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
| Autor: | Mauro Montanari, David Malaspina, Simone Biagini, Alice Bertaina, Manuel Broglia, Antonella Meschini, Franco Locatelli, Daria Pagliara, Elia Girolami, Giuseppina Li Pira, Stefano Ceccarelli, Elisabetta Cicchetti, Stefania Lazzaro, Gianpiero Conflitti |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Receptors Antigen T-Cell alpha-beta T-Lymphocytes T cell medicine.medical_treatment HLA-haploidentical transplantation CD34 Graft vs Host Disease Lymphoproliferative disorders Antigens CD34 Hematopoietic stem cell transplantation Human leukocyte antigen Lymphocyte Depletion 03 medical and health sciences HLA Antigens Humans Medicine B-Lymphocytes Transplantation business.industry Plerixafor Graft manipulation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell Hematology medicine.disease 030104 developmental biology medicine.anatomical_structure Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA Transplantation Haploidentical Immunology Cancer research graft manipulation αβ T cell depletion Female business Ex vivo Follow-Up Studies medicine.drug |
| Popis: | 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 × 109 nucleated cells and 494 × 106 CD34+ 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 × 106 CD34+ 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. |
| Databáze: | OpenAIRE |
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