Why to chose the Haploidentical Bone Marrow Donor?
The almost always present yet overlooked donor is the haplotype matched sibling, parent, or offspring. Haploidentical Bone Marrow Donor hematopoietic cell transplantation has been evaluated for more than two decades as an alternative option for the approximately 70 percent of patients who do not have an HLA identical sibling bone marrow donor. The advantages are that nearly all patients have an immediately available Haploidentical Bone Marrow Donor and that a strong graft-versus-tumor effect may be realized with HLA disparity. Early attempts at allogeneic hematopoietic cell transplantation from haplotype matched donors were associated with significant graft-versus host disease in non–T-cell-depleted transplants and with graft rejection in T-cell-depleted products. Extensive ex vivo immune cell depletion with anti-CD3+ coated and anti-CD19+ coated microbeads, coupled with mega-dose CD34+ cells can successfully overcome the barriers to engraftment.
How to prevent graft versus-host disease?
In these protocols, the extensive T-cell depletion that largely prevented graft versus-host disease would also be expected to result in weak or no graft-versus-tumor reactions. Yet despite the lack of T-cell–mediated alloreactivity and the unfavorable prognostic features at the time of transplantation, relapse rates in the Perugia protocol remained at less than 18 percent and 30 percent, respectively, in AML and acute lymphoblastic leukemia (ALL) patients transplanted in complete remission.
The low rate of relapse was attributed to a strong antitumor effect mediated by donor-versus-recipient natural Killer cell alloreactivity. Transplantation from natural killer cell alloreactive donors was associated with a significantly lower leukemia relapse rate and improved overall survival; therefore, some authorities recommended selecting natural killer cell alloreactive donors for haploidentical transplantation.
However, the widespread acceptance of haploidentical hematopoietic cell transplantation remains hampered by the prolonged immune reconstitution and a high risk of serious infection. Future directions will focus on efficacy in diseases other than leukemia, developing improved conditioning regimens, and promoting effective and timely post-transplantation immune reconstitution.