title: Selective Depletion of αβ T Cells and B Cells for Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation. A Three-Year Follow-Up of Procedure Efficiency.
abstract: HLA-haploidentical family donors represent a valuable option for children requiring allogeneic hematopoietic stem cell transplantation (HSCT). Because graft-versus-host diseases (GVHD) is a major complication of HLA-haploidentical HSCT because of alloreactive T cells in the graft, different methods have been used for ex vivo T cell depletion. Removal of donor αβ T cells, the subset responsible for GVHD, and of B cells, responsible for post-transplantation lymphoproliferative disorders, have been recently developed for HLA-haploidentical HSCT. This manipulation preserves, in addition to CD34+progenitors, natural killer, γδ T, and monocytes/dendritic cells, contributing to anti-leukemia activity and protection against infections. We analyzed depletion efficiency and cell yield in 200 procedures performed in the last 3 years at our center. Donors underwent CD34+hematopoietic stem cell (HSC) peripheral blood mobilization with granulocyte colony-stimulating factor (G-CSF). Poor CD34+cell mobilizers (48 of 189, 25%) received plerixafor in addition to G-CSF. Aphereses containing a median of 52.5 × 109nucleated cells and 494 × 106CD34+HSC were manipulated using the CliniMACS device. In comparison to the initial product, αβ T cell depletion produced a median 4.1-log reduction (range, 3.1 to 5.5) and B cell depletion led to a median 3.4-log reduction (range, 2.0 to 4.7). Graft products contained a median of 18.5 × 106CD34+HSC/kg recipient body weight, with median values of residual αβ T cells and B cells of 29 × 103/kg and 33 × 103/kg, respectively. Depletion efficiency monitored at 6-month intervals demonstrated steady performance, while improved recovery of CD34+cells was observed after the first year (P = .0005). These data indicate that αβ T cell and B cell depletion of HSC grafts from HLA-haploidentical donors was efficient and reproducible.
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. Electronic address: giuseppina.lipira@opbg.net.
authors: Giuseppina
authors: G
authors: Li Pira
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: David
authors: D
authors: Malaspina
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Elia
authors: E
authors: Girolami
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Simone
authors: S
authors: Biagini
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Elisabetta
authors: E
authors: Cicchetti
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Gianpiero
authors: G
authors: Conflitti
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Manuel
authors: M
authors: Broglia
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Stefano
authors: S
authors: Ceccarelli
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Stefania
authors: S
authors: Lazzaro
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Daria
authors: D
authors: Pagliara
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Antonella
authors: A
authors: Meschini
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Alice
authors: A
authors: Bertaina
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors: Mauro
authors: M
authors: Montanari
authors: Department of Pediatric Hematology-Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy; Department of Pediatric Sciences, University of Pavia, Pavia, Italy.
authors: Franco
authors: F
authors: Locatelli
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology; D000075442:Transplantation, Haploidentical / Q000379:methods*
chemical_list: D018952:Antigens, CD34; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Graft manipulation; HLA-haploidentical transplantation; αβ T cell depletion