Haploidentical transplantation for leukemia

Abstract

Hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-haploidentical family members offers a potential cure for patients in need of allogeneic immunotherapy who have no immediate access to an HLA-matched donor. The use of ex vivo T-cell-depleted stem cells combined with immuno-myeloablative conditioning has enabled durable donor engraftment with a low incidence of acute graft-versus-host disease despite the HLA disparity. Moreover, additional transplant techniques involving in vivo T-cell depletion and reduced-intensity conditioning have further minimized the risks. However, a major drawback is delayed immune reconstitution leading to infections and high relapse rates, prompting significant research efforts focused on improving recovery in the post-transplant period. Infusions with donor lymphocytes are common, though newer manipulations with a focus on donor natural killer cells hold great promise, as do other modified donor T-cell infusions. Success of these new procedures will make haploidentical transplants safer and more effective, further broadening its appeal.

Figure 1. NK cell activity is regulated by the balance of activating and inhibitory KIR and KIR ligands

(A) NK cell does not lyse target cell, because there is an inhibitory signal via inhibitory KIR/KIR ligand. (B) Even if there is a signal via activating KIR/KIR ligand, activating signal is canceled by an inhibitory signal from inhibitory KIR. (C) If activation via activating KIR/KIR ligand is not prevented by an inhibitory signal, the target cell is lysed.