PURPOSE OF REVIEW: Unmanipulated or CD34 selected haplotype mismatched transplantation provides the benefits of hematopoietic stem cell transplant for nearly all patients who do not have a human leukocyte antigen fully matched sibling or who urgently need transplantation. Haplotype mismatched transplant is, however, complicated by delayed immune reconstitution, leading to increased risks of fatal posttransplant opportunistic infections. This review summarizes recent investigations aimed at optimizing outcomes. RECENT FINDINGS: The graft is a megadose of positively/negatively T-cell-depleted or unmanipulated progenitor cells. Although haploidentical transplant modalities are based mainly on high-intensity conditioning regimens, recently introduced reduced-intensity regimens showed promise in decreasing early transplant-related mortality and in extending the opportunity of hematopoietic stem cell transplantation to an elderly population with more comorbidities. Natural killer cell alloreactivity reduces graft-versus-host disease while augmenting graft-versus-malignancy. Immune reconstitution was highly predictive of outcome following T-cell-depleted transplantation. SUMMARY: Mismatched/haploidentical transplant provides an alternative approach for patients with high-risk hematological malignancies or marrow failure syndromes. Overall survival and clinical outcome continue to improve. Future challenges lie in determining the safest preparative conditioning regimen, minimizing graft-versus-host disease while preserving effective graft-versus-malignancy and promoting rapid immune reconstitution.
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