Immunological effects in patients with steroid-refractory graft-versus-host disease following treatment with basiliximab, a CD25 monoclonal antibody.
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.
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Geothy
G
Chakupurakal
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
María Alejandra
MA
García-Márquez
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Alexander
A
Shimabukuro-Vornhagen
Max-Planck-Institute for Metabolism, Research, Cologne, Germany.
Sebastian
S
Theurich
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Udo
U
Holtick
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Michael
M
Hallek
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Christof
C
Scheid
Interventional Immunology Group, Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Michael
M
von Bergwelt-Baildon
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D000077552:Basiliximab; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013256:Steroids / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019172:Transplantation Conditioning / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D013256:Steroids; D000077552:Basiliximab
CD25 monoclonal antibody; allogeneic stem cell transplantation; basiliximab; steroid-refractory graft-versus-host disease