Rationale for using an alternative donor for second allogeneic transplantation. The patient’s 2 HLA haplotypes are shown in blue and red. The first donor shares a common blue haplotype with the recipient and a distinct yellow haplotype. At relapse, the leukemic blasts lose the mismatched red haplotype, which results in loss of cell surface expression of that mismatched HLA molecule. After relapse and subsequent chemotherapy to induce a remission, a second haploidentical donor is selected because they share the red haplotype with the patient, but lack the blue haplotype. This will allow the second donor’s immune system to recognize these disparate HLA molecules on the leukemic blasts to potentially elicit graft-versus-leukemic effects. Figure concept was influenced by two prior publications.^8,73