Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation.

Journal Article (Journal Article)

Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells. Sixteen adult patients received a prophylactic DLI at a median of 113 days (range 76-280 days) following an HLA-identical, non-myeloablative allogeneic hematopoietic stem cell transplantation. Three patients each received the naive T-cell depleted DLI with a CD3+ dose of 1 × 105/kg, 1 × 106/kg, and 5 × 106/kg. The maximum dose of 1 × 107/kg was expanded to 7 patients. No dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI were observed at any dose level. One patient developed grade 2 acute GvHD of skin and upper intestines, and another developed moderate chronic GvHD of the lungs following the DLI. With a median follow-up of 2.8 years, 2-year progression-free and overall survival is 50.0% and 68.8%, respectively. In conclusion, these data suggest that a DLI that has been depleted of CD45RA+ naive T cells is feasible and carries a low risk of acute or chronic GvHD.

Full Text

Duke Authors

Cited Authors

  • Maung, KK; Chen, BJ; Barak, I; Li, Z; Rizzieri, DA; Gasparetto, C; Sullivan, KM; Long, GD; Engemann, AM; Waters-Pick, B; Nichols, KR; Lopez, R; Kang, Y; Sarantopoulos, S; Sung, AD; Chao, NJ; Horwitz, ME

Published Date

  • January 2021

Published In

Volume / Issue

  • 56 / 1

Start / End Page

  • 137 - 143

PubMed ID

  • 32624583

Electronic International Standard Serial Number (EISSN)

  • 1476-5365

Digital Object Identifier (DOI)

  • 10.1038/s41409-020-0991-5


  • eng

Conference Location

  • England