In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial

Biol Blood Marrow Transplant. 2013 Nov;19(11):1638-49. doi: 10.1016/j.bbmt.2013.09.003. Epub 2013 Sep 15.


We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P < .01). The ABA patients demonstrated a low rate of aGVHD, despite robust immune reconstitution, with 2 of 10 patients diagnosed with grade II-IV aGVHD before day +100, no deaths from infection, no day +100 TRM, and with 7 of 10 evaluable patients surviving (median follow-up, 16 months). These results suggest that costimulation blockade with abatacept can significantly affect CD4(+) T cell proliferation and activation post-transplantation, and may be an important adjunct to standard immunoprophylaxis for aGVHD in patients undergoing unrelated-donor HCT.

Keywords: Allogeneic transplantation; Costimulation blockade; Graft-versus-host disease prophylaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Feasibility Studies
  • Female
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunoconjugates / therapeutic use*
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Young Adult


  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept