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

Giuseppina Li Pira, David Malaspina, Elia Girolami, Simone Biagini, Elisabetta Cicchetti, Gianpiero Conflitti, Manuel Broglia, Stefano Ceccarelli, Stefania Lazzaro, Daria Pagliara, Antonella Meschini, Alice Bertaina, Mauro Montanari, Franco Locatelli

Research output: Contribution to journalArticle

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 × 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.

Original languageEnglish
Pages (from-to)2056-2064
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • Graft manipulation
  • HLA-haploidentical transplantation
  • αβ T cell depletion

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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