The current landscape: Allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia

One of the consistent features in development of hematopoietic stem cell transplant (HCT) for Acute Lymphoblastic Leukemia (ALL) is the rapidity with which discoveries in the laboratory are translated into innovations in clinical care. Just a few years after murine studies demonstrated that rescue from radiation induced marrow failure is mediated by cellular not humoral factors, E. Donnall Thomas reported on the transfer of bone marrow cells into irradiated leukemia patients. This was followed quickly by the first descriptions of Graft versus Leukemia (GvL) effect and Graft versus Host Disease (GvHD). Despite the pivotal nature of these findings, early human transplants were uniformly unsuccessful and identified the challenges that continue to thwart transplanters today - leukemic relapse, regimen related toxicity, and GvHD. While originally only an option for young, fit patients with a matched family donor, expansion of the donor pool to include unrelated donors, umbilical cord blood units, and more recently the growing use of haploidentical donors have all made transplant a more accessible therapy for patients with ALL. Novel agents for conditioning, prevention and treatment of GvHD have improved outcomes and investigators continue to develop novel treatment strategies that balance regimen related toxicity with disease control. Our evolving understanding of how to prevent and treat GvHD and how to prevent relapse are incorporated into novel clinical trials that are expected to further improve outcomes. Here we review current considerations and future directions for both adult and pediatric patients undergoing HCT for ALL, including indication for transplant, donor selection, cytoreductive regimens, and outcomes.