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In Vivo T Cell Costimulation Blockade with Abatacept for Acute Graft-versus-Host Disease Prevention: A First-in-Disease Trial
- Source :
- Biology of Blood and Marrow Transplantation. 19:1638-1649
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- 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
- Subjects :
- Adult
Male
musculoskeletal diseases
medicine.medical_specialty
Immunoconjugates
Transplantation Conditioning
Adolescent
T-Lymphocytes
T cell
Graft vs Host Disease
Gastroenterology
Abatacept
Young Adult
Costimulation blockade
Internal medicine
Humans
Transplantation, Homologous
Medicine
Aged
Transplantation
business.industry
Hematopoietic Stem Cell Transplantation
Hematology
Graft-versus-host disease prophylaxis
Middle Aged
Blockade
surgical procedures, operative
medicine.anatomical_structure
Allogeneic transplantation
Pharmacodynamics
Acute Disease
Cohort
Immunology
Feasibility Studies
Female
Methotrexate
business
Immunosuppressive Agents
CD80
medicine.drug
Subjects
Details
- ISSN :
- 10838791
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Biology of Blood and Marrow Transplantation
- Accession number :
- edsair.doi.dedup.....8350820a43c10a5af3cfa2474a5841f2
- Full Text :
- https://doi.org/10.1016/j.bbmt.2013.09.003