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HLA-haploidentical stem cell transplantation after removal of αβ+ T and B-cells in children with non-malignant disorders

Alice Bertaina, Pietro Merli, Sergio Rutella, Daria Pagliara, Maria Ester Bernardo, Riccardo Masetti, Daniela Pende, Michela Falco, Rupert Handgretinger, Francesca Moretta, Barbarella Lucarelli, Letizia P. Brescia, Giuseppina Li Pira, Manuela Testi, Caterina Cancrini, Nabil Kabbara, Rita Carsetti, Andrea Finocchi, Alessandro Moretta, Lorenzo Moretta and Franco Locatelli

Key points

  • Removal of αβ+ T and CD19+ B cells is an effective strategy for successful HLA-haploidentical hematopoietic stem cell transplantation.

  • The high probability of disease-free survival renders this transplant option attractive for any child with non-malignant disorders.

Abstract

Twenty-three children (15 males, 8 females, median age 3.3 years) with non-malignant 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 16.8x106/kg, 40x103/kg and 40x103/kg, respectively. No patient received any post-transplantation pharmacological graft-versus-host disease (GvHD) prophylaxis. All patients but 4 engrafted, these latter being rescued by a second allograft. Three patients experienced skin-only grade I-II 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 (range 5-40), 21/23 children are alive and disease-free, the 2-year probability of disease-free survival being 91.1%. Recovery of γδ+ T cells was prompt, while αβ+ T cells progressively ensued over time. Our data suggest that this novel graft manipulation strategy is safe and effective for HLA-haplo-HSCT. This study was registered at clinicaltrials.gov, identifier: NCT01810120.

  • Submitted March 21, 2014.
  • Accepted May 16, 2014.