Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation

• Published in: Best practice & research. Clinical haematology Vol. 24; no. 3; pp. 459 - 466
• Main Authors: Di Ianni, Mauro, Dr, Falzetti, Franca, Dr, Carotti, Alessandra, Dr, Terenzi, Adelmo, Dr, Del Papa, Beatrice, Dr, Perruccio, Katia, Dr, Ruggeri, Loredana, Dr, Sportoletti, Paolo, Dr, Rosati, Emanuela, Dr, Marconi, Pierfrancesco, Prof, Falini, Brunangelo, Prof, Reisner, Yair, Prof, Velardi, Andrea, Prof, Aversa, Franco, Prof, Martelli, Massimo F., Prof
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2011
• Subjects: Adult; Antigens, CD34; CD4 Lymphocyte Count; Female; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; GvHD; haploidentical transplantation; Hematology, Oncology and Palliative Medicine; Histocompatibility Testing; Humans; Immunotherapy, Adoptive; Leukemia - blood; Leukemia - immunology; Leukemia - therapy; Lymphocyte Depletion; Lymphoma, Non-Hodgkin - blood; Lymphoma, Non-Hodgkin - immunology; Lymphoma, Non-Hodgkin - therapy; Male; Middle Aged; Stem Cell Transplantation; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - transplantation; Tissue Donors; Transplantation, Homologous; Treg; haploidentical transplantation; GvHD; Treg
• ISSN: 1521-6926; 1532-1924
• DOI: 10.1016/j.beha.2011.05.005

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.