International Journal of Hematology

DOI: 10.1007/s12185-017-2292-3 Pages: 860-864

Treg-protected donor lymphocyte infusions: a new tool to address the graft-versus-leukemia effect in the absence of graft-versus-host disease in patients relapsed after HSCT

1. Transfusion Medicine and Biotechnologies, Ospedale Civile, Department of Hematology

2. University of L’Aquila, Hematology Section, Department of Life, Health and Environmental Sciences

Correspondence to:
Mauro Di Ianni
Email: mauro.diianni@cc.univaq.it

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Abstract

In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow). The patient received a first infusion of 2.5 × 106/kg Tregs derived from matched donor followed 7 days later by 5 × 106/kg Tcons. GvL effect was strongly evident as the percentage of leukemic cells decreased to 5%. A second infusion of Tregs (2.5 × 106/kg) and Tcons (2 × 106/kg) was performed. No GvHD was observed. Disease evaluation showed the absence of blastic cells at flow-cytometry, a normal caryotype and full donor chimerism. We also observed NOTCH1 down-regulation in peripheral blood. This new immunotherapy approach showed that Treg-protected DLI is effective in preventing GvHD and is associated with a strong GvL effect.

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