Title |
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
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Published in |
International Journal of Hematology, July 2017
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DOI | 10.1007/s12185-017-2292-3 |
Pubmed ID | |
Authors |
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo |
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 × 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. |
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Unknown | 5 | 33% |