Over-expression of PD-1 Does Not Predict Leukemic Relapse after Allogeneic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2019 Feb;25(2):216-222. doi: 10.1016/j.bbmt.2018.09.037. Epub 2018 Oct 4.


Blockade of the T-cell exhaustion marker PD-1 to re-energize the immune response is emerging as a promising cancer treatment. Relapse of hematologic malignancy after allogeneic stem cell transplantation limits the success of this approach, and PD-1 blockade may hold therapeutic promise. However, PD-1 expression and its relationship with post-transplant relapse is poorly described. Because the donor immunity is activated by alloresponses, PD-1 expression may differ from nontransplanted individuals, and PD-1 blockade could risk graft-versus-host disease. Here we analyzed T-cell exhaustion marker kinetics and their relationship with leukemia relapse in 85 patients undergoing myeloablative T-cell-depleted HLA-matched stem cell transplantation. At a median follow-up of 3.5 years, 35 (44%) patients relapsed. PD-1 expression in CD4 and CD8 T cells was comparably elevated in relapsed and nonrelapsed cohorts. Helios+ regulatory T cells and CD8 effector memory cells at day 30 emerged as independent predictors of relapse. Although leukemia antigen-specific T cells did not overexpress PD-1, single-cell analysis revealed LAG3 and TIM3 overexpression at relapse. These findings indicate that PD-1 is an unreliable marker for leukemia-specific T-cell exhaustion in relapsing patients but implies other exhaustion markers and suppressor cells as relapse biomarkers.

Keywords: Biomarker; Graft-versus-leukemia effect; Post-transplant relapse.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Allografts
  • Biomarkers, Tumor / immunology*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Leukemic / immunology*
  • Humans
  • Leukemia* / immunology
  • Leukemia* / mortality
  • Leukemia* / pathology
  • Leukemia* / therapy
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Programmed Cell Death 1 Receptor / immunology*
  • Recurrence
  • Stem Cell Transplantation*
  • Survival Rate


  • Biomarkers, Tumor
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor