Defining the Role of Donor Lymphocyte Infusion in High-Risk Hematologic Malignancies

The infusion of lymphocytes from the original donor (DLI) to a recipient of an allogeneic stem cell transplantation (SCT) has been the case of cellular immunotherapy. Following its introduction in the late 1980's, unmodified donor cells have been used within the treatment of post-transplant relapse in various hematological malignancies. Later on, preemptive and prophylactic strategies were introduced. Over time, clinical experience identified both the therapeutic potential and the limits of this strategy, prompting numbers of different approaches to improve efficacy and safety of unmodified DLI. Among these were activation of cell subsets by cytokines or growth factors, selection and expansion of specific T-cell subsets, and infusion of NK-cells. Later on, genetical T-cells engineering, including suicide gene technology, T-cell receptor gene transfer and most recently the CAR T-cells, entered the field to increase the allogeneic Graft-versus-Malignancy effect while reducing the risk of complications such as Graft-versus-Host disease. Similarly, synergistic effects of DLI with pharmacological approaches were discovered, leading to combined strategies. Nevertheless, standardization of the "drug" DLI and its clinical use is still challenging, and many sophisticated modifications of DLI still have to prove their suitability for a broader use. Further, increasing knowledge on escape mechanism from an allogeneic immune reaction need to be considered for the clinical application of DLI. Hence, further research requires intelligent strategies and international cooperation to fully exploit the potential of adoptive cellular immunotherapy in the context of allogeneic SCT.