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

J Allergy Clin Immunol. 2008 Feb;121(2):361-7. doi: 10.1016/j.jaci.2007.10.035. Epub 2007 Dec 20.

Abstract

Background: 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.

Objective: 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.

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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / therapeutic use*
  • Antigens, CD / immunology*
  • Antigens, CD34 / immunology*
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes
  • CD52 Antigen
  • Glycoproteins / immunology*
  • Haemophilus Infections / prevention & control
  • Haemophilus influenzae type b
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immune System / drug effects
  • Immune System / pathology
  • Immune System / physiopathology*
  • Immunoglobulin G / blood
  • Immunologic Deficiency Syndromes / physiopathology
  • Immunologic Deficiency Syndromes / therapy*
  • Immunologic Memory
  • Infant
  • Interleukin Receptor Common gamma Subunit / deficiency
  • Janus Kinase 3 / deficiency
  • Longitudinal Studies
  • Retrospective Studies
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / metabolism
  • Severe Combined Immunodeficiency / pathology
  • Severity of Illness Index
  • T-Lymphocytes*
  • Tetanus Toxoid / therapeutic use
  • Transplantation Chimera
  • Vaccination

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, CD34
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • Glycoproteins
  • Immunoglobulin G
  • Interleukin Receptor Common gamma Subunit
  • Tetanus Toxoid
  • JAK3 protein, human
  • Janus Kinase 3