Human leukocyte antigen-haploidentical stem cell transplantation using T-cell-replete bone marrow grafts

Once considered too dangerous for all but the sickest of patients, partially human leukocyte antigen (HLA)-mismatched, or HLA-haploidentical, related donor bone marrow transplantation (haploBMT) has seen a revival, thanks to the reduced intensity conditioning (RIC) regimens and graft-versus-host disease (GVHD) prophylaxis with high-dose posttransplantation cyclophosphamide (PT/Cy).

RIC haploBMT with high-dose PT/Cy is associated with a cumulative incidence of acute grades II-IV GVHD of approximately 30% and incidences of chronic GVHD and nonrelapse mortality (NRM) less than 15%. These results have been confirmed in single and multicenter clinical trials. PT/Cy appears to nullify the detrimental effects of HLA mismatching on the outcome of haploBMT, thereby permitting the selection of haplo donors based upon criteria other than HLA matching. Overall and event-free survivals of RIC haploBMT compare favorably to the outcomes of RIC unrelated adult donor or umbilical cord blood stem cell transplantation.

With its improved toxicity profile, haploBMT is a feasible alternative for patients who lack an HLA-matched donor and can now be applied to treat patients with nonmalignant disorders.