The role of T cell depletion in allogeneic stem cell transplantation for acute myeloid leukemia (AML) remains controversial. This study describes the results of an alemtuzumab-containing myeloablative regimen used to transplant 51 consecutive patients with hematological malignancy. Diagnoses were AML (n=48) of which 8 were secondary (6 transformed MDS; 2 therapy-related AML) or MDS (n= 3). Median age at transplant was 38yrs (range 13–57), and 29 patients had unrelated donors. Sixteen patients were HLA-mismatched at up to 3/10 loci (8x1; 7x2; 1x3). The majority of patients (39/51; 76%) were high-risk for relapse, as defined by induction failure (>15% blasts after one course of induction chemotherapy or >5% blasts after 2 courses), adverse cytogenetics, >CR1, or secondary disease. Six patients (12%) had residual detectable disease at the time of transplant despite at least 3 courses of induction therapy. Patients received cyclophosphamide 120 mg/kg and fractionated total body irradiation (14.4 Gy). Those with unrelated donors also received fludarabine 90 mg/m2. Stem cell source was bone marrow in 11 patients and PBSC in the remaining 40. Stem cells underwent in vitro T cell depletion using 20mg alemtuzumab added to the bag. All patients also received cyclosporin A for GvHD prophylaxis. Median follow-up for the surviving patients is 29 months (range 3–49). The estimated event-free survival is 70% at 1yr and 58% at 3yrs. Acute GvHD grade II occurred in 8% (no grade III–IV) and extensive chronic GvHD in 22%. Non-relapse mortality was 17% at 1yr and 25% at 3yrs, and relapse has occurred in 9 patients, giving an estimated relapse risk of 21% at 3yrs (24% in high-risk patients, n=39). For EFS and NRM, the only significant variable is age >45yrs at transplant, with no significance for donor type or presence of HLA mismatch. For patients aged ≤ 45yrs at transplant (n=42), of whom 81% were high risk for relapse, the outlook is very good with estimated NRM of 15% at 3yrs, and EFS of 69%. Use of this regimen therefore permits the successful transplantation of younger patients with high-risk disease and HLA-matched or mismatched unrelated donors, with minimal acute GvHD, low non-relapse mortality and no evidence of an excessive relapse rate, when compared to regimens without T cell depletion.