Intentional donor lymphocyte-induced limited acute graft-versus-host disease is essential for long-term survival of relapsed acute myeloid leukemia after allogeneic stem cell transplantation

The prognosis of patients with relapsed acute myeloid leukemia after allogeneic transplantation is poor. We hypothesized that initial disease control by effective cytoreduction, followed by rapid induction of a profound allo-immune response by donor-lymphocyte infusion during the neutropenic phase, is essential for long-term survival. Additional interferon-α was administered when no acute graft-versus-host-disease occurred within 3 weeks after donor-lymphocyte infusion. Overall, 44 patients with relapsed acute myeloid leukemia were assessed; 26 had relapsed after myeloablative conditioning and 18 after reduced-intensity conditioning. Of these 44 patients, seven were not eligible for cytoreductive treatment because of poor performance status (n=3) or severe graft-versus-host-disease (n=4) at the time of relapse. Patients with smoldering relapses (n=5) received donor-lymphocyte infusion only. Thirty-two patients received cytoreductive treatment, followed by donor-lymphocyte infusion in 22 patients. Reasons for not receiving donor-lymphocyte infusion were chemotherapy-related death (n=1) and chemotherapy-refractory disease (n=9). The 2-year overall survival rate after donor-lymphocyte infusion was 36% (95% confidence-interval: 16-57%). The impact of acute graft-versus-host-disease on survival was calculated with a Cox-regression model including onset of acute graft-versus-host-disease as a time-dependent variable. Development of grade 1-3, but not grade 4, acute graft-versus-host-disease was associated with superior survival as compared to absence of graft-versus-host-disease (hazard ratio 0.22, P=0.03). In conclusion, efficient cytoreduction followed by donor-lymphocyte infusion and subsequent interferon-α leading to limited acute graft-versus-host-disease represents a potentially curative option for patients with relapsed acute myeloid leukemia after allogeneic transplantation.