INTRODUCTION: 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. PATIENTS AND 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.
INTRODUCTION: 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 donorCD4/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. PATIENTS AND 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: B Del Papa; A Pierini; P Sportoletti; S Baldoni; D Cecchini; E Rosati; E Dorillo; P Aureli; T Zei; R Iacucci Ostini; L Ruggeri; A Carotti; A Velardi; R Negrin; M F Martelli; F Falzetti; M Di Ianni Journal: Leukemia Date: 2016-04-29 Impact factor: 11.528
Authors: Alana A Kennedy-Nasser; Stephanie Ku; Paul Castillo-Caro; Yasmin Hazrat; Meng-Fen Wu; Hao Liu; Jos Melenhorst; A John Barrett; Sawa Ito; Aaron Foster; Barbara Savoldo; Eric Yvon; George Carrum; Carlos A Ramos; Robert A Krance; Kathryn Leung; Helen E Heslop; Malcolm K Brenner; Catherine M Bollard Journal: Clin Cancer Res Date: 2014-02-26 Impact factor: 12.531
Authors: J Pidala; J Kim; M Schell; S J Lee; R Hillgruber; V Nye; E Ayala; M Alsina; B Betts; R Bookout; H F Fernandez; T Field; F L Locke; T Nishihori; J L Ochoa; L Perez; J Perkins; J Shapiro; C Tate; M Tomblyn; C Anasetti Journal: Bone Marrow Transplant Date: 2012-08-06 Impact factor: 5.483