title: Early evaluation of immune reconstitution following allogeneic CD3/CD19-depleted grafts from alternative donors in childhood acute leukemia.
abstract: Graft engineering procedures for hematopoietic SCT (HSCT) may improve the chance of success in matched unrelated donor (MUD) and haploidentical donor transplantations. Successful donor immune reconstitution is important to mediate GVL effects in reduced-intensity conditioning (RIC) HSCT. We prospectively investigated early immune reconstitution and clinical outcome in 30 CD3/CD19-depleted MUD (n=15) or HP (n=15) HSCTs for high-risk childhood leukemia using a fludarabine-based RIC without serotherapy. The graft consisted of a mean of 10.5 × 10(6)/kg CD34+, 77 × 10(3)/kg CD3+ and 39 × 10(6)/kg CD56+ cells. After transplantation, 86% of the patients engrafted. In all, 13% of patients had >grade 3 acute GVHD. Natural killer (NK) cell, DC and T-cell recovery achieved normal values within the first 60 days after transplantation. DC recovery was dominated by the DC2(-) subset. NK-cell phenotype was altered and cytotoxicity was lower compared with their donors. EFS was 50±9% (73±11% for those in CR1 and 26±11% for those with advanced disease). Faster DC2(-) recovery was associated with better outcome, especially in the MUD setting. In summary, CD3/CD19-depleted HSCT with fludarabine-based RIC without serotherapy resulted in favorable patient survival, and rapid NK, DC and T-cell recovery.
authors.affiliation: Department of Hemato-Oncology and Stem Cell Transplantation, Servicio de Hemato-Oncología y Trasplante Hematopoyético, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. aperezm.hnjs@salud.madrid.org
authors.forename: A
authors.initials: A
authors.lastname: Pérez-Martínez
authors.forename: M
authors.initials: M
authors.lastname: González-Vicent
authors.forename: J
authors.initials: J
authors.lastname: Valentín
authors.forename: E
authors.initials: E
authors.lastname: Aleo
authors.forename: A
authors.initials: A
authors.lastname: Lassaletta
authors.forename: J
authors.initials: J
authors.lastname: Sevilla
authors.forename: J L
authors.initials: JL
authors.lastname: Vicario
authors.forename: M
authors.initials: M
authors.lastname: Ramírez
authors.forename: M A
authors.initials: MA
authors.lastname: Díaz
mesh_terms: D000208:Acute Disease; D018941:Antigens, CD19 / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002648:Child; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000276:immunology* / Q000601:surgery*; D008297:Male; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014181:Transplantation Immunology / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; D017252:CD3 Complex