In this review, we discuss the current science of HSCT from a historical perspective, highlighting major discoveries. Recent developments in the field of cellular therapy are expected to further improve the efficacy of transplant. However, significant barriers still remain in the form of disease relapse, GVHD infectious complications, and regimen-related toxicities. The development of unrelated donor registries and increased utilization of cord blood and partially matched related donor transplants have ensured a donor for essentially everyone who needs a transplant. Improved donor selection, tailored conditioning regimens, and better supportive care have helped reduce transplant-related morbidity and mortality and expanded access. Preclinical and clinical research in the field has contributed to an advanced understanding of histocompatibility, graft-versus-host disease (GVHD), GVL effect, and immune reconstitution after transplant. Additionally, HSCT has been a curative therapy for several nonmalignant hematologic disorders through the provision of donor-derived hematopoiesis and immunity. The success of transplant for hematologic malignancies derives both from the ability to treat patients with intensive chemoradiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by donor immunity. It has also pioneered the concepts of stem cell therapy and immunotherapy as a tool against cancer. The field of hematopoietic stem cell transplant (HSCT) has made ground-breaking progress in the treatment of many malignant and nonmalignant conditions.
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