Abstract: There is a general debate about the treatment strategy of Ph negative adolescent and young adult acute lymphoblastic leukemia. Clinical researches show the patients in the standard risk group can benefit from the pediatric-inspired protocol. Several reasons may contribute to the superiority of the pediatric inspired protocol to the adult protocol, including the genetic characteristics of these patients, using non-myelosuppression agents, higher dose of Methotrexate, and more intensive CNS for prophylaxis and treatment. Patients in the high risk group can benefit from the Allo-HSCT. Furthermore, MEF2D fusion gene and Ph-like ALL are shown to be the risk factors for poor prognosis. In this article, we will review the research advances of the prognosis and treatment strategy of this disease.