Rapid Immune Recovery and Graft-Versus-Host Disease-Like Engraftment Syndrome After Adoptive Transfer of Costimulated Autologous T Cells

Strategic Insights -

Researchers from the University of Maryland, Marlene and Stewart Greenebaum Cancer Center, have made significant strides in understanding the adoption of costimulated autologous T cells in patients with myeloma. The study, published in Clinical Cancer Research, involved a phase I/II clinical trial with 50 patients, showcasing rapid immune recovery and a subset of patients experiencing graft-versus-host disease-like engraftment syndrome. This groundbreaking research has shed light on the potential of T-cell transfers in augmenting vaccine-specific immune responses.

Key Takeaways:

  • The study involved a phase I/II clinical trial with 50 patients, divided into two arms (A and B) with different immunization regimens.
  • The mean number of T cells infused was 4.26 x 10^10 (range, 1.59-5.0), with a significant increase in CD3, CD4, and CD8 counts at day 14 after transplant.
  • Eight patients (16%) developed a T-cell "engraftment syndrome" clinically and histopathologically indistinguishable from grade 1-3 acute graft-versus-host disease (GVHD) of the gastrointestinal tract and/or grade 1-2 cutaneous GVHD.
  • T-cell infusions were well tolerated, with no effect on hematopoietic recovery.
  • Robust vaccine-specific B- and T-cell responses were generated, demonstrating the efficacy of adoptive T-cell transfers.

Statistics:

  • 50 patients participated in the clinical trial (25 in arm A and 25 in arm B).
  • The mean number of T cells infused was 4.26 x 10^10.
  • 16% of patients (8 out of 50) developed a T-cell engraftment syndrome.
  • CD3, CD4, and CD8 counts at day 14 after transplant were 4,198, 1,545, and 2,858 cells/μL, respectively.
  • Interleukin (IL)-6 and IL-15 levels increased early after transplant, and IL-15 levels correlated significantly with day 14 T-cell counts.

Sources:

  • Rapoport, A. P., et al. (2009). Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of Costimulated autologous T cells. Clinical Cancer Research, 15(13), 4499-4507.
  • University of Maryland, Marlene and Stewart Greenebaum Cancer Center
  • American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA