Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia.

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.

• Authors: Antonella Isgrò, Marco Marziali, Pietro Sodani, Javid Gaziev, Buket Erer, Paola Polchi, Katia Paciaroni, Andrea Roveda, Gioia De Angelis, Cristiano Gallucci, Cecilia Alfieri, Maria Domenica Simone, Francesco Zinno, Giancarlo Isacchi, Gaspare Adorno, Alessandro Lanti, Wilma Leti, Fernando Aiuti, Daniela Fraboni, Marco Andreani, Guido Lucarelli
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 16 Issue 11 Pg. 1557-66 (Nov 2010) ISSN: 1523-6536 [Electronic] United States
• PMID: 20546907 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• HLA Antigens
• IL7 protein, human
• Interleukin-2
• Interleukin-7
• Tumor Necrosis Factor-alpha

Topics

• B-Lymphocytes (cytology)
• Blood Cells (cytology)
• Bone Marrow Cells (cytology, 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, immunology)
• Hematopoietic Stem Cell Transplantation (methods)
• Histocompatibility, Maternal-Fetal
• Humans
• Interleukin-2 (metabolism)
• Interleukin-7 (metabolism)
• Killer Cells, Natural (cytology)
• Living Donors
• Lymphocyte Count
• Lymphocyte Depletion
• Lymphocytes (cytology)
• Mothers
• Stromal Cells (cytology, metabolism)
• T-Lymphocyte Subsets (cytology)
• T-Lymphocytes (cytology)
• Transplants
• Treatment Outcome
• Tumor Necrosis Factor-alpha (metabolism)
• beta-Thalassemia (therapy)