Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia.
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
Antonella
A
International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy. a.isgro@fondazioneime.org
Marziali
Marco
M
Sodani
Pietro
P
Gaziev
Javid
J
Erer
Buket
B
Polchi
Paola
P
Paciaroni
Katia
K
Roveda
Andrea
A
De Angelis
Gioia
G
Gallucci
Cristiano
C
Alfieri
Cecilia
C
Simone
Maria Domenica
MD
Zinno
Francesco
F
Isacchi
Giancarlo
G
Adorno
Gaspare
G
Lanti
Alessandro
A
Leti
Wilma
W
Aiuti
Fernando
F
Fraboni
Daniela
D
Andreani
Marco
M
Lucarelli
Guido
G
D001402:B-Lymphocytes / Q000166:cytology; D001773:Blood Cells / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D002678:Chimera / Q000097:blood; D003114:Colony-Forming Units Assay; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D054502:Histocompatibility, Maternal-Fetal; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology; D019520:Living Donors; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000166:cytology*; D009035:Mothers; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D019737:Transplants; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017086:beta-Thalassemia / Q000628:therapy*
D006680:HLA Antigens; C508605:IL7 protein, human; D007376:Interleukin-2; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha