Graft versus Leukemia effects due to alloreactive NK-cells after HLA mismatched stem cell transplantation in children with refractory leukemia

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We investigated HLA expression on leukemic cells derived from patients at diagnosis and relapse after hematopoietic stem cell transplantation (HSCT) using flow cytometry with locus-specific antibodies. Some relapsed patients demonstrated loss of HLA alleles in leukemic cells at relapse. Single-nucleotide polymorphism array analyses revealed acquired uniparental disomy on the short arm of chromosome 6, resulting in the total loss of the mismatched HLA haplotype. We also found that primary leukemic blasts in this patient were not killed by the donor NK cells, however, leukemic blasts at relapse were efficiently killed after HLA loss of leukemic cells occurred. These results suggested that the escape from immunosurveillance by the loss of mismatched HLA alleles may be a crucial mechanism of relapse after HLA-haploidentical HSCT. These findings may give us the rationale of donor NK cell infusions in suitable setting after HLA haploidentical HSCT to prevent relapse.