Cellular therapies in acute lymphoblastic leukemia.
Review
Overview
abstract
ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die of their disease, whereas in the pediatric setting, relapsed and refractory disease remains a therapeutic challenge. Cellular therapy through allo-HSCT remains an option for these patients, and recent advances in alternative forms of allo-HSCT, including unrelated donor transplants, UCB transplants, and haploidentical transplants, have expanded the numbers of patients eligible for allo-HSCT but have not improved outcomes when compared with HLA-matched related allo-HSCTs. In light of this persistent failure, several novel adoptive cellular approaches are being investigated to treat patients with ALL. The use of enriched WT-1–specific donor T cells to treat patients with ALL is currently under investigation in phase I trials at several centers. Treatment of ALL with genetically modified T cells targeted to the CD19 antigen through the expression of a CD19-specific CAR also have entered phase I clinical trials at several centers. Similarly, a clinical trial treating patients with ALL with genetically modified NK cells targeted to the CD19 antigen has recently opened for accrual. Collectively, these ongoing and anticipated trials provide a promising role for adoptive cellular therapies in the treatment of ALL. What remains to be seen is whether this promise will either translate into improved outcomes for these patients or provide significant insights on which to design second-generation adoptive cell therapeutic clinical trials for ALL in the future.
