The prognosis of adult patients with ALL remains unsatisfactory. AlloSCT is associated with a beneficial GVL response mediated by donor T cells. However, GVHD results in substantial mortality and long-term morbidity. T-cell depletion (TCD) of the graft reduces the severity of GVHD, but is associated with an increased relapse rate after alloSCT. Therefore, early sequential donor lymphocyte infusion (DLI) is likely to be necessary for a successful GVL reaction. Twenty-five adult ALL patients (10 Ph+ ALL) were eligible for early DLI after initial disease control with myeloablative TCD-alloSCT in first CR (CR1), if active GVHD was absent at 3–6 months after alloSCT. Patients with a sibling donor or an unrelated donor were scheduled for 3.0× 10 6 CD3+ cells/kg or 1.5× 10 6 CD3+ cells/kg, respectively, at 6 months after alloSCT. Three patients died before evaluation (one early relapse). Five patients had active GVHD. Fourteen of the remaining seventeen patients received DLI (median time-to-DLI: 185 days). Overall, only 17% required long-term systemic immunosuppression for GVHD. With a median follow-up after TCD-alloSCT of 50 months, 2-year survival probability was 68%(95% confidence interval (CI) 49–87%). In conclusion, myeloablative TCD-alloSCT with early sequential DLI is an efficient and safe post-remission treatment for adult ALL patients in CR1.