title: Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study.
abstract: Leukemia relapse and chronic graft-versus-host disease (cGVHD) are still major obstacles of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The numbers and activity of natural killer (NK) and T-regulatory cells can be increased post-transplantation by exposure to interleukin-2 (IL-2). We tested whether administering low-dose IL-2 would decrease leukemia relapse while reducing cGVHD after allotransplantation. This controlled, open-label randomized trial included 90 recipients of allotransplants. Subjects were randomized in a 1:1 ratio to either receive or not receive low-dose IL-2 during the early post-transplantation period. Patients in the IL-2 arm received a subcutaneous injection of low-dose IL-2 (1×106U/d) on day 60 after allo-HSCT. IL-2 was administered daily for 14 d followed by a 14-d hiatus. The primary endpoint was the cumulative incidence of leukemia relapse (CIR). Three-year CIRs for the IL-2 arm and control arm were 23% (range 16-30%) and 11% (range 6-15%;p= 0.20), respectively. Minimal residual disease-positive (MRD+) tests were more common in the IL-2 arm compared to the control arm (36% [range 29-44%] vs. 15% [range 10-20%],p= 0.03). The cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) was lower in the IL-2 arm compared to the control arm (33% [range 26-39%] vs. 57% [range 49-64%),p= 0.02). Therefore, the 3-y GVHD-free and GVHD progression-free survival (GPFS) rates were significantly higher in the IL-2 arm compared to the control arm (47% [range 39-55%] vs. 31% [range 25-38%],p= 0.048). Blood Tregs, NK cells, and NK-cell cytotoxicity were increased in subjects in the IL-2 arm between 3 mo and 6 mo post-transplantation. Administration of low-dose IL-2 during the immediate post-transplantation period was associated with a higher GPFS but did not decrease the CIR.
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Zhao
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Yu-Tong
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Yan
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Feng-Rong
authors.initials: FR
authors.lastname: Wang
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
keywords: IL-2; MRD; NK; Treg; cGVHD