Prophylactic use of low-dose interleukin-2 early post-transplantation: a randomised study

• Published in: The Lancet (British edition) 2015-10, Vol.386, p.S7-S7
• Main Authors: Zhao, Xiangyu, Zhao, Xiaosu, Wang, Yutong, Chang, Ying-Jun, Xu, Lan-Ping, Zhang, Xiao-Hui, Wang, Yu, Chen, Yu-Hong, Han, Wei, Chen, Huan, Yan, Chen-Hua, Wang, Feng-Rong, Wang, Jing-Zhi, Sun, Yu-Qian, Tang, Fei-Fei, Fu, Hai-Xia, Liu, Kai-Yan, Huang, Xiao-Jun, Prof
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Hematology; Internal Medicine; Leukemia; Research projects; Stem cells; Transplantation
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(15)00585-1

Abstract Background Evidence suggests that natural killer cells and regulatory CD4+ CD25+ FoxP3+ T (Treg ) cells, which are expanded and stimulated by the application of interleukin-2, could mediate protection against graft-versus-host disease (GVHD) while maintaining graft anti-tumour activity. The aim of this study was to confirm that a low dose of interleukin-2 can prevent relapse while reducing chronic GVHD. This study has been presented in part as an oral presentation at the 56th American Society of Hematology Annual Meeting and Exposition (Dec 6, 2014) in San Francisco, CA, USA. Methods In this open-label, prospective, randomised controlled trial in a single centre in China, donor–recipient pairs were randomly assigned (1:1) into the interleukin-2 group and control group by the sub-investigator (treating physician of our transplant centre) according to a computer-generated randomisation system. We enrolled patients (aged ≥15 years) with standard-risk leukaemia (except Ph+ ALL and T-ALL) who had undergone unmanipulated allogeneic stem cell transplantation. The transplantation procedure for control group patients was the same as that of the interleukin-2 group, except for interleukin-2 treatment. Interleukin-2 treatment (daily 1×106 IU/m2 body-surface area) was repeated every 14 days for six courses until disease progression or unacceptable toxicity. The primary endpoint was the cumulative incidence of haematological relapse. The primary efficacy end point was a between-group comparison of the time from transplantation to relapse in the intention-to-treat population (all randomly assigned patients). 360 subjects were estimated to be needed to detect a 10% difference between groups in cumulative incidence of haematological relapse based on our previous results (from 20% to 10%) with a one-sided α of 0·05 and a power of 80%. Futility analyses after a quarter, half, and three-quarters of 360 cases were specified. This study was approved by the Institutional Review Board of Peking University, and written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. This trial is registered with ClinicalTrials.gov , number NCT01517347. Findings Since this study began in January, 2012, we have randomly assigned 43 patients to the interleukin-2 group and 47 patients to the control group. First interim analysis was done when 90 cases were enrolled. The cumulative incidence of haematological relapse of the interleukin-2 and con