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


CONCLUSIONS
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.
Slatter
Mary A
MA
Department of Paediatric Immunology, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle upon Tyne, United Kingdom.
Brigham
Kenneth
K
Dickinson
Anne M
AM
Harvey
Helen L
HL
Barge
Dawn
D
Jackson
Antony
A
Bown
Nicholas
N
Flood
Terence J
TJ
Cant
Andrew J
AJ
Abinun
Mario
M
Gennery
Andrew R
AR
D000906:Antibodies / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes; D000074301:CD52 Antigen; D006023:Glycoproteins / Q000276:immunology*; D006192:Haemophilus Infections / Q000517:prevention & control; D019741:Haemophilus influenzae type b; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology / Q000628:therapy*; D007156:Immunologic Memory; D007223:Infant; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency; D053616:Janus Kinase 3 / Q000172:deficiency; D008137:Longitudinal Studies; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013601:T-Lymphocytes; D013745:Tetanus Toxoid / Q000627:therapeutic use; D018183:Transplantation Chimera; D014611:Vaccination
D000906:Antibodies; D015703:Antigens, CD; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007074:Immunoglobulin G; D053631:Interleukin Receptor Common gamma Subunit; D013745:Tetanus Toxoid; C507933:JAK3 protein, human; D053616:Janus Kinase 3