<h3>Purpose/Objective(s)</h3> Stem cell transplantation (SCT) is associated with anemia, thrombocytopenia and other bone marrow dyscrasia in the peri-transplant setting. We previously conducted a phase I clinical trial of patients undergoing SCT after total body irradiation (TBI) (≥ 400 cGy), which showed that eltrombopag (Epag), a thrombopoietin analog was very well tolerated in a cohort of SCT population. Epag is unique in that it has also shown multi-lineage effects of hematopoiesis (platelets, white blood cells [WBC], and red blood cells [RBC]) in patients with severe myelodysplastic syndrome. We compared our cohort of patients with historical data of patients who received standard SCT (without Epag), as well as with pair-matched patients in the historic group. We hypothesized that patients who received TBI and Epag would have reduced need for transfusion of blood products, and reduced platelet and WBC engraftment times. <h3>Materials/Methods</h3> Data in patients undergoing standard SCT (without Epag treatment) from 2005 - 2009 were retrospectively compared to our cohort of patients who received TBI and Epag in a phase I clinical trial. A two-sided t-test was conducted to evaluate the number of platelet and RBC transfusions, as well as platelet and neutrophil engraftment times between the two groups. In addition, pair-matched groups of patients selected from the standard SCT group were compared with the phase I study cohort controlling for variables such as age, sex, and TBI evaluated via two sample-t test to determine difference in transfusions of blood products. <h3>Results</h3> The TBI/Epag cohort from our phase I clinical trial (n=15) was compared to historical SCT cohort in our registry (n= 235) who received SCT (without Epag). Mean total number of platelet transfusions was 4.0 vs. 13.6 units (p < 1.59 × 10^0.6), and mean total RBC transfusion was 5.6 vs. 10 units (p<0.02), respectively. Time to platelet, and WBC engraftments were 15.3 days vs. 26.8 days (p < 6.07 × 10 ^0.05), and 12.1 days vs. 17.4 days (p< 0.01), respectively. The TBI/Epag cohort was compared with matched historical cohort by age (< 40 y/o), sex, and TBI conditioning regimen (n=4, 11, respectively), which showed mean total platelet transfusions of 13 vs. 16.5 units (P < 0.1), and mean RBC transfusions of 4.75 vs. 11.45 units, respectively (p< 0.01). TBI/Epag cohort was also matched to a second older age cohort (60 - 70 y/o), sex, and TBI conditioning (n = 4, 7, respectively). In this group, the mean number of platelet transfusion was 0.5 vs. 10.0 units (p< 0.04), and RBC transfusion was 2.25 vs. 8.29units (p <0.04). <h3>Conclusion</h3> Our data indicates that Eltrombopag markedly reduced the time to platelet engraftment, WBC engraftment, as well as the number of platelet and RBC transfusions, when compared with historical control groups, especially in the older aged cohort.