Long-term immune reconstitution after anti-CD52–treated or anti-CD34–treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency

Abstract

Results of treatment of severe T-lymphocyte immunodeficiencies by means of hematopoietic stem cell (HSC) transplantation have improved. T cell-depleted haploidentical transplantations are successful if there is no HLA-identical donor. Methods to remove T lymphocytes include addition of anti-CD52 antibodies and CD34(+) HSC selection. Assessment of long-term immune function is important after these treatments. We looked at immune reconstitution in 36 survivors for more than 2 years after HSC transplantation for severe T-lymphocyte immunodeficiencies and compared engraftment quality between the 2 T-lymphocyte depletion methods. Chimerism, T- and B-lymphocyte subsets, immunoglobulin levels, and specific antibody production at last follow-up were examined. The chi(2) (Fisher exact test) and Wilcoxon rank sum analyses were used to compare the groups. Nineteen patients received anti-CD52-treated and 19 anti-CD34-treated HSCs. More anti-CD52-treated patients had full donor myeloid chimerism (P = .025). All patients had full donor T-lymphocyte chimerism. There was no difference in donor B-lymphocyte chimerism, but significantly more anti-CD52-treated patients had class-switched memory B lymphocytes (P = .024), normal IgG levels, and normal responses to tetanus and Haemophilus influenzae type B vaccination. More anti-CD52-treated patients with common gamma chain or Janus-associated kinase 3 severe combined immunodeficiency had donor B lymphocytes. Long-term T-lymphocyte function is good with either treatment method, with a low incidence of graft-versus-host disease. The results imply more incomplete donor chimerism in anti-CD34-treated patients with less B-lymphocyte function.