International Journal of Hematology

, Volume 106, Issue 6, pp 860–864 | Cite as

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

  • 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
Case Report

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.

Keywords

Tregs DLI GvHD/GvL 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12185_2017_2292_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 kb)

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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Mauro Di Ianni
    • 1
    • 2
  • Paola Olioso
    • 1
  • Raffaella Giancola
    • 1
  • Stella Santarone
    • 1
  • Annalisa Natale
    • 1
  • Gabriele Papalinetti
    • 1
  • Ida Villanova
    • 1
  • Stefano Baldoni
    • 2
  • Ambra Di Tommaso
    • 2
  • Tiziana Bonfini
    • 1
  • Patrizia Accorsi
    • 1
  • Paolo Di Bartolomeo
    • 1
  1. 1.Department of HematologyTransfusion Medicine and Biotechnologies, Ospedale CivilePescaraItaly
  2. 2.Hematology Section, Department of Life, Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

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