Immunological effects in patients with steroid-refractory graft-versus-host disease following treatment with basiliximab, a CD25 monoclonal antibody

Eur J Haematol. 2016 Aug;97(2):121-7. doi: 10.1111/ejh.12691. Epub 2015 Nov 16.

Abstract

Steroid-refractory graft-versus-host disease (GvHD) is a complication following an allogeneic stem cell transplantation with limited therapeutic options. Studies have shown a response in up to 80% of patients with this condition after treatment with the CD25 monoclonal antibody, basiliximab. Despite the good responses to treatment, around 50% of the patients experience recurrence of their GvHD symptoms 4-6 wk following cessation of therapy. The in vivo changes in the following treatment with this antibody have not been elucidated so far. We treated 14 patients with severe steroid-refractory GvHD with basiliximab weekly for 4 wk and monitored the changes in the T-, B-, NK- and dendritic cell subsets over this time period. The overall response to treatment was 92% (13/14) with 50% (7/14) achieving a complete response. Fifty four percentage (7/13) of the patients who responded showed recurrence of their GvHD symptoms. Contrary to expectations, our observations showed a significant depletion of the regulatory T-cell subset following treatment. Our findings suggest that the undesirable depletion of the regulatory T cells along with the CD25(+) acute inflammatory cells might be responsible for the high incidence of GvHD recurrence in this cohort of patients.

Keywords: CD25 monoclonal antibody; allogeneic stem cell transplantation; basiliximab; steroid-refractory graft-versus-host disease.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Basiliximab
  • Drug Resistance
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / etiology*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / therapeutic use*
  • Steroids / therapeutic use
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transplantation Conditioning / adverse effects
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Recombinant Fusion Proteins
  • Steroids
  • Basiliximab