After May 2012, we modified the inclusion criteria of protocol for patients that underwent HLA-MSD to keep the uniformity from the clinical trial. Study design All sufferers were assigned to either the IL-2 arm or control arm post-transplantation randomly. more prevalent in the IL-2 arm set alongside the control arm (36% [range 29C44%] vs. 15% [vary 10C20%], = 0.03). The cumulative occurrence of moderate-to-severe persistent GVHD (cGVHD) was low in the IL-2 arm set alongside the control arm (33% [range 26C39%] vs. 57% [range MK-0517 (Fosaprepitant) 49C64%), = 0.02). Therefore, the 3-y GVHD-free and GVHD progression-free survival (GPFS) rates were significantly higher MK-0517 (Fosaprepitant) in the IL-2 arm compared to the control arm (47% [range 39C55%] vs. 31% [range 25C38%], = 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. = 2), a positive MRD test (= 2), or severe contamination (= 1). Of the enrolled subjects, 43 were randomized to receive IL-2 treatment and the remaining 47 were assigned to the control cohort. Open in a separate window Physique 1. Flowchart of study design and individual enrollment. The two groups had comparative individual and donor characteristics (Table?1). Median follow-up was 1234 d (range, 587C1596 d). All of the subjects in the IL-2 cohort received 1 cycle of IL-2; 29 received 4 cycles. The detailed flowchart of patients enrolled in the IL-2 and control arms of this trial and their reasons for exiting the study has been explained in Fig.?S1. Table 1. Patient and donor characteristics. value= 0.20; Fig.?2A and Table?3) in the control arm. Of nine subjects with a prior positive MRD test in the IL-2 arm, six relapsed, MK-0517 (Fosaprepitant) as did three of five subjects with a prior positive MRD test in the control arm. Open in a separate window Physique 2. The clinical outcomes between the IL-2 and control arms. (A) Relapse, (B) non-relapse mortality (NRM), (C) minimal residual disease (MRD), (D) moderate-to-severe chronic GVHD, (E) overall survival (OS) and (F) GVHD-free and relapse-free survival (GPFS). Patient cohorts: IL-2 group (= 43) and control group (= 47). Table 3. Incidence of adverse events and transplantation outcomes for patients who underwent allogeneic stem cell transplantation. value= 0.038). MK-0517 (Fosaprepitant) Five subjects died of severe cGVHD (IL-2 cohort = 1; control cohort = 4). Three other subjects died of CMV-related hepatitis, HBV-related hepatitis, and lung contamination. The median intervals to NRM were 336 d in the IL-2 cohort and 321 d in the control cohort (range, 73C819 d). The NRM rates were lower in the IL-2 cohort than in the control arm (2% (range 0C5%) vs. 15% (range 10C21%); = 0.038; Fig.?2B and Table?3). Positive MRD assessments Twenty subjects became MRD+, including fifteen in the IL-2 cohort and seven in the control cohort. The median intervals from randomization to a positive MRD test was 198 d (range, 90C1093 d) in the IL-2 cohort and 166 d (range, 83C360 d) in the control cohort (= 0.745). The cumulative incidence of a positive MRD test was higher in IL-2 cohort compared with the control cohort (38% [range 29C44%] vs. 15% [range 10C20%]; = 0.03; Fig.?2C). Multivariate analysis showed that IL-2 treatment during the early post-transplantation period significantly increased the incidence of positive MRD assessments compared with the control arm (hazard ratio [HR] = 3.3; 95% CI, 1.2C9.1; = 0.022; Table?3). The interventions for recurrent leukemia and a positive MRD test are shown in Fig.?S2. cGVHD status A total of 23 subjects in the IL-2 cohort developed cGVHD compared with 30 subjects in the control cohort. Median intervals to developing cGVHD were 186 d in the IL-2 cohort and 197 d in the control cohort. The cumulative incidences of all stages of cGVHD were Rabbit Polyclonal to U51 53% [range 46C61%] vs. 65% [range 58C72%] (= 0.33), but the cumulative incidence of moderate-to-severe cGVHD was lower in the IL-2 cohort (33% [range 26C39%] vs. 56% [range 49C64%]; = 0.02; Fig.?2D). Multivariate analysis showed that IL-2 treatment during the early post-transplantation period significantly decreased the incidence of moderate-to-severe cGVHD compared with the control arm (HR = 0.5; 95% CI, 0.3C0.9; = 0.033;.