The feasibility of nonmyeloablative stem cell transplantation (NST) was evaluated in 22 adults with high-risk ALL. 16/22 patients had advanced disease and 11/22 had Ph+ ALL. Eleven patients received NST as first stem cell transplantation (SCT). Eleven patients had relapses after allogeneic or autologous SCT and underwent a salvage NST. 18/22 patients (82%) engrafted after NST. 13/16 patients (81%) with active disease reached complete remission (CR). 11 of 13 patients developed GVHD. After first NST 10/11 patients (91%) engrafted. Six of seven patients with active disease reached CR. Three of five relapsing patients reached subsequent CR after donor lymphocyte infusions, termination of immunosuppression or imatinib. Three of 11 patients (27%) are alive in CR 5 to 30 months after NST. Eight of 11 patients have died, 3/8 from leukemia and 5/8 from transplant-related causes. After salvage NST, 8/11 patients (73%) engrafted. Seven of nine patients with active disease reached CR. Only one of 11 patients transplanted, who was in CR before undergoing salvage NST is alive 19 months after NST. Five of 11 have died from leukemia, one of 11 after graft failure and four of 11 from transplant-related causes. Four of 22 patients (18%) are alive in CR 5, 14, 19 and 30 months after NST. NST is feasible in adults with high risk ALL. However, transplant-related mortality remains high and only patients transplanted in CR seem to have long-term disease-free survival.