Recent Advances in Transplantation for Primary Immune Deficiency Diseases: A Comprehensive Review

Abstract

Hematopoietic cell transplantation (HCT) is a curative therapeutic option for severe combined immunodeficiency (SCID), a group of diseases which otherwise carry life expectancies that are of limited duration and quality. Survival following HCT for SCID has improved from approximately 23 to 91 % over the last 40 years. Success with SCID prompted efforts to apply HCT to the therapeutic challenge of well over 20 molecularly defined primary immune deficiency diseases (PID). Such success is due to both early recognition of PIDs and advances in the field of transplantation. Such advances include high-resolution HLA DNA donor-recipient matching, expansion of donor sources, better tolerated conditioning, new antibiotics, and wider availability. International collaborative efforts have provided patients and caregivers information that permit better treatment decisions now, and direct clinicians and investigators to ensure progress in the future. Pioneers in screening for SCID have taken steps to correct the fundamental challenge to successful treatment, which is the rapid discovery and characterization of cases and offering the transplant option to an affected child early in life; blood spot testing for T and B cell receptor quantification is now available to a growing fraction of newborns. Organizations including the Primary Immune Deficiency Treatment Consortium in the USA, The European Society for Primary Immunodeficiency, the European Group for Blood and Marrow Transplantation, the Pediatric Blood and Marrow Transplant Consortium, the United States Immunodeficiency Network, the Immune Deficiency Foundation, and the Jeffrey Modell Foundation are contributing mightily to increase awareness and standardize optimal utilization to the benefit of patients. This review will update the allergist-immunologist concerning disease presentations, indications for transplantation, methodologies, conditioning regimens, and clinical outcomes for patients with PID for which timely HCT is critical.

Periodontal and other oral manifestations of immunodeficiency diseases

“…Survival after HCT with HLA-identical donors has been reported to be over 92% (Grunebaum et al, 2006). In candidate patients for transplantation, HCT therapy has increased the survival rates for patients with SCID from 23% to over 90% in the last 40 years (de la Morena and Nelson, 2014). Highresolution DNA donor-recipient matching and enhanced conditioning regimens have contributed to these therapeutic achievements.…”

Primary immunodeficiency in Africa – a review

“…[19,23,24] An allogeneic HSCT involves the intravenous infusion of allogeneic haematopoietic stem cells into the recipient's body usually after preparation of the recipient with a conditioning regimen, which permits some degree of donor cell engraftment and replacement of lymphohaematopoietic function. [26] This procedure was first performed in 1968 on a 22-month-old male infant suffering from SCID. [25] In the past 45 years, there have been great advances in the field of HSCT.…”

“…[25] In the past 45 years, there have been great advances in the field of HSCT. [26] The remarkable improvements in allogeneic HSCT, despite the limitations of HSCT, e.g. the lack of human leukocyte antigen (HLA)-compatible donors and also complications such as graft-versus-host disease (GVHD), have increased interest in gene therapy for treating PID patients.…”

The CD11a and Endothelial Protein C Receptor Marker Combination Simplifies and Improves the Purification of Mouse Hematopoietic Stem Cells

“…Successful HSC transplantation (HSCT) can potentially treat any disorder inherent to the hematopoietic system by ablation of the defective blood system followed by reconstitution by healthy donor HSCs 2. However, HSCT is reserved only for high‐risk patients due to the dangers of HSCT‐related complications, including graft rejection, graft failure, and Graft‐versus‐Host Disease 2. Transplantation of sufficient numbers of pure HSCs can bypass many of these HSCT‐related complications 3, 4, 5.…”