HLA-haploidentical stem cell transplantation for hematologic malignancies

Abstract

Partially HLA-mismatched related, or HLA-haploidentical, donor stem cell transplantation (SCT) is a feasible therapeutic option for advanced hematologic malignancies patients who lack an HLA-matched related or unrelated donor. Advances in conditioning regimens, graft manipulation, and pharmacologic prophylaxis of graft-versus-host disease (GVHD) have reduced the risk of fatal graft failure and severe GVHD, two of the most serious complications of traversing the HLA barrier. Clinical observations reveal a potential role for natural killer (NK) cell alloreactivity in reducing the risk of relapse of acute myeloid leukemia after HLA-haploidentical SCT. NK cell infusions attempt to harness the graft-versus-leukemia effect without producing GVHD. The availability of multiple potential HLA-haploidentical related donors for most patients opens the possibility of optimizing transplantation outcome through intelligent donor selection.

Figure 1

Treatment schema for nonmyeloablative conditioning and HLA-haploidentical bone marrow transplantation. From ref. .

Figure 2

Effect of HLA-DRB1 antigen mismatch (a,c) or HLA Class I allele mismatches (b,d) in the graft-versus-host direction on relapse, non-relapse mortality (a,b) and event-free survival (c,d) after nonmyeloablative, HLA-haploidentical bone marrow transplantation with high-dose, post-transplantation cyclophosphamide.

Figure 3

The myeloablative conditioning regimen for HLA-haploidentical HSCT at Peking University. Ara-C: cytosine arabinoside; Bu: busulfan; CY: cyclophosphamide; MeCCNU: simustine; ATG: Thymoglobulin.