Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation
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- 作者：Mauro ; Di Ianni Dr.a ; ; b ; ; mauro.diianni@cc.univaq.it ; Franca ; Falzetti Dr.a ; Alessandra ; Carotti Dr.a ; Adelmo ; Terenzi Dr.a ; Beatrice ; Del Papa Dr.a ; Katia ; Perruccio Dr.a ; Loredana ; Ruggeri Dr.a ; Paolo ; Sportoletti Dr.a ; Emanuela ; Rosati Dr.c ; Pierfrancesco ; Marconi Prof.c ; Brunangelo ; Falini Prof.a ; Yair ; Reisner Prof.d ; Andrea ; Velardi Prof.a ; Franco ; Aversa Prof.a ; Massimo F. ; Martelli Prof.a
- 关键词：Treg ; GvHD ; haploidentical transplantation
- 刊名：Best Practice Research Clinical Haematology
- 出版年：2011
- 出版时间：September 2011
- 年：2011
- 卷：24
- 期：3
- 页码：459-466
- 全文大小：463 K
文摘
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?¡Ý?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.