Lineage-specific chimaerism after stem cell transplantation in children following reduced intensity conditioning: potential predictive value of NK cell chimaerism for late graft rejection.
Chimaerism of FACS-sorted leucocyte subsets (CD14+, CD15+, CD3-/56+, CD3+/4+, CD3+/8+, CD19+) was monitored prospectively between days +14 and +100 in 39 children undergoing allogeneic stem cell transplantation with reduced intensity-conditioning regimens. Cell subsets exceeding 1% of nucleated cells were subject to cell sorting. Chimaerism was analysed by dual-colour FISH and/or by short tandem repeat-polymerase chain reaction. The chimaerism pattern on day +28 was evaluated with regard to its correlation with graft rejection. Of 39 patients, nine patients had donor chimaerism (DC) in all subsets. Mixed/recipient chimaerism (MC/RC) was detectable within T cells in 62%, within NK cells in 39% and within monocytes and granulocytes in 38% of the patients. The correlation of secondary graft rejection with the chimaerism pattern on day +28 revealed the strongest association between RC in NK-cells (P<0.0001), followed by T cells (P=0.001), and granulocytes and monocytes (P=0.034). Notably, patients with RC in T cells rejected their graft only if MC or RC was also present in the NK-cell subset. By contrast, none of the children with DC in NK cells experienced a graft rejection. These observations suggest that, in the presence of recipient T-cell chimaerism, the chimaerism status in NK-cells on day +28 might be able to identify patients at high risk for late graft rejection.
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000145:classification / Q000627:therapeutic use; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D012189:Retrospective Studies; D035781:Siblings; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods
D007166:Immunosuppressive Agents