Relapsed acute lymphoblastic leukemia (ALL) with high minimal residual disease (MRD) after reinduction has poor prognosis. ALL patients with Down syndrome (DS) have a higher rate of relapse and treatment related mortality. We describe a DS and ALL patient with late bone marrow relapse who was treated per British ALL R3 reinduction chemotherapy. His therapy was discontinued due to severe systemic infections. The patient remained in remission for approximately two years without further treatment. We hypothesize that the sustained remission is attributed to chemotherapy combined with increased cortisol production and cytokine release as a result of systemic stress from infections.