In the BFM Relapse Study registry we retrospectively identified 136 patients with a first marrow relapse who had undergone BMT in second complete remission (CR2) (group A) and 33 patients who received transplants only after a 2nd bone marrow (BM) relapse had occurred (group B). Event-free survival (EFS) rates at 6 years after BMT were 0.49 +/- 0.05 and 0.48 +/- 0.09 for patients transplanted in CR2 and CR3, respectively. In context with the BFM chemotherapy trials for relapsed childhood ALL there is a clear benefit from BMT in 2nd CR for children with unfavorable prognostic features (isolated early BM relapse, very early BM relapse or BM relapse of T cell ALL). Similar control of leukemia can be achieved with either chemotherapy or BMT in late BM relapse of ALL. Assuming a 60% failure rate with chemotherapy for patients in second relapse, a third remission can be achieved in about 60% of patients who have received chemotherapy, rendering them eligible for BMT in 3rd CR. With this strategy 58% of these patients would survive and late sequelae of BMT be restricted to a minority. To withhold BMT in CR2 and not perform BMT before a 2nd BM relapse has occurred, may be a conceivable alternative for children with late ALL BM relapse, at least if no related donor is available.