Survival of AML patients receiving HLA-matched sibling donor allogeneic bone marrow transplantation correlates with HLA-Cw ligand groups for killer immunoglobulin-like receptors

• DOI: 10.1038/sj.bmt.1705609
• Publication Date: 2007-02-19T16:13:02Z
• Authors: R M Sobecks; E J Ball; J P Maciejewski; L A Rybicki; S Brown; M Kalaycio; B Pohlman; S Andresen; K S Theil; R Dean; B J Bolwell
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Histocompatibility Testing; Graft vs Leukemia Effect; HLA-C Antigens; Middle Aged; 3. Good health; Killer Cells, Natural; Leukemia, Myeloid, Acute; 03 medical and health sciences; Treatment Outcome; Humans; Transplantation, Homologous; Female; Child; Bone Marrow Transplantation

The reactivity of natural killer cells and some T-cell populations is regulated by killer immunoglobulin-like receptors (KIR) interactions with target cell HLA class I molecules. Such interactions have been suggested to influence outcomes after allogeneic hematopoietic stem cell transplantation, particularly for myeloid malignancies and with T-cell depletion. Donor KIR genotypes and recipient HLA KIR ligands were analyzed in 60 AML patients receiving T-cell replete, HLA-matched-related donor allogeneic bone marrow transplants. Patients were categorized according to their HLA inhibitory KIR ligand groups by determining whether or not they expressed: HLA-A3 or -A11; HLA-Bw4 and HLA-Cw groups (homozygous C1, homozygous C2 or heterozygous C1/C2). Heterozygous C1/C2 patients had significantly worse survival than those homozygous for C1 or C2 (5.8 vs 43.5 months, respectively, P=0.018) and the C1/C2 group had a higher relapse rate (47 vs 31%, respectively, P=0.048). Multivariate analysis found C1/C2 status to be an independent predictor for mortality (P=0.007, HR 2.54, confidence interval 1.29-5.00). C1/C2 heterozygosity was also associated with a delayed time to platelet engraftment, particularly for those with concurrent HLA-Bw4 expression (P=0.003). Since C1/C2 heterozygotes have a greater opportunity to engage inhibitory KIRs than do C1 or C2 homozygotes, they may more effectively inhibit KIR-positive NK- and T-cell populations involved in graft vs leukemia responses.