The evolving art of hematopoietic stem cell transplantation: translational research in post-transplant immune reconstitution and immunosuppression
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Allogeneic hematopoietic stem cell transplantation (SCT) offers the best chance for cure and/or long-term survival for a broad range of diseases, including many high-risk hematologic malignancies, bone marrow failure states and subsets of inherited metabolic diseases and hemoglobinopathies. Clinical advances in allogeneic SCT have resulted in dramatically improved clinical outcomes over the past two decades, resulting in a significant expansion of transplant utilization to many recipients who would previously have been excluded from consideration, including elderly recipients and individuals lacking matched sibling or unrelated donors. Despite these advances, significant clinical challenges remain, including delayed immune reconstitution and the frequent occurrence of acute and chronic graft-versus-host disease, especially in the unrelated donor transplant setting. Translational laboratory efforts, facilitated by technical advances in our ability to measure thymopoiesis and functional T cell subsets in humans, have resulted in an improved understanding of immune recovery and have provided novel insights that may lead to more rational and selective immunosuppression.
KeywordsHematopoietic stem cell transplantation T cell immunology Thymopoiesis Immune reconstitution Immunosuppression
The authors thank Tae Kon Kim (Yale University) and Takero Shindo (Saga University) for their scientific contributions to the work discussed. The authors thank Marcos de Lima, Elizabeth Shpall, Ian McNiece and Richard Champlin (MD Anderson Cancer Center), Paul Szabolcs and Joanne Kurtzberg (Duke) for their collaborative clinical and laboratory efforts. This work was supported, in part by the generous funding from the National Institutes of Health (NCI RO1 CA109326 to K. V. K. and NHLBI RO1 HL091749 to K. V. K. and Paul Szabolcs) and the Kalish Family Foundation (to K. V. K.).
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