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

被引:41
作者
Slatter, Mary A. [1 ]
Brigham, Kenneth [2 ]
Dickinson, Anne M. [2 ]
Harvey, Helen L. [1 ]
Barge, Dawn [3 ]
Jackson, Antony
Bown, Nicholas
Flood, Terence J. [1 ]
Cant, Andrew J. [1 ,4 ]
Abinun, Mario [1 ,4 ]
Gennery, Andrew R. [1 ,4 ]
机构
[1] Newcastle Upon Tyne Hosp Fdn Trust, Dept Paediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England
[2] Newcastle Upon Tyne Hosp Fdn Trust, Stem Cell Lab, Newcastle Upon Tyne, Tyne & Wear, England
[3] Newcastle Upon Tyne Hosp Fdn Trust, Reg Immunol Lab, Newcastle Upon Tyne, Tyne & Wear, England
[4] Univ Newcastle Upon Tyne, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
关键词
severe combined immunodeficiency; hematopoietic stem cell transplantation; T-cell depletion; CD34(+) stem cell selection; immune reconstitution;
D O I
10.1016/j.jaci.2007.10.035
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 X(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.
引用
收藏
页码:361 / 367
页数:7
相关论文
共 27 条
[1]   Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies:: report of the European experience 1968-99 [J].
Antoine, C ;
Müller, S ;
Cant, A ;
Cavazzana-Calvo, M ;
Veys, P ;
Vossen, J ;
Fasth, A ;
Heilmann, C ;
Wulffraat, N ;
Seger, R ;
Blanche, S ;
Friedrich, W ;
Abinun, M ;
Davies, G ;
Bredius, R ;
Schulz, A ;
Landais, P ;
Fischer, A .
LANCET, 2003, 361 (9357) :553-560
[2]   Regulatory T cells control autoimmunity following syngeneic bone marrow transplantation [J].
Benard, Angele ;
Ceredig, Rhodri ;
Rolink, Antonius G. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (09) :2324-2335
[3]   Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry [J].
Berrington, JE ;
Barge, D ;
Fenton, AC ;
Cant, AJ ;
Spickett, GP .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2005, 140 (02) :289-292
[4]   Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency [J].
Borghans, Jose A. ;
Bredius, Robbert G. ;
Hazenberg, Mette D. ;
Roelofs, Helene ;
Zijde, Els C. Jol-van der ;
Heidt, Jeroen ;
Otto, Sigrid A. ;
Kuijpers, Taco W. ;
Fibbe, Willem E. ;
Vossen, Jaak M. ;
Miedema, Frank ;
van Tol, Maarten J. .
BLOOD, 2006, 108 (02) :763-769
[5]   Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency [J].
Buckley, RH ;
Schiff, SE ;
Schiff, RI ;
Markert, ML ;
Williams, LW ;
Roberts, JL ;
Myers, LA ;
Ward, FE .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (07) :508-516
[6]   Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype [J].
Cavazzana-Calvo, Marina ;
Carlier, Frederique ;
Le Deist, Francoise ;
Morillon, Estelle ;
Taupin, Pierre ;
Gautier, David ;
Radford-Weiss, Isabelle ;
Caillat-Zucman, Sophie ;
Neven, Benedicte ;
Blanche, Stephane ;
Cheynier, Remi ;
Fischer, Alain ;
Hacein-Bey-Abina, Salima .
BLOOD, 2007, 109 (10) :4575-4581
[7]   Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency [J].
Chinen, Javier ;
Davis, Joie ;
De Ravin, Suk See ;
Hay, Beverly N. ;
Hsu, Amy P. ;
Linton, Gilda F. ;
Naumann, Nora ;
Nomicos, Effie Y. H. ;
Silvin, Christopher ;
Ulrick, Jean ;
Whiting-Theobald, Narda L. ;
Malech, Harry L. ;
Puck, Jennifer M. .
BLOOD, 2007, 110 (01) :67-73
[8]   Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion [J].
Devine, SM ;
Bartholomew, AM ;
Mahmud, N ;
Nelson, M ;
Patil, S ;
Hardy, W ;
Sturgeon, C ;
Hewett, T ;
Chung, T ;
Stock, W ;
Sher, D ;
Weissman, S ;
Ferrer, K ;
Mosca, J ;
Deans, R ;
Moseley, A ;
Hoffman, R .
EXPERIMENTAL HEMATOLOGY, 2001, 29 (02) :244-255
[9]   In vitro T cell depletion using Campath 1M for mismatched BMT for severe combined immunodeficiency (SCID) [J].
Dickinson, AM ;
Reid, MM ;
Abinun, M ;
Peak, J ;
Brigham, K ;
Dunn, J ;
Cant, AJ .
BONE MARROW TRANSPLANTATION, 1997, 19 (04) :323-329
[10]   Severe combined immunodeficiency.: A model disease for molecular immunology and therapy [J].
Fischer, A ;
Le Deist, F ;
Hacein-Bey-Abina, S ;
André-Schmutz, I ;
Basile, GD ;
de Villartay, JP ;
Cavazzana-Calvo, M .
IMMUNOLOGICAL REVIEWS, 2005, 203 :98-109