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
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.
KeywordsTregs DLI GvHD/GvL
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Schmid C, Labopin M, Nagler A, Bornhäuser M, Finke J, Fassas A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factor analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007;25:4938–45.CrossRefPubMedGoogle Scholar
- 6.Nguyen VH, Zeiser R, Dasilva DL, Chang DS, Beilhack A, Contag CH, et al. In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic stem call transplantation. Blood. 2007;109(6):2649–56.CrossRefPubMedGoogle Scholar
- 14.Orsini E, Alyea EP, Schlossman R, Canning C, Soiffer RJ, Chillemi A, et al. Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host in patients with relapsed multiple myeloma after donor lymphocyte infusion. Bone Marrow Transplant. 2000;25:623–32.CrossRefPubMedGoogle Scholar