6519 Background: Allogeneic transplantation from a haploidentical family donor (haplo-SCT) represents the ideal solution to offer to every and each patient with high risk leukemia the potential cure of allogeneic adoptive immunotherapy. However, the delayed immune reconstitution compromise haplo-SCT with a high rate of late mortality and relapse. Methods: In a phase II multicenter trial (MM TK007), we explored early add-backs of donor lymphocytes genetically engineered to express the herpes simplex thymidine kinase (TK-DLI) suicide gene after haplo-SCT, in inducing early immune reconstitution and selective control of GvHD by ganciclovir. Results: Thirty-one advanced age pts (median age 51, 17–64) were transplanted for high risk leukemia. No immune reconstitution and no graft versus host disease (GvHD) were observed in absence of TK-DLI. 17 pts received TK-DLI at a median dose of 107/kg with 1st infusion at d +42; 14 pts obtained a prompt and sustained immune reconstitution with CD3+ >100/mcl at a median time of 86 d (57–127) from SCT and 21 d (13–42) from TK-DLI. Six pts developed acute (GvHD), (grade I to IV) that was always completely abrogated by ganciclovir. In patients in remission of leukemia at time of SCT, who were alive at day +42 and received TK-DLI, overall survival was 65% at 2 years (intention-to-treat analysis: 46%).The cumulative incidence of TRM and relapse showed a 40% probability of mortality with a median time of death of 90 days and last event at day +166. The cumulative infectious mortality beyond day 100 post transplant was 12.5% in our population, versus 53% of historical data. These data correlate with rapid development of normalization of the T cell repertoire documented by spectratype, followed by detection of high frequencies of T cells specific for CMV and EBV by gIFN ELISpot. Conclusions: These results indicate that TK-DLI drastically reduces late mortality after CD34+ haplo-SCT in adults. Survival rates in patients treated with TK-DLI were superior to survivals of haploidentical SCT of EBMT registry database. A phase III randomized multicentric study will start in 2006 to validate prospectively the advantage of TK-DLI in haplo-SCT. [Table: see text]