BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.
BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.
Authors: Asad Bashey; Kouros Owzar; Jeffrey L Johnson; Peggy S Edwards; Michael Kelly; Lee-Ann Baxter-Lowe; Steven Devine; Sherif Farag; David Hurd; Edward Ball; Philip McCarthy; John Lister; Thomas C Shea; Charles Linker Journal: Biol Blood Marrow Transplant Date: 2010-07-30 Impact factor: 5.742
Authors: N S Majhail; C G Brunstein; R Shanley; K Sandhu; B McClune; B Oran; E D Warlick; J E Wagner; D J Weisdorf Journal: Bone Marrow Transplant Date: 2011-05-23 Impact factor: 5.483
Authors: Navneet S Majhail; Claudio G Brunstein; Marcie Tomblyn; Avis J Thomas; Jeffrey S Miller; Mukta Arora; Dan S Kaufman; Linda J Burns; Arne Slungaard; Philip B McGlave; John E Wagner; Daniel J Weisdorf Journal: Biol Blood Marrow Transplant Date: 2008-03 Impact factor: 5.742
Authors: Mark Bosch; Manveer Dhadda; Mette Hoegh-Petersen; Yiping Liu; Laura M Hagel; Peter Podgorny; Alejandra Ugarte-Torres; Faisal M Khan; Joanne Luider; Iwona Auer-Grzesiak; Adnan Mansoor; James A Russell; Andrew Daly; Douglas A Stewart; David Maloney; Michael Boeckh; Jan Storek Journal: Cytotherapy Date: 2012-09-18 Impact factor: 5.414