Haploidentical HLAmismatched related donors

Related donors sharing one HLA haplotype, but with a greater level of HLA disparity have also been used.48-50,79,81,83,84,90 The greater level of disparity is associated with increased engraftment failure, GVHD, and transplant-related mortality (TRM).76,87,91 Drobyski and colleagues83 found that matched, unrelated-donor transplants had better outcomes than related donors, with more than one HLA mismatch for class I (A,B) or class II (DRB1*,DQB1*). Improved results may be obtained with more extensive GVHD prophylaxis, rigorous donor T cell depletion, and high stem cell doses.48-50,79 Ruggeri and colleagues48,49 found that NK cells can have a profound effect in patients receiving rigorously T-cell-depleted stem cells from single haplotype matched donors. In patients who lacked an HLA ligand for an inhibitory KIR present in the stem cell donor (see Table 93.1), donor NK cells capable of killing patient lymphoblasts were found. In patients with myeloid disease, especially AML, KIR epitope mismatched transplants had increased engraftment and lower relapse rates than did KIR epitope matched cases. Leung and col-leagues,50 in a study of pediatric patients, reported a stronger correlation by testing donor cells for KIR expression and extended the observation to ALL patients. The authors suggest that when inhibitory KIR receptors of donor NK cells are not engaged by recipient ligands they are able to mediate a strong GVL effect and may also promote engraftment. Whether a similar benefit may apply in unrelated stem cell transplants is not established since conflicting studies have been reported.92-95

0 0

Post a comment