Induction of GvL after allogeneic stem cell transplantation.

18004 Background: Bone marrow or blood stem cell transplantation remains the only potentially curative therapy for patients with high-risk leukemia, but relapse remains the major cause of treatment failure. We hypothesized that the combination of GM-CSF and IFN-alfa-2b upregulates co-stimulatory molecule expression and down-regulates counter-regulatory signals, leading to a graft vs. leukemia effect. We report on correlative laboratory data from an ongoing prospective clinical trial to assess the efficacy and toxicity of GM-IFN in patients with acute leukemia relapsed after allogeneic transplantation.,Pilot study, target enrollment of 15 patients. Eligible patients are older than 1 year of age, with acute leukemia/MDS relapsed after allogeneic transplantation; adequate organ function, lack of GVHD after withdrawal of immunosuppression, and > 20% donor chimerism in CD3+ cells. Patients with > 5% circulating blasts receive cyto-reductive therapy with either hydroxyurea, or cytarabine 0.5-1gm/m IV daily for 5 days. GM 250mg/m 3x/week and pegylated IFN 1.5mcg/kg weekly are administered to patients who lack significant GVHD after cyto-reductive therapy and after recovery of toxicities. Cytokines are continued until development of GVHD, progression of disease, or limiting toxicity. Study samples collected pre and post-therapy are assessed for co- stimulatory molecules on blasts & T-cells, enumeration of immune cells (Tregs, DCs, and NK cells), intracellular cytokines, and cytotoxicity assays.,6 patients with AML relapsed after allogeneic transplant have been enrolled, median age 20. Median time to relapse 5 months. Paired samples were obtained on 4 patients. One patient progressed and expired prior to therapy, and 1 patient withdrew prior to cytokines. 2 pts. developed GVHD. Three pts. survive at 3, 4, and 5 mos. CD80 was upregulated in blasts, and CTLA4 was downregulated in CD4+T cells and NK cells in all pts. post-therapy. PDL1 was upregulated on blasts in 3/4 pts. post-therapy.,Immune therapy with GM-IFN appears to upregulate co-stimulatory molecules on leukemic blasts, but this seems to be tempered by upregulation of counter-regulatory signals on T-cells. Cytotoxicity assays are being evaluated will be presented. Accrual is ongoing and will be expanded to other centers. No significant financial relationships to disclose.