BACKGROUND AND OBJECTIVES: The outcome of adult patients with acute lymphoblastic leukemia (ALL) is discouraging, only about 30% of them becoming long-term survivors. A small fraction of patients are resistant to the first line treatment, while most patients relapse within two years of achieving complete remission (CR). No standard treatment exists for refractory or relapsed patients. The GIMEMA group designed a phase II trial for adult ALL patients with refractory or relapsed disease. DESIGN AND METHODS: Patients aged >15 years with primary refractory or relapsed ALL were eligible for this study. The salvage strategy included a single high dose of idarubicin combined with high dose cytarabine, followed by consolidation therapy leading to a stem cell transplant procedure according to donor availability. RESULTS: From 1998 to 2002, 135 patients were enrolled. Seventy-five patients (55%) achieved CR, including 12 Philadelphia-positive cases; 44 patients had persistent leukemia and 16 died during reinduction. Fifty patients received a stem cell transplant: 19 from an HL-A identical sibling, 16 from an unrelated donor, 7 from a haploidentical relative, 2 received cord blood, and 6 had an autotransplant. The median disease-free and overall survival were both short (5.0 and 6.4 months, respectively); however, after a median follow-up of 40 months, 13 patients are alive, 10 of whom are free of disease (9 transplanted), while 3 are alive with leukemia. Interpretation and CONCLUSIONS: The treatment induced CR in a high percentage of poor prognosis patients, thus rendering a transplant procedure feasible in most of them. However, significant rates of transplant-related mortality and post-transplant relapse encourage the search for more effective and less toxic conditioning regimens.