Addition of Clofarabine to TLI/ATG Conditioning: Impact on Immune Reconstitution and Clinical Outcomes,

Abstract 4066 The fundamental challenge in designing an effective conditioning regimen for allogeneic transplantation involves the prevention of disease relapse while minimizing the risk for Graft versus Host Disease (GVHD). Treatment with total lymphocyte irradiation (TLI) and anti-thymocyte globulin (ATG) has been shown to minimize the risk of GVHD through the biasing of the T cell reconstitution towards an inhibitory phenotype. However, disease relapse remains a significant concern. Clofarabine is a second generation nucleoside analog with potent cytoreductive capacity and demonstrates efficacy in hematological malignancies. In this study, we examined the combination of clofarabine, TLI and ATG with respect to T cell reconstitution, risk for GVHD and transplant outcome. Sequential cohorts of 5 patients were treated with TLI and ATG alone or in conjunction with 20 mg/m 2 , 30 mg/m 2 or 40 mg/m 2 of clofarabine for 5 days. Cyclosporine and mycophenolate mofetil were administered as GVHD prophylaxis. Twenty patients have been enrolled (5 AML/MDS, 2 ALL, 6 lymphoma, 2 CLL, 5 myeloma) and received HLA matched peripheral blood stem cells collected from related (N=11) and unrelated donors (N=9). Of 19 evaluable patients, 15 are alive with a median follow up of 665 days. Day 30 and 100 mortality was 0% for TLI and ATG and 0% and 10% for those receiving clofarabine. The maximum tolerated dose (MTD) of clofarabine was 30 mg/m 2 as 2 patients experienced treatment related mortality at the 40 mg/m 2 dose level. Grade 5 infections and multiorgan failure occurred in both patients. All patients demonstrated engraftment with mean bone marrow donor chimerism of 92.5% at Day 30. The first cohort9s ANC did not drop below 500 cells/uL, while median time to neutrophil engraftment in the patients who received clofarabine was 9 days. The median time to platelet recovery was 11 and 12 days for patients receiving TLI and ATG alone or with clofarabine, respectively (p=0.39). T cell reconstitution studies demonstrated a significant decrease in CD4+ cells to ( Disclosures: Chen: Genzyme: Membership on an entity9s Board of Directors or advisory committees. Avigan: Genzyme: Research Funding.