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Contamination of reinfused stem cells with leukemic cells is a major concern affecting outcomes after ASCT in patients with CLL. In fact, outcomes after ASCT strongly correlate with disease status before transplantation. Persistence of minimal residual disease (MRD), as detected by consensus primer PCR, or the switch from a negative to a positive MRD status during follow-up, are both highly predictive of clinical relapse after ASCT. In order to minimize the risk of contaminating the collection with leukemic cells, in our institution patients who undergo an ASCT receive alemtuzumab before peripheral blood stem cell (PBSC) mobilization, to purge in vivo any residual disease. We evaluated the outcome of ASCT in 20 CLL patients who were pretreated with fludarabine (FAMP) containing regimens and subsequently received alemtuzumab SC (10 mg x 3/w for 6 weeks) to purge MRD. A FAMP containing regimen had been administered as first-line treatment in 18 cases and as second-line in 2 cases; median number of FAMP cycles administered was 6 (range, 4–8). All but 1 PBSC patient was mobilized with Ara-C (800mg/m2/12h x 3 d) followed by G-CSF, while the last patient received only G-CSF. Median age at transplant was 56 y (range, 45–65); all patients (pts)were in CR based on the NCI-WG criteria. Of 20 pts who underwent PBSC harvest, polyclonal IgH rearrangement was evident in 13 pts (65%), as assessed by PCR. The conditioning regimen consisted of 12 Gy TBI plus cyclophosphamide 120 mg/kg in 14 pts < 60 yrs, and Melphalan 180 mg/sqm in 6 pts >60 years. Median number of CD34+ cells reinfused was 17.4 x106/kg (range, 3.1–30.4), and in 13 cases the reinfused product was polyclonal for IgH. The median time for PMN (>500/ml) and PLT (>20000/ml) recovery was 9 (range, 8–11) and 11 (range, 9–13) days respectively. During marrow aplasia 13 patients experienced an episode of fever >38°C with a median duration of 2 days (1–8); in 3 pts the fever was of unknown origin, in 8 cases sepsis was due to Staphilococcus epidermidis,and in 1 case it was due to P. aeruginosa. Intravenous antibiotics were administered in 11 cases, and only 1 patient required intravenous antifungal therapy. One patient died due to a pulmonary fungal infection sustained by Aspergillus Terreus. No incidence of grade 3–4 nonhematologic toxicity was observed. During the 3 months post-transplant 2 pts required hospitalization: 1 for a fever, and the other for acute polyneuropathy. No pathogens were isolated in either case. At 11 months post-transplant 1 patient developed thrombocytopenia. None of the pts developed CMV reactivation, even in the 9 cases, which became CMV positive during alemtuzumab treatment. Herpes Zoster was observed in 2 patients at 5 and 10 months after transplant. At a median of 28 months after receiving alemtuzumab (range, 15–48 months), and a median 17 months after PBSC transplantation (range, 1–41 months), 19 pts are in CR. At the 9- and 12-month post-transplant evaluation, performed on 16 and 12 pts respectively, all but 1 patient showed polyclonal IgH rearrangement. ASCT after sequential treatment with FAMP and Campath-1H is feasible with no significant increase in major infections; a substantial number of patients achieved a sustained polyclonal IgH rearrangement after transplant.