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KEY CONCEPTS

  • Allogeneic stem cell transplantation (allo-SCT) remains the only curative intervention for a variety of high-risk hematologic malignancies. Haploidentical grafts from a first-degree related mismatched donor extends the applicability of this lifesaving treatment to a large proportion of patients who otherwise do not have a suitable human leukocyte antigen–matched donor.

  • Breakthrough advances achieved over past decade in controlling the bidirectional alloreactivity and in graft engineering have led to a decreased incidence of complications, including graft-versus-host disease and nonrelapse mortality (NRM), without compromising the graft-versus-tumor effect.

  • The use of haploidentical transplantation continues to increase with growing evidence for its effectiveness in several myeloid and lymphoid neoplasms. Haploidentical use has taken precedence compared with some other alternative donor sources given its immediate availability and cost-effectiveness.

  • Fully matched related donors remain the preferred graft source for allo-SCT. However, several transplant registry studies in United States and Europe have confirmed comparable survival outcomes between matched unrelated and haploidentical transplants.

  • The results of the large phase 3 randomized Bone and Marrow Transplant Clinical Trials Network multicenter clinical trials were reported recently confirming superiority of haploidentical transplant over double cord transplant in terms of improved overall survival and decreased NRM.

  • Several factors are considered when choosing the best haploidentical donor. The donor-specific antibodies remain one of the most important factors to consider because the presence of antibodies is associated with a high risk of graft failure. Younger donors, male donors, fathers rather than mothers, and first-degree to second-degree donors are preferred graft sources for recipients of haploidentical transplants.

INTRODUCTION

Haploidentical stem cell transplantation (HaploSCT) from a first-degree related mismatched haplotype donor (siblings, children, parents) extends the application of this lifesaving treatment to a large proportion of patients with high-risk hematologic malignancies who otherwise do not have a suitable human leukocyte antigen (HLA)–matched donor.1 As the average family size continues to shrink, the likelihood of finding an HLA-matched related sibling donors continues to decrease.2 Moreover, with aging of the United States population, finding a young healthy sibling donor becomes increasingly less likely. The use of matched unrelated donors (MUDs) is limited by a longer time to transplantation (median, 3–4 months), which makes it difficult to treat patients with more advanced disease in rapid need for a transplant. The ethnicity or race of the recipient can have great impact as well in identifying a suitable MUD because approximately 30%, 70%, and 90% of the white, Hispanic, and African American population do not have a MUD in the worldwide registries.3 In contrast to unrelated donor grafts, haploidentical (or “half-matched”) donors can be immediately available, and there are no costs associated with an unrelated donor search, graft acquisition, maintaining a registry, or coordinating logistics with distant donor centers. This is an especially valuable option for nonwhite and mixed-race individuals who frequently have no available matched donors to proceed with transplantation.3 This approach might also be particularly useful in developing countries that may not have ...

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