Post-transplant cyclophosphamide (pt-Cy) is highly effective in preventing graft-versus-host disease in patients with blood cancers treated with T-replete haploidentical transplantation. In collaboration with the Transplantation Program at the Humanitas Cancer Center (Dr. Luca Castagna) and the Unit of Clinical and Experimental Immunology (Dr. Domenico Mavilio), we recently unravelled the cellular mechanisms at the basis of pt-Cy and leading to successful immune reconstitution (Figure 2; http://www.bloodjournal.org/content/early/2015/03/05/blood-2014-11-608406). The group recently demonstrated that T memory stem cells (TSCM), a subset of T cells capable to simultaneously self-renew and generate more differentiated progeny, play a fundamental role in the recovery of pathogen and tumor-specific T cells in patients with blood cancer receiving bone marrow transplantation from haploidentical donors (Roberto A. et al., Blood, 2015). We are currently investigating the durability of donor T cell responses transferred with the graft along with their protective capacity.

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Figure 2. Cellular mechanisms of T cell reconstitution following T-replete haploidentical bone marrow transplantation and post-transplant cyclophosphamide

This research was originally published in Blood. Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, Gandolfi S, Tentorio P, Sarina B, Timofeeva I, Santoro A, Carlo-Stella C, Bruno B, Carniti C, Corradini P, Gostick E, Ladell K, Price DA, Roederer M, Mavilio D, Lugli E. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood. 2015;125:2855-64. © by the American Society of Hematology