Chapter 8 - Immunodeficiencies and Metabolic Diseases

Abstract

Primary immune deficiencies (PID) are rare diseases, but cause significant morbidity and typically lead to early mortality. The first patient successfully treated by hematopoietic stem cell transplantation (HSCT) was an infant with severe combined immune deficiency (SCID) who received bone marrow from his human leukocyte antigen (HLA)-identical sister in 1968 (Gatti, 1968(. Since then, HSCT has become the standard of care for treatment of children with severe PID. Transplantation has the capacity to cure the majority of patients with PID, and although a stem cell graft from an unaffected matched related donor (MRD) is preferred, that option exists for only a minority of patients, leaving alternative donor stem cell sources as the choice for the majority of patients. Mismatched related donor, matched unrelated donor, and umbilical cord blood (UCB) have all been used, and outcomes vary by disease and stem cell source. The optimal stem cell source for PID patients with no available MRD is not clear (Dvorak, 2008). UCB is an attractive source for many reasons including rapid access to the donor unit allowing for (1) expedient transplant in patients at very high risk for life-threatening infection, (2) a lower risk of latent viral transmission in immunologically naïve recipients, (3) a lower risk of Graft-versus-Host Disease (GvHD) despite HLA mismatch, (4) a higher likelihood of finding an acceptable HLA-matched unit in patients who are often of ethnic minorities and/or the product of consanguinity, and (5) at least hypothetically the potential that UCB stem cells may have greater self-renewing capacity than those obtained from an adult donor (Gennery, 2007). Published studies examining the use of UCB in PID are scarce, but its use is becoming more common. PID encompasses a variety of diseases all of which are extremely rare. In this chapter, we focus on the more common disorders in this group treated with HSCT, specifically SCID and Wiskott–Aldrich syndrome.