Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

Abstract

Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.

Persistent donor derived Vδ4 T cell clones may improve survival for recurrent T cell acute lymphoblastic leukemia after HSCT and DLI

“…Even after undergoing RE3, the OS time of the patient was much longer than expected. The long-term disease remission of this patient and serial DLI treatment after achieving a third CR with persistent cGvHD were signals reflecting that an immune response was mediated by the grafts or the infusion of cells from the donor [12, 13]. However, as we knew, there were also examples that DLI was failed to rescure patients with relapse leukemia after HSCT.…”

Preservation of cell-based immunotherapies for clinical trials

“…Hematopoietic stem cell transplantation (HSCT) has been implemented successfully for the treatment of hematologic malignancies since the late 1950s [14]. However, the incidence of graft-versus-host disease (GVHD) following allogeneic stem cell transplantation is associated with various adverse effects in patients and results in a decrease in survival.…”

Multistate modeling and simulation of patient trajectories after allogeneic hematopoietic stem cell transplantation to inform drug development

“…The pioneering first allogeneic HSCT was performed in 1957 (Thomas, Lochte, Lu, & Ferrebee, 1957), following years of basic research that stood under the impression of World War II and the use of the atomic bomb, which had led researchers to search for ways of restoring damaged bone marrow function (Henig & Zuckerman, 2014). Autologous HSCT is the transplantation of the patient's own stem cells and allows the rapid restitution of bone marrow function after administration of high-dose chemotherapy.…”