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Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy for a variety of malignancies, including leukemias, lymphomas, and myeloma. Several complications limit its use including relapse of malignancy, graft versus host disease, and prolonged immune depletion caused by the conditioning required for successful transplantation – all of which can lead to increased morbidity and mortality after allo-HSCT. My laboratory uses murine HSCT models to study clinically important problems in HSCT and to test novel therapeutic strategies which can be translated into clinical practice.