title: Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study.
abstract: Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CR+PR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p= 0.043, RR = 3.169), development of grades III-IV liver aGVHD (p= 0.007, RR = 5.034) and cytomegalovirus (CMV) reactivation (p= 0.035, RR = 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%,p<0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yamin
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command (Guangzhou Liuhuaqiao Hospital) , Guangzhou, Guangdong Province, P.R. China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Soochow University , Suzhou, Jiangsu Province, P.R. China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Hematology, Zhejiang Provincial People's Hospital , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Lan
authors.affiliation: Department of Hematology, Nanfang Hospital of Southern Medical University , Guangzhou, Guangdong Province, P.R. China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Jingsong
authors.initials: J
authors.lastname: He
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Lai
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Du
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Han
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wei
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang Province, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
keywords: Basiliximab; etanercept; hematopoietic stem cell transplantation; steroid-refractory acute GVHD