title: Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation.
abstract: BACKGROUND
  Haploidentical transplantation, with extensive T cell depletion to prevent GvHD, is associated with a high incidence of infection-related deaths. The key challenge is to improve immune recovery with allogeneic donor T cells without triggering GvHD. As T regulatory cells (Tregs) controlled GvHD in pre-clinical studies, the present study evaluated the impact of an infusion of donor CD4/CD25 + Tregs, followed by an inoculum of donor mature T cells (Tcons) and positively immunoselected CD34 + cells in the setting of haploidentical stem cell transplantation.
  
  
  METHODS
  Twenty-eight patients were enrolled in this study (22 AML; 5 ALL; 1 NHL). All received immunoselected Tregs (CliniMACS, Miltenyi Biotec) followed by positively immunoselected CD34 + cells together with Tcons 4 days later. No GvHD prophylaxis was administered.
  
  
  RESULTS
  26/28 patients engrafted. No acute GvHD developed in 24/26 patients; 2 developed ≥ grade II acute GvHD. No patient has developed chronic GvHD. CD4 and CD8 counts rapidly increased after transplant. Episodes of CMV reactivation were significantly fewer than in controls.
  
  
  CONCLUSIONS
  In the setting of haploidentical transplantation infusion of Tregs makes administration of a high dose of T cells feasible. This strategy provides a long-term protection from GvHD and robust immune reconstitution.
authors.affiliation: Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy. mauro.diianni@cc.univaq.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Ianni
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carotti
authors.forename: Adelmo
authors.initials: A
authors.lastname: Terenzi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Del Papa
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Paolo
authors.initials: P
authors.lastname: Sportoletti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rosati
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Marconi
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D018791:CD4 Lymphocyte Count; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000097:blood / Q000276:immunology / Q000628:therapy; D008212:Lymphocyte Depletion; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34