Long term outcomes of severe combined immunodeficiency: therapy implications

Expert Rev Clin Immunol. 2017 Nov;13(11):1029-1040. doi: 10.1080/1744666X.2017.1381558. Epub 2017 Sep 23.

Abstract

Newborn screening has led to a better understanding of the prevalence of Severe Combined Immunodeficiency (SCID) overall and in terms of specific genotypes. Survival has improved following hematopoietic stem cell transplantation (HCT) with the best outcomes seen following use of a matched sibling donor. However, questions remain regarding the optimal alternative donor source, appropriate use of conditioning and the impact of these decisions on immune reconstitution and other late morbidities. Areas covered: The currently available literature reporting late effects after HCT for SCID and use of alternative therapies including enzyme replacement, alternative donors and gene therapy are reviewed. A literature search was performed on Pubmed and ClinicalTrials.gov using key words 'Severe Combined Immunodeficiency', 'SCID', 'hematopoietic stem cell transplant', 'conditioning', 'gene therapy', 'SCID newborn screening', 'TREC' and 'late effects'. Expert commentary: Newborn screening has dramatically changed the clinical presentation of newborn SCID. While the majority of patients with SCID survive HCT, data regarding late effects in these patients is limited and additional studies focused on genotype specific late effects are needed. Prospective studies aimed at minimizing the use of alkylating agents and reducing late effects beyond survival are needed. Gene therapy is being developed and will likely become a more commonly used treatment that will require separate consideration of survival and late effects.

Keywords: Hematopoietic Stem Cell Transplant (HCT); Newborn Screening (NBS); RAG SCID; Radiosensitive SCID (RS-SCID); Severe Combined Immunodeficiency (SCID); TREC; XSCID; conditioning; gene therapy; late effects.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Expert Testimony
  • Genetic Therapy
  • Genotype*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant, Newborn
  • Neonatal Screening
  • Severe Combined Immunodeficiency / diagnosis
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / therapy*
  • Transplantation Conditioning
  • Treatment Outcome