T lymphocyte reconstitution following preemptive donor leukocyte infusion therapy forpatientsathigh risk for relapse following T cell depleted bone marrow transplantation from a partially mismatched related donor

Academic Article

Abstract

  • New therapies, such as donor leukocyte infusions (DLI), for relapsed leukemia, have increased the possibility of cure for patients (pts) wtio fail BUT. Since T cell depletion of the graft (TCD) can be associated with an increased risk of relapse, we developed a protocol in which leukocytes from the pts' partially mismatched related donor (PMRD) were infused preemptively at intervals following TCD BMT This study compares functional, phenotypic, and molecular recovery of T cells in pts receiving preemptive DLI to mat in pts on an identical protocol who were not treated with DLI. An increase in the proportion and absolute number of CD3+ lymphocytes was seen in the DLI group, with a preferential increase in the CD3+CD8+ phenotype. The greatest degree of T cell expansion occurred in pts who received DL! and also developed acute grafl-versus-host disease (aGvHD) >Grade II. However, these changes may be primarily associated with aGvHD. since they were also seen in non-DLl pts who developed >Grade II aGvHD. Non-stimulated expression of the early activation marker CD69 on CD3+CD4+ cells was reduced compared to normal controls (healthy marrow donors) at aH time points, but expression on CD3+CD8+ cells at day +45 post-BMT was the same as that of controls. There was no difference in T cell response to PHA (measured both by CD69 expression and W-Thymktine uptake) in the DLI and non-DLl groups at day +60 post-BMT, however, the response in both groups was markedly less than in the controls. There were no significant differences between the groups with respect to expression of CD57, CD28, and HLA-DR on CD3+ T cells, and reconstitution of TCR-V. In summary, DLI from PMRO increased the proportion and number of CD3+CD8+ T cells, but did not result a shift to a CD3+ cytotoxk; phenotype, nor increased expression of CD69 or Class II. or enhanced recovery of the TCR-V repertoire diversity. Although follow-up is short, these data may explain why we have not been able to detect a significant clinical difference in relapse between the DU and non-DLl groups.
  • Published In

    Author List

  • Lamb LS
  • Start Page

  • 1091
  • Volume

  • 24
  • Issue

  • 9