Use of TCR α+β+/CD19+-Depleted Haploidentical Hematopoietic Stem Cell Transplant Is a Viable Option in Patients With Primary Immune Deficiency Without Matched Sibling Donor

J Clin Immunol. 2019 Jul;39(5):505-511. doi: 10.1007/s10875-019-00648-x. Epub 2019 Jun 6.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with primary immune deficiency (PID). Haploidentical donors have historically been associated with higher rates of graft-versus-host disease (GvHD) and graft failure. Use of T cell receptor (TCR) α+β+/CD19+-depleted grafts has resulted in improved haploidentical HSCT outcomes. We sought to evaluate outcomes of TCR α+β+/CD19+-depleted haploidentical HSCT in pediatric patients with PID at a single center in Australia. Specifically, we evaluated immune reconstitution, looking at time to T cell and B cell reconstitution, and B cell function post-HSCT. Eleven patients with a mean age of 7.92 years (range 0.33-17.17 years) were included. The median time to B cell recovery was 93 days (range 41-205 days), and the median time to cessation of immunoglobulin replacement was 281.5 days (range 41-205 days). All patients who had ceased immunoglobulin replacement had an adequate response to pneumococcal conjugate (Prevenar 13) vaccine. The median time to CD4+ recovery was 132 days (range 30-296 days), and naive T cells were present in all surviving patients by 4 months post-HSCT. Eight of 11 patients are surviving, with six patients having whole blood chimerism greater than 95%, one patient with whole blood chimerism of 82.8%, and another with 76.0%. All of these patients clinically had no evidence of underlying immunodeficiency. Likelihood of overall survival at 2 years post-HSCT was 81.8%. Cumulative incidence of acute GvHD was 27.3%. Cumulative incidence of CMV viremia was 63.6%. All patients previously exposed to CMV had reactivation post-HSCT, but were controlled with pre-emptive CMV treatment. Assuming most children with PID have a haploidentical donor available, use of this technique is likely to result in good outcomes for patients who do not have a suitable matched sibling or matched unrelated donor.

Keywords: Immune reconstitution; Primary immune deficiency; TCR α+β+/CD19+–depleted haploidentical HSCT.

MeSH terms

  • Adolescent
  • Antigens, CD19
  • B-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Male
  • Primary Immunodeficiency Diseases / immunology
  • Primary Immunodeficiency Diseases / therapy*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Siblings
  • T-Lymphocytes / immunology
  • Tissue Donors

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell, alpha-beta