Abstract
Allogeneic hematopoietic cell transplantation has developed from the years as a last resort into a routine procedure that cures many nonmalignant and neoplastic hematology disorders. Major progress was made in conditioning regimens, prevention of graft-versus-host disease, and diagnosis and treatment of infectious complications. The greatest step forward was arguably the use of an alternative source of hematopoietic CD34+ cells, i.e., HLA-matched unrelated donors, cord blood transplants, and HLA-haploidentical transplants. The obvious advantage of HLA-haploidentical transplant is prompt donor availability of one or more family members. The best donor can be selected on the basis of age, cytomegalovirus status, and natural killer cell alloreactivity. If a patient rejects the graft, a second transplant from the same donor or another donor within the family circle is immediately feasible, and, if the patient needs donor-derived cellular therapies, they are easily accessed. Pioneering studies by Reisner and coworkers showed that full-donor engraftment without graft-versus-host disease was achieved by escalating doses of CD34+ cells in T-cell-depleted bone marrow in mouse models for T-cell-mediated bone marrow allograft rejection. These results provided the biological basis for overcoming the HLA barrier in clinical transplantation. In this chapter we describe the journey of HLA-haploidentical transplantation including challenges and controversies around T-cell-depleted and T-cell-replete forms of grafts.
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Acknowledgment
We thank Dr Geraldine Anne Boyd, lecturer in English, University of Perugia, for assistance in preparing this article. This work was supported by funding from Associazione Umbra Leucemie e Linfomi (AULL), Perugia, Italy.
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Martelli, M.F., Reisner, Y., Champlin, R.E. (2018). Historical Perspective and Current Trends in Haploidentical Transplantation. In: Ciurea, S., Handgretinger, R. (eds) Haploidentical Transplantation. Advances and Controversies in Hematopoietic Transplantation and Cell Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-54310-9_1
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