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

• Published in: International journal of hematology 2017-12, Vol.106 (6), p.860-864
• Main Authors: Di Ianni, Mauro, Olioso, Paola, Giancola, Raffaella, Santarone, Stella, Natale, Annalisa, Papalinetti, Gabriele, Villanova, Ida, Baldoni, Stefano, Di Tommaso, Ambra, Bonfini, Tiziana, Accorsi, Patrizia, Di Bartolomeo, Paolo
• Format: Article
• Language: English
• Subjects: Adoptive immunotherapy; Allografts; Bone marrow; Bone marrow transplantation; Case Report; Chimerism; Cytometry; Graft versus host disease; Graft vs Leukemia Effect - immunology; Graft-versus-host reaction; Graft-versus-leukemia reaction; Grafting; Hematology; Hematopoietic Stem Cell Transplantation; Humans; Immunology; Immunoregulation; Immunotherapy; Leukemia; Leukemia, Promyelocytic, Acute - immunology; Leukemia, Promyelocytic, Acute - pathology; Leukemia, Promyelocytic, Acute - therapy; Lymphocyte Transfusion; Lymphocytes T; Male; Medicine; Medicine & Public Health; Notch1 protein; Oncology; Patients; Peripheral blood; Stem cell transplantation; T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - transplantation; Tissue Donors; Transplantation; Transplants & implants
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-017-2292-3

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 × 10 6 /kg Tregs derived from matched donor followed 7 days later by 5 × 10 6 /kg Tcons. GvL effect was strongly evident as the percentage of leukemic cells decreased to 5%. A second infusion of Tregs (2.5 × 10 6 /kg) and Tcons (2 × 10 6 /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.