Low response rates (range: 0-33%) were reported in acute lymphoblastic leukemia (ALL) patients who relapsed after bone marrow transplantation (BMT) and received donor leukocyte infusions (DLI). We describe an ALL patient who presented with a relapse in blood, bone marrow, breast, and axillary nodes 3 months after BMT from an unrelated donor. She achieved a second hematological complete remission (CR) after chemotherapy, with persistence of MLL-AF4 transcript in the bone marrow. DLI induced a long-lasting molecular CR that persisted on day 630 of DLI and was associated with a grade III graft-versus-host disease, which was controlled by prednisone, cyclosporine, and infliximab. This case report suggests the existence of an important graft-versus-leukemia (GVL) effect in patients with ALL and adds evidence for the activity of DLI towards extrahematological recurrences and ALL patients carrying t(4;11).