title: Tolerance and chimerism.
abstract: Stem-cell transplantation from human leukocyte antigen (HLA)-haploidentical family members carries a high risk of rejection and graft-versus-host disease (GVHD) if donor and recipient differ by more than one HLA antigen. The authors have developed treatment protocols from studies in dog leukocyte antigen-haploidentical dogs that prevent rejection and modify GVHD to the extent that patients with aggressive hematologic neoplasia can be treated with success. Principal improvements have been achieved in the use of cyclophosphamide and total-body irradiation for conditioning and T-cell depletion for prevention of GVHD. More recently, the combination of marrow and CD6-depleted mobilized donor blood cells (MDBC) has been introduced for HLA-haploidentical transplantation on the basis that CD6-depleted MDBC contain immunoregulatory cells besides stem cells and natural killer cells. Clinical results are reported on 36 patients with high-risk hematologic neoplasia. The results encourage the use of HLA-haploidentical stem-cell transplantation at an earlier stage of the disease. This method could also be of use for tolerance induction in organ transplantation.
authors.affiliation: Clinical Cooperative Group Haematopoietic Cell Transplantation, Department of Medicine III, University of Munich, Grosshadern, Munich, Germany. kolb@med3.med.uni-muenchen.de
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Guenther
authors.forename: Boglarka
authors.initials: B
authors.lastname: Gyurkocza
authors.forename: Florian
authors.initials: F
authors.lastname: Hoetzl
authors.forename: Belinda
authors.initials: B
authors.lastname: Simoes
authors.forename: Christine
authors.initials: C
authors.lastname: Falk
authors.forename: Michael
authors.initials: M
authors.lastname: Schleuning
authors.forename: Georg
authors.initials: G
authors.lastname: Ledderose
mesh_terms: D000818:Animals; D001787:Blood Group Incompatibility; D003520:Cyclophosphamide / Q000494:pharmacology; D004285:Dogs; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007938:Leukemia / Q000601:surgery; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance; D014916:Whole-Body Irradiation
chemical_list: D003520:Cyclophosphamide