Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia in Adolescents and Young Adults

Amy Y. Wang, MD, MPH; Lori S. Muffly, MD, MS; Wendy Stock, MD


J Oncol Pract. 2020;16(5):231-238. 

In This Article

Abstract and Introduction


Adolescents and young adults (AYAs) with Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL) represent a unique patient population with a disproportionate survival disadvantage compared with younger children. Substantial progress has been made as we began to understand and address the multifaceted drivers behind this outcome disparity. New insights into the biology of B-cell ALL have uncovered distinct genetic characteristics more commonly found in AYAs that affect prognosis. Dramatic improvements in survival have been achieved with the use of pediatric-inspired protocols in the front-line setting, as well as antibody-based and chimeric antigen receptor T-cell therapies in the relapsed and refractory setting. Guided by the incorporation of minimal residual disease testing to inform clinical decision making, these represent major paradigm shifts in management. Efforts to design clinical trials geared toward AYAs and to enroll AYAs in available clinical trials will ensure ongoing progress. Holistic care of AYAs with ALL further involves recognition of psychosocial issues arising as a consequence of their diagnosis and the delivery of age-appropriate supportive care.


The management of Philadelphia chromosome (Ph)–negative acute lymphoblastic leukemia (ALL) has changed dramatically in recent years. Adolescents and young adults (AYAs) with ALL emerged as a unique patient population when AYAs were recognized to have a disproportionate survival disadvantage as compared with their younger counterparts.[1,2] The National Cancer Institute defines AYA as an individual age 15 to 39 years of age at the time of cancer diagnosis.[3] Not only are incidence rates of acute leukemia increasing in this age group but population-level data available through the US SEER program revealed a sharp decline in 5-year ALL survival rates from 75% at age 17 years to 48% at age 20 years, termed the survival cliff.[4] Hence, there has been substantial interest in understanding the drivers of this survival disparity and in improving their outcomes.