title: HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders.
abstract: Twenty-three children with nonmalignant disorders received HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) after ex vivo elimination of αβ(+) T cells and CD19(+) B cells. The median number of CD34(+), αβ(+)CD3(+), and B cells infused was 16.8 × 10(6), 40 × 10(3), and 40 × 10(3) cells/kg, respectively. No patient received any posttransplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD). All but 4 patients engrafted, these latter being rescued by a second allograft. Three patients experienced skin-only grade 1 to 2 acute GVHD. No patient developed visceral acute or chronic GVHD. Cumulative incidence of transplantation-related mortality was 9.3%. With a median follow-up of 18 months, 21 of 23 children are alive and disease-free, the 2-year probability of disease-free survival being 91.1%. Recovery of γδ(+) T cells was prompt, but αβ(+) T cells progressively ensued over time. Our data suggest that this novel graft manipulation strategy is safe and effective for haplo-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy; Department of Medical Sciences, Catholic University Medical School, Rome, Italy;
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Daria
authors.initials: D
authors.lastname: Pagliara
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.affiliation: Department of Pediatrics, Sant'Orsola Hospital, University of Bologna, Bologna, Italy;
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy;
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini, Genoa, Italy;
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany;
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Moretta
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Barbarella
authors.initials: B
authors.lastname: Lucarelli
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Letizia P
authors.initials: LP
authors.lastname: Brescia
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Li Pira
authors.affiliation: Laboratory of Immunogenetics and Transplant Biology, Istituto Mediterraneo di Ematologia Foundation at Tor Vergata University Hospital, Rome, Italy;
authors.forename: Manuela
authors.initials: M
authors.lastname: Testi
authors.affiliation: University Department of Pediatrics, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, University of Rome Tor Vergata, Rome, Italy;
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.affiliation: Pediatric Hematology Oncology Division, Rafic Hariri University Hospital, Beirut, Lebanon;
authors.forename: Nabil
authors.initials: N
authors.lastname: Kabbara
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
authors.affiliation: University Department of Pediatrics, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, University of Rome Tor Vergata, Rome, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Genoa, Italy; and.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini, Genoa, Italy;
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy; Department of Pediatrics, University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D064591:Allografts; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012189:Retrospective Studies; D013601:T-Lymphocytes
chemical_list: D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta