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7003 Background: Haploidentical family donors represent the ideal solution to offer for every patient with high risk leukemia the potential cure of hematopoietic stem cell transplantation. Extensiv...

7007 Background: Suicide gene therapy (SGT) was firstly applied to allogeneic HSCT, addressing the need for modulation of graft vs host disease (GvHD) reactions while preserving graft vs leukemia (GvL) effect of alloreactive T cells. HSV-TK gene insertion in donor T-cells modulates alloreactivity by selectively destroying dividing alloreactive cells involved in GvHD. Methods: Long-term safety and survival was assessed in 128 pts entering worldwide 10 phase I-II trials that used TK-DLI to improve GvL, immune reconstitution (IR) and GvHD control. In all, 57 pts received TK DLI at our Institution: 23 to treat relapse after HLA-identical HSCT (Ciceri, 2007) and 34 to improve IR after haploidentical HSCT (Ciceri, Bonini, 2009). Results: SGT was feasible, safe and effective in promoting a dynamic and specific modulation of alloreactivity. TK-DLI clinical benefit, defined by chimerism, tumor response and/or IR, was achieved by 65 pts (51%). Grade 2 to 4 GvHD (n=28, 22%) was fully controlled by SGT. TK-DLI engrafted in 51 pts (90%) and, being detectable at low frequency up to 14 yrs, no SGT-related adverse events occurred. In HLA-identical setting (n=23; median follow-up, 15 yrs), 11 pts (48%) had disease response and 2 pts (9%) were alive in complete response (CR). In haploidentical setting (n=34; median follow-up, 7 yrs), 25 pts (73%) had IR and 9 pts (26%) were alive in CR. All pts were monitored according to guidelines on long-term survivors (Majhail, 2012). There were no major infections, while 3 pts had a second tumor. Immunity against TK-DLI was reported exclusively after HLA-identical allo-HSCT indicating that TK-DLI is not limited by SGT-specific immunity after haploidentical HSCT. Conclusions: Long-term follow-up confirms the high benefit to risk ratio of TK-DLI. A phase III trial is ongoing in haploidentical HSCT (NCT00914628). Clinical trial information: NCT00423124.

6534 Background: Hematopoietic Cell Transplantation from partially-HLA matched family donors (haplo-HCT) represents a promising therapy for high-risk leukemia. The infusion of donor lymphocytes tra...

6515 Background: Haplo-identical stem cell transplantation (haplo-SCT) is a therapeutic option for patients with high risk hematologic malignancies lacking an HLA matched donor. The full exploitation of haplo-SCT is limited by delayed immune recovery, resulting in prolonged risk of life-threatening infections. Infusion of small numbers of donor T cells, aimed at providing immune reconstitution, results in severe forms of graft-versus-host-disease (GvHD). We previously showed that infusion of donor lymphocytes (DLI) expressing the herpes simplex virus thymidine kinase (Tk) is an efficient tool for controlling GvHD and preserving anti-tumor activity. Methods: We designed a dose-finding clinical protocol of Tk-DLI for immune reconstitution and relapse prevention after haplo-SCT. Eight pts with high risk hematologic malignancies who underwent haplo-SCT received escalating doses (10e6–10e7/kg) of Tk-DLI from day +42. Results: Transduced cells were documented ex vivo in all evaluable pts. While no CD3+ cells we...