Down syndrome (DS) is one of the most common chromosomal disorders and the children with are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). These patients also face lower survival rates due to unique biological features of the leukemic blasts and substantially increased therapy related mortality. Blinatumomab has been shown to be safe and effective having excellent results and in patients with relapsed/refractory (R/R) BP-ALL. We report here use of blinatumomab, a bispecific T-cell engager antibody construct, in 3 patient with DS and relapsed/refractory BP-ALL . ALL patient had no significant toxicity and achieved remission after only one cycle of blinatumomab .