We analyzed toxicity and efficacy of chemotherapy (CT) or second stem cell transplantation (SCT) and/or immunotherapy defined as stop of immunosuppression (IS) or donor leukocyte infusion (DLI) in 47 patients relapsing with acute leukemia. Ten patients received no treatment and 14 patients were treated with CT only. In 12 patients IS was stopped and three of them received additional CT. Five patients received DLI after CT as consolidation and one patient as frontline therapy. Five patients received a second SCT. Median overall survival after relapse was 2 months for the untreated patients, 2 months for patients receiving CT only, 2 months in patients after cessation of IS, 17 months in DLI treated patients and three months in patients receiving a second SCT. Fourteen patients achieved remission after relapse. Two with CT (2, 2 months), three with SI (3, 19, 19+ months), six with DLI (3, 8, 9, 14, 20, 36 months) and three with second SCT (2, 4, 6 months). Conventional CT was able do re-establish donor hematopoiesis and patients achieving remission showed a significantly better survival than patients with refractory disease. Patients who were brought into remission by DLI or cessation of IS had a significantly better survival than patients who achieved remission with CT alone or a second SCT. We conclude that a selected group of patients achieving remission with regeneration of donor hematopoiesis following CT might benefit from immunotherapy as consolidation.