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Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia.
- Source :
-
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2010 Nov; Vol. 16 (11), pp. 1557-66. Date of Electronic Publication: 2010 Jun 25. - Publication Year :
- 2010
-
Abstract
- To analyze immunohematologic reconstitution, particularly of natural killer (NK) cells, we evaluated 13 β-thalassemia patients after 20 and 60 days and 1 year posttransplantation with T cell-depleted HLA-haploidentical stem cells. We assessed lymphocyte and bone marrow (BM) progenitor cell phenotype and differentiation capacity, spontaneous BM cytokine production, stromal cells, and stromal cell interleukin (IL)-7 production. A reduced clonogenic capability manifested at day +20. Patients had significantly lower CD4(+) T cells versus controls, mainly in the CD45RA(+)CD62L(+) subset. NKs were among the first lymphocytes to repopulate the peripheral blood. At day +60, an increase in primitive BM progenitor cells paralleled small increases in CD4(+), naïve CD4(+), and thymic naïve Th cells. A significant increase in CD4(+) and CD8(+) markers paralleled an increase in CD3⁻CD16(+) NKs, especially with full engraftment. In patients with stable mixed chimerism we observed very low levels of CD3(+) donor chimerism early after transplant that increased over time, but a stable population of high donor NK cells, suggesting a role of these cells on donor engraftment. Stromal cells secreted less IL-7 and displayed "macrophage-like" morphology. Patients initially manifested impaired stem/progenitor cell growth and differentiation capacity in parallel with altered T cell homeostasis and a reduced T cell naïve compartment. We hypothesize that T cell compartment damage partly arises from altered new T cell production from the hematopoietic stem/progenitor cells under stromal cytokine influence. NNK subset analysis might be useful for determining transplant outcome.<br /> (Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- B-Lymphocytes cytology
Blood Cells cytology
Bone Marrow Cells cytology
Bone Marrow Cells metabolism
CD4-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes cytology
Cell Count
Child
Child, Preschool
Chimera blood
Colony-Forming Units Assay
Graft Rejection immunology
Graft Survival immunology
HLA Antigens genetics
HLA Antigens immunology
Humans
Interleukin-2 metabolism
Interleukin-7 metabolism
Killer Cells, Natural cytology
Living Donors
Lymphocyte Count
Mothers
Stromal Cells cytology
Stromal Cells metabolism
T-Lymphocyte Subsets cytology
Transplants
Treatment Outcome
Tumor Necrosis Factor-alpha metabolism
Hematopoietic Stem Cell Transplantation methods
Histocompatibility, Maternal-Fetal
Lymphocyte Depletion
Lymphocytes cytology
T-Lymphocytes cytology
beta-Thalassemia therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1523-6536
- Volume :
- 16
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 20546907
- Full Text :
- https://doi.org/10.1016/j.bbmt.2010.05.003