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.

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