title: Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants.
abstract: Sixteen patients conditioned with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA-matched donors in a tolerance induction protocol. Blood cell monitoring included changes in chimerism, balance of T-cell subsets and responses to donor alloantigens. Fifteen patients developed multilineage chimerism without graft-versus-host disease (GVHD), and eight with chimerism for at least 6 months were withdrawn from antirejection medications for 1-3 years (mean, 28 months) without subsequent rejection episodes. Four chimeric patients have just completed or are in the midst of drug withdrawal, and four patients were not withdrawn due to return of underlying disease or rejection episodes. Blood cells from all patients showed early high ratios of CD4+CD25+ regulatory T cells and NKT cells versus conventional naive CD4+ T cells, and those off drugs showed specific unresponsiveness to donor alloantigens. In conclusion, TLI and ATG promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and hematopoietic donor cell infusions. All 16 patients had excellent graft function at the last observation point with or without maintenance drugs.
authors.affiliation: Department of Medicine (Nephrology), Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Scandling
authors.forename: S
authors.initials: S
authors.lastname: Busque
authors.forename: S
authors.initials: S
authors.lastname: Dejbakhsh-Jones
authors.forename: C
authors.initials: C
authors.lastname: Benike
authors.forename: M
authors.initials: M
authors.lastname: Sarwal
authors.forename: M T
authors.initials: MT
authors.lastname: Millan
authors.forename: J A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: R
authors.initials: R
authors.lastname: Lowsky
authors.forename: E G
authors.initials: EG
authors.lastname: Engleman
authors.forename: S
authors.initials: S
authors.lastname: Strober
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001787:Blood Group Incompatibility; D005260:Female; D005455:Fluorescent Antibody Technique; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D018183:Transplantation Chimera; D014181:Transplantation Immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents