Haploidentical hematopoietic cell transplantation

Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for nearly all patients to benefit from HCT when a HLA genotypically matched sibling is not available. Initial results with the use of mismatched allografts led to limited enthusiasm due to GVHD and infectious complications resulting in unacceptable treatment-related morbidity and mortality. Recent advances with effective T-cell depletion, the use of ‘megadoses’ of stem cells, better antimicrobial therapy and reduced intensity conditioning has significantly decreased the early transplant-related mortality and GVHD. These modifications also enabled robust and prompt engraftment and led to enhancing the therapeutic benefits of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution causing post-transplant infectious complications and relapse remain, limiting the efficacy of haploidentical transplant. Preliminary data have demonstrated the great potential in the use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GVHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched donors or natural killer (NK) alloreactive donors may greatly increase the donor availability and open a way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant with minimal risk of GVHD, while preserving effective GVL activity and promoting prompt immune reconstitution.