Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency

Abstract

Hematopoietic stem cell transplantation (HSCT) is an effective approach for the treatment of severe combined immunodeficiency (SCID). However, SCID is not a homogeneous disease, and the treatment required for successful transplantation varies significantly between SCID subtypes and the degree of HLA mismatch between the best available donor and the patient. Recent studies are beginning to more clearly define this heterogeneity and how outcomes may vary. With a more detailed understanding of SCID, new approaches can be developed to maximize immune reconstitution, while minimizing acute and long-term toxicities associated with chemotherapy conditioning.

Conflict of interest statement

Compliance with Ethics Guidelines: Conflicts of Interest: Justin T. Wahlstrom and Christopher C. Dvorak declare that they have no conflict of interest.

Figures

Figure 1

Donor selection and conditioning regimen in patients with typical SCID (UCSF approach). 1Algorithm excludes Omenn's syndrome and leaky SCID that would be classified as atypical (2). Also excludes patients with DNA sensitivity, as donor selection and conditioning for these patients are variable due to the high risk of rejection and potential for chemotherapy toxicity 2Based on availability, CMV status, donor age, or other variables. Patients with RAG SCID receiving a haploidentical transplant will generally require non-myeloablative chemotherapy and serotherapy. 3May consider chemotherapy-based conditioning for enhanced B cell and/or T cell reconstitution 4Patients with T-B-NK+ SCID receiving an URD transplant generally require a conditioning regimen with serotherapy 5Experimental gene therapy protocols are becoming more widely available and should be considered in cases where no appropriate donor can be identified