title: Clinical tolerance after allogeneic hematopoietic stem cell transplantation: a study of influencing factors.
abstract: BACKGROUND
  Clinical tolerance, defined as discontinuation of immunosuppression without immunological events, is often achieved after allogeneic hematopoietic stem cell transplantation, unlike after organ transplantation. However, this phenomenon has rarely been studied.
  
  
  METHODS
  Between September 1977 and December 1997, we evaluated 354 allogeneic hematopoietic stem cell recipients who had had more than 1 year of relapse-free survival, regarding time to discontinuation of immunosuppression. Factors such as patient age, donor age, donor sex, immunosuppressive protocols, cell dose, and graft-versus-host-disease (GVHD) were studied.
  
  
  RESULTS
  Patients who did not develop GVHD had discontinued immunosuppression according to the protocols, within 1 year for malignant diseases and within 2 years for nonmalignant diseases. Patients given methotrexate as a single drug were off immunosuppression faster than those given cyclosporine alone (P=0.05). Children (<18 years) discontinued immunosuppression faster than adults (P=0.05). Low donor age was of greater importance than low recipient age for early discontinuation (P=0.003). Male recipients of stem cells from immunized female donors needed a longer time to discontinuation (P<0.001). Patients without acute GVHD had a shorter time to discontinuation than patients with any grade of GVHD (P=0.02). Thirteen months after hematopoietic stem cell transplantation, 54% of HLA-identical sibling marrow recipients and 36% of unrelated marrow recipients with malignant disease had discontinued immunosuppression (P=0.002). Twenty-five months after hematopoietic stem cell transplantation, the corresponding figures were 69% and 75% in the two groups, respectively.
  
  
  CONCLUSIONS
  In multivariate analysis, high donor age, immunized female donor to male recipient, and grades II-IV acute GVHD were significantly associated with a longer time to clinical tolerance.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden. Patrik.Hentschke@ transpl.hs.sll.se
authors.forename: Patrik
authors.initials: P
authors.lastname: Hentschke
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Barkholt
authors.forename: Johan
authors.initials: J
authors.lastname: Aschan
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D009679:Nuclear Family; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents; D008727:Methotrexate