title: Chimerism studies in HLA-identical nonmyeloablative hematopoietic stem cell transplantation point to the donor CD8(+) T-cell count on day + 14 as a predictor of acute graft-versus-host disease.
abstract: Chimerism analysis of hematopoietic cells has emerged as an essential tool in nonmyeloablative hematopoietic stem cell transplantation. We have investigated the development of donor chimerism in granulocytes and CD4(+) and CD8(+) T cells in blood and bone marrow of 24 patients with hematologic malignancies who received HLA-identical sibling peripheral blood stem cell grafts after conditioning with fludarabine and 2 Gy of total body irradiation. The T-cell chimerism of blood and bone marrow was tightly correlated. Complete donor chimerism was reached earlier in the granulocytes than in the T cells. Mixed T-cell chimerism was common at the time of onset of acute graft-versus-host disease (aGVHD), and both CD4(+) and CD8(+) donor T-cell chimerism increased with the occurrence of aGVHD grades II to IV (P =.0002 and P =.019, respectively). The rate of disappearance of recipient CD8(+) T cells was faster in patients with aGVHD grades II to IV than in patients without clinically significant aGVHD (P =.016). This observation indicates a role of graft-versus-lymphohematopoietic tissue reactions in creating complete donor T-cell chimerism. A donor CD8(+) T-cell count above the median on day +14 increased the risk of subsequent development of aGVHD grades II to IV (P =.003).
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark. slykkep@rh.dk
authors.forename: Søren L
authors.initials: SL
authors.lastname: Petersen
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.forename: A
authors.initials: A
authors.lastname: Svejgaard
authors.forename: Tania N
authors.initials: TN
authors.lastname: Masmas
authors.forename: Ebbe
authors.initials: E
authors.lastname: Dickmeiss
authors.forename: Carsten
authors.initials: C
authors.lastname: Heilmann
authors.forename: Lars L
authors.initials: LL
authors.lastname: Vindeløv
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000276:immunology; D006087:Graft vs Host Reaction / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007958:Leukocyte Count; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D007166:Immunosuppressive Agents