title: Rituximab-based treatments followed by adoptive cellular immunotherapy for biopsy-proven EBV-associated post-transplant lymphoproliferative disease in recipients of allogeneic hematopoietic stem cell transplantation.
abstract: To improve prognosis of post-transplant lymphoproliferative disease (PTLD), a sequential therapeutic strategy that rituximab-based treatments followed by donor lymphocyte infusion (DLI) or autologous EBV-specific cytotoxic T lymphocytes (EBV-CTL) for biopsy-proven EBV-associated PTLD in recipients of allogeneic hematopoietic stem cell transplantation was designed. 84 patients with EBV-PTLD were enrolled in this prospective study. After two cycles of the rituximab-based treatments, 68 of 84 patients (81% [95% CI 71-88]) responded and 52 (62% [51-72]) had CRs. This increased to 73 of 77 patients (95% [87-98]) with completion of sequential cell infusions, and 70 of 77 (91% [82-96]) achieved CRs after DLI or autologous EBV-CTL infusion. 22 patients experienced acute GVHD (aGVHD) (grade I in 5 and grade II in 13, grade III in 4) and 13 chronic GVHD (limited cGVHD in 7 and extensive cGVHD in 6) in 62 patients undergoing a median of three doses of DLI. The incidences of GVHD were similar between DLI and EBV-CTL group (aGVHD 35% vs. 33%, p = 0.876; cGVHD 21% vs. 13%; p = 0.503). EBV-CTL activity after the rituximab-based treatments did not change, while increased after cell infusions and reached its maximum in the 3rd or 6th month after EBV-CTL or DLI treatment, respectively. The 5-y cumulative incidence of PTLD relapse was 4.5% ± 3.3%. The 5-y overall survival (OS) and progression-free survival (PFS) after PTLD were 70.7% ± 5.2% and 68.9% ± 5.3%, respectively. Rituximab-based treatments combined with adoptive cellular immunotherapy might elevate CR rates and reduce relapse of PTLD after allo-HSCT.
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institution of Hematology, People's Hospital, Peking University , Beijing, China.
authors.forename: Lanping
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.affiliation: Institution of Hematology, People's Hospital, Peking University , Beijing, China.
authors.forename: Daihong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institution of Hematology, Zhujiang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Song
authors.affiliation: The First People's Hospital of Chenzhou , Chenzhou, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xuan
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Wu
authors.affiliation: Institution of Hematology, People's Hospital, Peking University , Beijing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institution of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
keywords: Adoptive cellular immunotherapy; EBV; EBV-CTL; PTLD; donor lymphocyte infusion; hematopoietic stem cell transplantation; relapse; rituximab