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.

Isgrò, A., Marziali, M., Sodani, P., Gaziev, J., Erer, B., Polchi, P., et al. (2010). Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 16(11), 1557-1566 [10.1016/j.bbmt.2010.05.003].

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

De Angelis, G;Zinno, F;Isacchi, G;Adorno, G;Lucarelli, G
2010-11-01

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.
nov-2010
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/05 - PATOLOGIA CLINICA
English
Con Impact Factor ISI
Humans; Child; Lymphocytes; B-Lymphocytes; Transplants; Blood Cells; Lymphocyte Count; Graft Rejection; Chimera; Killer Cells, Natural; Treatment Outcome; Hematopoietic Stem Cell Transplantation; T-Lymphocytes; Tumor Necrosis Factor-alpha; Cell Count; Mothers; Stromal Cells; CD4-Positive T-Lymphocytes; Child, Preschool; Living Donors; beta-Thalassemia; Bone Marrow Cells; HLA Antigens; Interleukin-2; CD8-Positive T-Lymphocytes; Graft Survival; Lymphocyte Depletion; Interleukin-7; Histocompatibility, Maternal-Fetal; Colony-Forming Units Assay; T-Lymphocyte Subsets
Isgrò, A., Marziali, M., Sodani, P., Gaziev, J., Erer, B., Polchi, P., et al. (2010). Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 16(11), 1557-1566 [10.1016/j.bbmt.2010.05.003].
Isgrò, A; Marziali, M; Sodani, P; Gaziev, J; Erer, B; Polchi, P; Paciaroni, K; Roveda, A; De Angelis, G; Gallucci, C; Alfieri, C; Simone, M; Zinno, F...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/56210
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