Alternative donor hematopoietic stem cell transplantation: current concepts

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Abstract

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many diseases such as hematological malignancies, bone marrow failure, immunodeficiency and other disorders. Unrelated donor and haploidentical family member are important alternative donors for the patients who need HSCT for otherwise incurable disease but without identical sibling donor. Since the first unrelated HSCT in 1974, the number and the clinical outcomes of unrelated transplant have been progressed significantly over time. More than 16 million adult unrelated donors have been registered worldwide. Near half of the donations from unrelated donors are international in recent years. HLA disparity between donor and recipient and disease status before transplant are key factors on survival after unrelated HSCT. In experienced centers, unrelated transplant has achieved comparable results with identical sibling HSCT. In addition, transplant from unrelated donor has advantage to cure some inherited disorders such as severe combined immunodeficiency disease, thalassaemia, Fanconi anemia, Familial Hemophagocytic Lymphohistiocytosis and so on. Haploidentical HSCT (haplo-HSCT) was initiated in 1981. The early results were poor mainly due to severe graft-versus-host disease (GVHD) and infections post-transplant. To reduce GVHD, T-cell depletion and mega dose CD34 + cells have been employed with certain success. Reduced intensity conditioning has further decreased early transplant-related mortality (TRM), but relapse rate is relatively high. Haplo-HSCT in our group with GIAC regimen has achieved comparable outcomes in terms of severe acute GVHD, chronic GVHD, relapse, TRM, disease-free survival (DFS), and overall survival (OS) with HLA-identical sibling transplant. New strategies have been applied in order to better manage complications post HSCT. As the third party cells, cord blood co-infusion has reduced severe acute GVHD and early TRM significantly. The majority of refractory cytomegalovirus, Epstein–Barr virus and aspergillus infections can be controlled with adoptive cellular therapy. Our clinical results from a large series of transplants have demonstrated that haplo-HSCT in sex-matched donor–recipient pair has survival advantage. Early disease stage before HSCT and high CD34 + cell infused but not age and HLA disparity have positive influence on DFS and OS. Therefore, it is better to consider haplo-HSCT for the patients who need urgent transplant to cure the diseases at earlier disease stage, when matched siblings or unrelated donors are not available. Among all haploidentical family members, sex-matched one should be the first choice as a donor for HSCT.

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