Cellular therapies in acute lymphoblastic leukemia.

Overview

The majority of adult patients with acute lymphoblastic leukemia (ALL) will die from the disease. Although the prognosis for pediatric patients is significantly better than for adult patients with ALL, the prognosis for patients with relapsed or refractory disease is poor in all cases. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a related donor offers a significant therapeutic benefit for pediatric patients, although the benefit of this therapy to adults with ALL is less established. Because most patients lack a suitable related donor, alternative approaches to allo-HSCT, including umbilical cord blood, and unrelated and haploidentical allo-HSCT, have been investigated in the clinical setting. Although treatment with donor-derived T-cells, so-called 'donor lymphocyte infusion', has demonstrated poor outcomes in patients with relapsed ALL following HSCT, modified adoptive T-cell regimens, including the infusion of enriched tumor-targeted donor T-cells and genetically targeted T-cells, are currently under clinical investigation. In addition, the resistance of ALL tumor cell lines to NK-cell-mediated lysis may be overcome by the genetic modification of NK cells to target ALL tumor cell antigens, and this approach will be evaluated in an upcoming clinical trial. Whether these novel adoptive cell therapies will ultimately result in improved clinical outcomes remains to be determined.