Stem Cell Transplant As an Immunomodulatory Tool for Children with Hematologic Malignancies

Abstract

Allogeneic stem cell transplantation (alloHSCT) is the most common and effective form of immunotherapy used for treatment of pediatric leukemias. A combination of graft manipulation, donor selection, fine-tuning of conditioning regimens, and use of lower and novel forms of immunosuppression following transplant has maximized the tolerability of alloHSCT in children. This outcome has facilitated new advances in disease-specific transplant regimens that seek to amplify the antitumor effects of the allograft, while reducing transplant-related mortality. However, disease relapse remains the preeminent challenge to the success of transplantation as a modality for successful treatment of high-risk disease. Separating graft versus host disease (GVHD) from graft versus leukemia (GVL) remains the most significant obstacle to enhancing disease-free survival. However, with increased clarity and discrimination in the effector mechanisms responsible for GVHD and/or GVL in patients of all ages, a new wave of clinical trials has become feasible that harnesses GVL effects to treat patients with high-risk myeloid and lymphoid malignancies. Exciting progress is being made in the use of alloHSCT with donor lymphocyte infusions (DLIs) in almost all forms of pediatric hematologic malignancies. This advance sets the stage for the use of HSCT and/or DLI in conjunction with novel disease-specific post-transplant therapies using small molecule therapeutics, tumor vaccines, and novel antibody therapies.