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Abstract
Much of the success of hematopoietic stem cell transplantation (HSCT) has been due to the ability to overcome posttransplant complications, by performing HLA genotypically matched or even mismatched sibling donor HSCT or unrelated donor HSCT. Based on the promising results with using vigorously T-cell-depleted high-dose peripheral blood stem cell transplants by the Perugia University group, several methods to eradicate refractory leukemic cells have been employed worldwide. However, there are limitations of the existing data regarding haploidentical HSCT, that is, the small numbers of patients and the heterogeneous patient populations in most of the published series. Also, researchers have not exactly demonstrated the effect of natural killer (NK) cell alloreactivity in various settings of allogeneic HSCT. In reality, haploidentical HSCT is possible without T-cell depletion. However, it isn’t clear whether reduced-intensity HSCT from a haploidentical related donor or a mismatched unrelated donor is feasible. Anyhow, successfully overcoming the major histocompatibility barriers with using related or unrelated donors means that virtually all patients would have an immediately available donor for desperately needed HSCT. The full potential of haploidentical HSCT may be ultimately achieved through a better understanding of the transplant immunology, including the Korean specificity of killer cell immunoglobulin-like receptor polymorphism. Further study and better support from Korean government insurance coverage that would offer HSCT to more patients in need of transplant and cultivating an optimal NK alloreaction without detrimental complications is urgently required.
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Fig. 3
Comparison of international reports after HLA mismatched donor hematopoietic stem cell transplantation. (A) Overall survival using HLA matched sibling, 1-locus mismatched sibling, and HLA matched unrelated donors in Japan.50) (B) Probability of event-free survival in patients with acute leukemia, either in remission or in relapse from Perugia university, Italy.51) (C) Probability of survival in recipients of matched unrelated (dotted line), mismatched unrelated (dashed line), and haploidentical (solid line) marrow grafts from USA.52) (D) Probability of overall survival HLA-identical or -mismatched related transplantation for patients diagnosed with advanced disease in China.55)
Table 1.
Donor versus recipient natural killer cell alloreactivity in HLA mismatched transplants is determined by the presence or absence of disparity between HLA class I alleles and specific killer cell immunoglobulin-like receptors (KIR). For example, donor natural killer cell expresses KIR 2DL1 and is blocked by HLA-C group 2 alleles, -Cw2 on donor cells and -Cw4 on recipient cells, as shown in the Fig. 1.32)
Table 2.
Different methods of HLA-mismatched related donor hematopoietic stem cell transplantation
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