Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency

J Allergy Clin Immunol. 2019 Mar;143(3):852-863. doi: 10.1016/j.jaci.2018.08.024. Epub 2018 Sep 5.

PMID: 30194989

Donald B. Kohn, MD, Michael S. Hershfield, MD, Jennifer M. Puck, MD, Alessandro Aiuti, MD, PhD, Annaliesse Blincoe, MBChB, H. Bobby Gaspar, MD, PhD, Luigi D. Notarangelo, MD, Eyal Grunebaum, MD

Summary: In this study, currently available evidence about ADA-SCID was reviewed and a consensus management strategy was proposed. The outcomes of novel strategies should be evaluated prospectively in real life conditions for the management guidelines.

Abstract

Objective: Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined immunodeficiency (SCID), known as ADA-SCID. SCID newborn screening test can detect most affected infants while they are still asymptomatic, allowing for early therapy initiation. In this study, currently available evidence was reviewed and a consensus management strategy was proposed.

Results: In addition to the treatment of the immune deficiency of ADA-SCID, patients should be followed for specific non-infectious respiratory, neurological and biochemical complications associated with ADA deficiency. All patients should initially receive enzyme replacement therapy (ERT), followed by definitive treatment with either of two equal first line options. Allogeneic hematopoietic stem cell transplantation (HSCT) should be considered if an HLA matched sibling donor (MSD) or matched family donor (MFD) is available. Since 2000, the excellent safety and efficacy of gamma-retrovirus or lentivirus mediated autologous hematopoietic stem cell gene therapy (HSC-GT) in over 100 ADA-SCID patients has positioned HSC-GT as an equal alternative. If MSD/MFD HSCT or HSC-GT are not available or have failed, ERT can be continued or re-instituted, and HSCT using alternative donors should be considered.

Conclusion: The outcomes of novel HSCT, ERT and HSC-GT strategies should be evaluated prospectively in “real life” conditions to further inform these management guidelines.

Keywords: Adenosine deaminase deficiency, Enzyme replacement therapy, Gene therapy, Hematopoietic stem cell transplantations, Lentivirus, Severe combined immune deficiency