title: Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation.
abstract: The most advanced frontier of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is represented by the use of an HLA-partially matched relative as donor. In this type of transplantation, donor-derived natural killer (NK) cells, which are alloreactive toward recipient cells, significantly contribute to the eradication of leukemia blasts. Alloreactive NK cells may also kill host dendritic cells and T lymphocytes, thus preventing graft-versus-host disease and graft rejection, respectively. Sophisticated strategies of adoptive infusion of T-cell lines/clones specific for the most life-threatening pathogens (namely cytomegalovirus, Epstein-Barr virus, Aspergillus and Adenovirus) have been envisaged, and successfully tested in a few pilot trials, to protect the recipient in the early post-transplantation period. In these patients, also ex-vivo expanded mesenchymal stromal cells have been shown to be beneficial for preventing graft failure. Novel and effective strategies aimed at further augmenting the graft-versus-leukemia effect and at optimizing prevention/treatment of opportunistic/viral infections are warranted.
authors.affiliation: Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Piazza S. Onofrio, Rome, Italy. franco.locatelli@opbg.net
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Luciana
authors.initials: L
authors.lastname: Vinti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palumbo
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.forename: Angela
authors.initials: A
authors.lastname: Mastronuzzi
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Paolo
authors.initials: P
authors.lastname: Dellabona
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgiani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
mesh_terms: D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control