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Touzot, Fabien, MD, PhD; Neven, Bénédicte, MD, PhD; Dal-Cortivo, Liliane, MD; Gabrion, Aurélie, MSc; Moshous, Despina, MD, PhD; Cros, Guilhem, MD; Chomton, Maryline, MD; Luby, Jean-Marc, PGDipMLSc; Terniaux, Brigitte, PGDipMLSc; Magalon, Jérémy, PharmD, MSc; Picard, Capucine, MD, PhD; Blanche, Stéphane, MD; Fischer, Alain, MD, PhD; Cavazzana, Marina, MD, PhD
Journal of allergy and clinical immunology, 05/2015, Volume: 135, Issue: 5Journal Article
Background Combined immunodeficiencies (CIDs) form a heterogeneous group of inherited conditions that affect the development, function, or both of T cells. The treatment of CIDs with allogeneic hematopoietic stem cell transplantation (HSCT) is complicated by a high incidence of life-threatening infections and an increased risk of graft-versus-host disease (GVHD). Objective In view of the growing evidence that alloreactivity is mainly derived from human naive T cells, the selective depletion of naive T cells from allografts might constitute a way of reducing alloreactivity while maintaining memory T-cell responsiveness to pathogens. Methods Five consecutive patients with CIDs and chronic viral infections underwent an allogeneic, HLA-mismatched HSCT. Given the patients' infection status and the potential risk of severe GVHD in the mismatched setting, the CD34− fraction of the allograft was depleted of naive T cells by using magnetic CD45RA beads. Results Engraftment occurred in 4 of the 5 patients. No severe GVHD occurred. In the 4 engrafted patients viral infections were cleared within 2 months of the HSCT, and both cellular and humoral immunity were re-established within a year of the HSCT. An early T-cell response against viral pathogens was documented in 2 patients. Conclusion The present pilot study shows that clinical-grade depletion of naive T cells from an allograft through the use of magnetic CD45RA beads seems to be a feasible and efficacious option for the treatment of patients with CIDs at high risk of GVHD, infection, or both in an HLA-mismatched setting.
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