On. Similarly, the use of MSC was not associated with decreased 15900046 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) 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 AZ 876 site 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 AN-3199 stromal cells) as demonstrated by the persistence of median ALC counts of 110 cells/mL at the time of transplantation. Although the first T cell chimerism assessment in current patient was usually around day 28 after HSCT, a prior study analyzing data from patients given similar conditioning regimen demonstrated that a median of 50 CD3+ T cells of recipient origin/mL persisted on day 14 after HSCT [40]. Further, as observed by other groups of investigators [46,51,52], there was a strong inverse correlation between IL-7 levels and absolute lymphocyte counts [46,52], as well as a strong inverse correlation between IL-7 levels and T cell subsets on days 14 and 28 after transplantation. Other factors associated with IL-7 levels included high CRP levels, and low numbers of transplanted T cells. Levels of IL-7 in current nonmyeloablative recipients where lower to what was observed by Thiant et al. in a cohort of 45 patients given grafts after fludarabine +2 Gy TBI (n = 18) or more intense but still reduced-intensity conditioning (n = 27) [52], and where much lower than what was observed by Dean et al. in patients given grafts after sequential chemotherapy followed by a chemotherapy/fludarabine-based reduced-int.On. Similarly, the use of MSC was not associated with decreased 15900046 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) 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 transplantation. Although the first T cell chimerism assessment in current patient was usually around day 28 after HSCT, a prior study analyzing data from patients given similar conditioning regimen demonstrated that a median of 50 CD3+ T cells of recipient origin/mL persisted on day 14 after HSCT [40]. Further, as observed by other groups of investigators [46,51,52], there was a strong inverse correlation between IL-7 levels and absolute lymphocyte counts [46,52], as well as a strong inverse correlation between IL-7 levels and T cell subsets on days 14 and 28 after transplantation. Other factors associated with IL-7 levels included high CRP levels, and low numbers of transplanted T cells. Levels of IL-7 in current nonmyeloablative recipients where lower to what was observed by Thiant et al. in a cohort of 45 patients given grafts after fludarabine +2 Gy TBI (n = 18) or more intense but still reduced-intensity conditioning (n = 27) [52], and where much lower than what was observed by Dean et al. in patients given grafts after sequential chemotherapy followed by a chemotherapy/fludarabine-based reduced-int.
