37, Issue 6, pp 582–591 | Cite as

Long-Term Outcome of Adenosine Deaminase-Deficient Patients—a Single-Center Experience

  • Ori Scott
  • Vy Hong-Diep Kim
  • Brenda Reid
  • Anne Pham-Huy
  • Adelle R. Atkinson
  • Alessandro Aiuti
  • Eyal Grunebaum
Original Article

Abstract

Purpose

Inherited defects in the adenosine deaminase (ADA) enzyme can cause severe combined immune deficiency (SCID) and systemic abnormalities. Management options for ADA-deficient patients include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we describe the long-term benefits of these treatments.

Methods

Survival, infections, systemic sequelae, and laboratory assessments were recorded for all ADA-deficient SCID patients, managed at a single center since 1985, who survived 5 or more years following treatment.

Results

Of 20 ADA-deficient patients, the 8 (40%) who survived 5 or more years (range 6–29.5 years, median 14 years) were included in the study. Among the long-term survivors, two patients were treated exclusively with ERT, five underwent HSCT (three from HLA-matched sibling donors, two from HLA-mismatched related donors), and one received GT. The long-term survivors often suffered from recurrent respiratory infections; however, opportunistic infections occurred in only one patient. Systemic sequelae included lung disease such as bronchiectasis and asthma (four patients), neurologic abnormalities (six patients), metabolic disturbances (two patients), allergy and autoimmunity (six patients), and neoplasms (three patients). Normal CD4+ T cell numbers and function, as well as antibody production, were usually observed after HSCT and GT, but not after ERT. Late deaths occurred in two patients at 15 and 25 years after HSCT, respectively, and were attributed to respiratory failure.

Conclusions

ADA-deficient patients commonly suffer from long-term complications, emphasizing the need for improved management and for multi-disciplinary follow-up.

Keywords

Immune deficiency adenosine deaminase bone marrow transplant enzyme replacement gene therapy PEG-ADA 

Abbreviations

ADA

Adenosine deaminase

Bu

Busulfan

Cy

Cyclophosphamide

dAXP

Total deoxyadenosine nucleotides

ERT

Enzyme replacement therapy

GT

Gene therapy

HSCT

Hematopoietic stem cell transplant

IVIG

Intravenous immunoglobulin

MMRD

HLA-mismatched related donors

MMUD

HLA-mismatched donors

MSD

HLA-matched sibling donor

MUD

HLA-matched unrelated donors

SCID

Severe combined immune deficiency

Notes

Acknowledgements

The authors thank Dr. Chaim M. Roifman for his contributions to the diagnosis and management of the patients as well as the development of this manuscript. This work was supported in part by The Donald and Audrey Campbell Chair for Immunology (EG).

Compliance with Ethical Standards

Conflict of Interest

AA is the principal investigator of the ADA-SCID gene therapy clinical trial with gamma-RV; the gene therapy was licensed to GlaxoSmithKline (GSK) in 2010 and GSK became the financial sponsor of the clinical trial. Other authors disclose no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Ori Scott
    • 1
    • 2
  • Vy Hong-Diep Kim
    • 1
    • 2
  • Brenda Reid
    • 1
    • 2
  • Anne Pham-Huy
    • 3
  • Adelle R. Atkinson
    • 1
    • 2
  • Alessandro Aiuti
    • 4
    • 5
  • Eyal Grunebaum
    • 1
    • 2
    • 6
  1. 1.Division of Immunology and AllergyHospital for Sick ChildrenTorontoCanada
  2. 2.Department of PediatricsUniversity of TorontoTorontoCanada
  3. 3.Division of Pediatric Infectious DiseasesChildren’s Hospital of Eastern OntarioOttawaCanada
  4. 4.San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) and Pediatric ImmunohematologyIRCCS San Raffaele Scientific InstituteMilanItaly
  5. 5.Vita Salute San Raffaele UniversityMilanItaly
  6. 6.Developmental and Stem Cell Biology ProgramHospital for Sick ChildrenTorontoCanada

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