title: T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation.
abstract: The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, developed hyperacute SR-GVHD. We report on the outcome of two different regimens for treatment of SR-GVHD on the outcome of these patients. Five patients were treated in Regimen A consisting of anti-thymocyte globulin, Etanercept and Basiliximab. The next 5 patients were treated combining T cell costimulation blockade with Abatacept along with Etanercept and Basiliximab. The overall response at days 29 and 56 were 40% and 0% with Regimen A and100% and 40% with Regimen B. The major cause of treatment failure was progression of GVHD and opportunistic infections. Two of the patients achieving a complete remission on Regimen B are long term disease free survivors off immunosuppression. Our study demonstrates the dismal outcome of early onset SR-GVHD in children following T replete haploidentical transplantation. However, the combination of Abatacept with anticytokine agents seems to produce encouraging early response and might warrant further investigation.
authors: Manashi Chakrabarti Foundation, Kolkata, India; Department Of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India. Electronic address: drsaritaranij@gmail.com.
authors: Sarita Rani
authors: SR
authors: Jaiswal
authors: Department Of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors: Shamsuz
authors: S
authors: Zaman
authors: Manashi Chakrabarti Foundation, Kolkata, India.
authors: Aditi
authors: A
authors: Chakrabarti
authors: Department Of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors: Amit
authors: A
authors: Sehrawat
authors: Department Of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors: Satish
authors: S
authors: Bansal
authors: Department Of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors: Mahesh
authors: M
authors: Gupta
authors: Manashi Chakrabarti Foundation, Kolkata, India; Department Of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors: Suparno
authors: S
authors: Chakrabarti
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D000208:Acute Disease; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000077552:Basiliximab; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D018572:Disease-Free Survival; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013256:Steroids / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D000075442:Transplantation, Haploidentical; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D016207:Cytokines; D011993:Recombinant Fusion Proteins; D013256:Steroids; D000069594:Abatacept; D000077552:Basiliximab; D000068800:Etanercept
keywords: Costimulation blockade; GVHD; Haploidentical; Pediatric; Steroid-refractory