Immunogenetic Cross-Talk in Patients Transplanted for AML: CMV Reactivation Is Not a Strong Stimulus for Immune Response Against Leukemia

Abstract

and cytokine levels were associated with acute GVHD (IL-7) or pattern of immune reconstitution (IL-15). However, it is not known whether recipients of lower-intensity conditioning or sirolimus-based GVHD prophylaxis have variable levels of these cytokines or whether such potential cytokine variability is associated with clinical outcome. To begin to address this, we measured multiple cytokine levels (MesoScale multiplex assay; current analysis restricted to IL-7 and IL-15 levels at day 0 of transplant) in recipients of low-intensity conditioning (Flu/Cy; total Cy dose, 1200 mg/m 2 ; see Table 1). Patients received GVHD prophylaxis consisting of cyclosporine plus shortcourse sirolimus (d2 through d14 post-SCT) at either standard-dose (n¼46; "SD Cohort") or high-dose (n¼20; "HD Cohort") (target trough level: 5-10 or 20-30 ng/ml, respectively). All patients received pre-emptive DLI consisting of rapamycin-resistant T cells (Fowler et al; Blood, 2013); however, in the current study, T cell manufacturing was reduced from 12 days to 6 days. Clinical outcomes (Table 1) were similar in SD and HD Cohorts, including: donor T cell and myeloid cell chimerism pre-DLI (d14 post-SCT) and post-DLI (d28 post-SCT), and incidence of classical acute GVHD. Remarkably, a wide range of IL-7 and IL-15 values were detected at day 0 of SCT in both SD and HD Cohorts