Background: Myeloablative hematopoietic cell transplant (HCT) for leukemia/lymphoma is highly toxic and often not well tolerated. Total lymphoid irradiation and antithymocyte globulin (TLI-ATG) is a nonmyeloablative (NMA) stem cell therapy developed at Stanford that protects against GVHD by increasing T-reg proportion. We have incorporated TLI-ATG as our preferred NMA regimen in pts with increased age, poor performance status, or other unfavorable markers. We describe our experience thus far with our first pts treated with TLI-ATG. Methods: Six pts with mantle cell lymphoma, AML or ALL underwent TLI-ATG and allogeneic HCT from 4/2009 to 7/2010. Protocol is in NEJM 2005;353:1321-31. Median age was 63y and median no. of prior chemotherapy cycles was 7.5; 1 pt had prior auto HCT. All pts were in CR prior to TLI-ATG and received HLA matched grafts. GVHD prophylaxis was tacrolimus/cyclosporine with MMF. Chimerism studies were performed and GVHD development, RFS, and OS were assessed. Results: All pts tolerated TLI-ATG well and all but 2 achieved donor lymphocyte chimerism >90% by day +32 (range 92-97.5%). RFS and OS at 100d was 100%. Using Kaplan-Meier analysis, the 1y overall survival rate is 62.5%. Pt 1 relapsed day +613 and responded to salvage therapy. Pt 2 failed to engraft even after 2nd HCT with flu/TBI and DLI. Pts 3 and 5 experienced aGVHD of the skin (grade 1; improved w/steroids) and GI tract, respectively. Pt 4 developed oropharyngeal cGVHD. Pts 2 and 5 developed CMV colitis/esophagitis. Pts 3 and 4 are doing well off immunosuppressants at ~1y post HCT. Pt 6 started to lose his graft ~day +165 but has responded to DLI with increasing donor chimerism. Conclusions: In this heavily pretreated pt population, TLI-ATG was well tolerated. The lack of myeloablative toxicity makes it a reasonable option for pts who may not otherwise be candidates for transplant.