Clinical experience with full haplotype-mismatched stem cell transplants has a 20-year history. Early results in leukemia patients were disappointing because of a high incidence of severe graft-versus-host disease (GvHD) in T-replete transplants or high rejection rates in T-cell-depleted transplants. The breakthrough came with introduction of a megadose T-cell-depleted progenitor cell transplant following a high-intensity conditioning regimen and the realization that donor natural killer (NK) cell alloreactivity also plays a role in facilitating engraftment and in preventing relapse. Treating end-stage patients inevitably confounded clinical outcome in early pilot studies. Today, high-risk acute leukemia patients are treated at less advanced stages of disease, receive a reasonably well-tolerated conditioning regimen, and benefit from advances in post-transplant immunological reconstitution. These factors have markedly reduced transplant-related mortality. Overall, event-free survival (EFS) and transplant-related mortality (TRM) compare favorably with reports from unrelated matched transplants. T-cell-depleted megadose stem cell transplant from a mismatched family member, who is immediately available, can now be offered as a viable option to candidates with high-risk acute leukemias.
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