GM-CSF + INF-alpha induce a graft-versus-leukemia effect in BMT patients with relapsed AML and ALL

Abstract

6634 Background: Relapse of acute leukemia following allogeneic hematopoietic progenitor cell transplantation (HPCT) has a poor prognosis. Second HPCT and donor leukocyte infusions have significant toxicity with limited effectiveness. GM-CSF and Interferon-alpha (IFN) activate dendritic cells and induce leukemia cells to express co-stimulatory molecules and enhance allo-antigen presentation, potentially inducing graft-versus-leukemia effects. We hypothesized GM-CSF and IFN induce anti-leukemic effects in patients with relapsed acute leukemia. Methods: We performed a single institution retrospective study of 97 patients with AML or ALL relapsed after allogeneic HPCT. The dose and duration of cytokines, toxicities, response, and post-relapse survival were analyzed. Overall survival rates of cytokine-treated patients were compared with relapsed leukemia patients who did not receive cytokine immunotherapy. Results: Six patients received GM-CSF and IFN injections following the diagnosis of ALL or AML relapsed after allogeneic HPCT. The median dose of GM-CSF was 500 ug administered 3 times per week (median of 6 doses). The median dose of IFN was 3 million units administered 1–3 times per week (median of 6 doses). Four of the 6 patients (67%) exhibited a pathologic or hematologic remission with an average response of 3.3 mos. (range 6 wks. to 12 mos.) Toxicities included malaise, myalgias, and fever. GVHD was documented in 4 out of the 6 patients, and occurred at a median of 6 weeks after beginning cytokine immunotherapy. The median survival of cytokine-treated patients was 130 days with 3/6 patients remaining alive at a median follow-up of 373 days. Two of 3 surviving patients remain without evidence of disease on no immunosuppressive drugs. Cytokine-treated patients had better survival compared to 91 non-cytokine-treated patients with relapsed ALL or AML (median survival of 52 days, one-year survival of 8%, p=0.02). Conclusions: The administration of GM-CSF and IFN may induce remissions in patients with acute leukemia who have relapsed after allogeneic HPCT. Further studies to evaluate the optimal dosing schedule and duration of therapy should be pursued. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen