Els among nonmyeloablative recipients (P = 0.8) (C). Cumulative incidence of grade II

Els among nonmyeloablative recipients (P = 0.8) (C). Cumulative incidence of grade II V acute GVHD according to day 14 IL-15 serum levels among nonmyeloablative recipients (P = 0.6) (D). doi:10.1371/journal.pone.0055876.gincidence of grade II V acute GVHD was 19 in patients with day 14 IL-7 levels.median (5.2 pg/mL) versus 37 in patients with day 14 IL-7 levels # median (P = 0.18) (Figure 3B). The 180-day cumulative incidence of grade II V acute GVHD was 24 in patients with day 7 IL-15 levels.median (12.5 pg/ mL) versus 28 in patients with day 7 IL-15 levels # median (P = 0.8) (Figure 3C). Similarly, the 180-day cumulative incidence of grade II V acute GVHD was 25 in patients with day 14 IL15 levels.median (10.5 pg/mL) versus 33 in patients with day 14 IL-15 levels # median (P = 0.8) (Figure 3D). Finally, in a multivariate Cox model, neither median IL-7 levels (P = 0.17 with a trend for an inverse correlation) on days 7?4 nor median IL-15 levels (P = 0.21 with a trend for a positive correlation) on days 7?4 correlated with occurrence of grade II V acute GVHD the first 200 days after transplantation. Similarly, the use of MSC was not associated with decreased incidence of grade II V acute GVHD. This could be explained by the fact that all 23 MSC recipients versus of 9 of the remaining 49 patients (18 ) received PBSC from HLA-mismatched donors. None of the other factors tested (dose of TBI, donor type, female donor to male recipient versus other gender combination, patient age, and donor age) 1662274 were significantly associated with the incidence of grade II V acute GVHD in the current study.IL-15 Levels did not Predict for Subsequent Relapse/ ProgressionGiven that a previous publication showed an association between high IL-15 levels and low risk of relapse/progression [46], we compared the cumulative incidence of relapse/progression according to IL-15 levels 14 days after transplantation in our cohort of patients. The 6-month and 1-year cumulative incidences of relapse/progression were 29 and 32 , respectively, in patients with day 14 IL-15 levels.median (10.5 pg/mL) versus 37 and 46 , respectively, in patients with day 14 IL-15 levels # median (P = 0.57).DiscussionFollowing allo-HSCT, eradication of residual tumor cells depends in part (in case of high-dose conditioning) or mainly (in case of nonmyeloablative conditioning) on immune-mediated graft-versus-tumor effects [1,2,4]. Prior studies have demonstrated a close relationship between T cell reconstitution and graft-versustumor effects after allo-HSCT [4,14,47?9]. Given that HPE allows the expansion of potentially alloreactive T cell clones, it has been generally accepted that HPE plays a major role in graftversus-tumor effects, but could also cause or favor acute GVHD.IL-7 and IL-15 after Allo-HSCTThis prompted us to investigate the kinetics of IL-7 and IL-15 levels in a cohort of 70 patients given grafts after truly nonmyeloablative conditioning. First, patients given grafts after nonmyeloablative Madrasin chemical information conditioning had only a modest (,2 fold) increase of IL-7 levels after transplantation (contrarily to what we observed in another cohort of patients given grafts after myeloablative conditioning [50]), that persisted up to day 21. This is probably due to the fact that nonmyeloablative patients experienced relatively mild AN 3199 site lymphopenia (and thus continue to consume the IL-7 produced by stromal cells) as demonstrated by the persistence of median ALC counts of 110 cells/mL at the time of tra.Els among nonmyeloablative recipients (P = 0.8) (C). Cumulative incidence of grade II V acute GVHD according to day 14 IL-15 serum levels among nonmyeloablative recipients (P = 0.6) (D). doi:10.1371/journal.pone.0055876.gincidence of grade II V acute GVHD was 19 in patients with day 14 IL-7 levels.median (5.2 pg/mL) versus 37 in patients with day 14 IL-7 levels # median (P = 0.18) (Figure 3B). The 180-day cumulative incidence of grade II V acute GVHD was 24 in patients with day 7 IL-15 levels.median (12.5 pg/ mL) versus 28 in patients with day 7 IL-15 levels # median (P = 0.8) (Figure 3C). Similarly, the 180-day cumulative incidence of grade II V acute GVHD was 25 in patients with day 14 IL15 levels.median (10.5 pg/mL) versus 33 in patients with day 14 IL-15 levels # median (P = 0.8) (Figure 3D). Finally, in a multivariate Cox model, neither median IL-7 levels (P = 0.17 with a trend for an inverse correlation) on days 7?4 nor median IL-15 levels (P = 0.21 with a trend for a positive correlation) on days 7?4 correlated with occurrence of grade II V acute GVHD the first 200 days after transplantation. Similarly, the use of MSC was not associated with decreased incidence of grade II V acute GVHD. This could be explained by the fact that all 23 MSC recipients versus of 9 of the remaining 49 patients (18 ) received PBSC from HLA-mismatched donors. None of the other factors tested (dose of TBI, donor type, female donor to male recipient versus other gender combination, patient age, and donor age) 1662274 were significantly associated with the incidence of grade II V acute GVHD in the current study.IL-15 Levels did not Predict for Subsequent Relapse/ ProgressionGiven that a previous publication showed an association between high IL-15 levels and low risk of relapse/progression [46], we compared the cumulative incidence of relapse/progression according to IL-15 levels 14 days after transplantation in our cohort of patients. The 6-month and 1-year cumulative incidences of relapse/progression were 29 and 32 , respectively, in patients with day 14 IL-15 levels.median (10.5 pg/mL) versus 37 and 46 , respectively, in patients with day 14 IL-15 levels # median (P = 0.57).DiscussionFollowing allo-HSCT, eradication of residual tumor cells depends in part (in case of high-dose conditioning) or mainly (in case of nonmyeloablative conditioning) on immune-mediated graft-versus-tumor effects [1,2,4]. Prior studies have demonstrated a close relationship between T cell reconstitution and graft-versustumor effects after allo-HSCT [4,14,47?9]. Given that HPE allows the expansion of potentially alloreactive T cell clones, it has been generally accepted that HPE plays a major role in graftversus-tumor effects, but could also cause or favor acute GVHD.IL-7 and IL-15 after Allo-HSCTThis prompted us to investigate the kinetics of IL-7 and IL-15 levels in a cohort of 70 patients given grafts after truly nonmyeloablative conditioning. First, patients given grafts after nonmyeloablative conditioning had only a modest (,2 fold) increase of IL-7 levels after transplantation (contrarily to what we observed in another cohort of patients given grafts after myeloablative conditioning [50]), that persisted up to day 21. This is probably due to the fact that nonmyeloablative patients experienced relatively mild lymphopenia (and thus continue to consume the IL-7 produced by stromal cells) as demonstrated by the persistence of median ALC counts of 110 cells/mL at the time of tra.