Survival of AML patients receiving HLA-matched sibling donor allogeneic bone marrow transplantation correlates with HLA-Cw ligand groups for killer immunoglobulin-like receptors.
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.
Sobecks
R M
RM
Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195, USA. sobeckr@ccf.org
Ball
E J
EJ
Maciejewski
J P
JP
Rybicki
L A
LA
Brown
S
S
Kalaycio
M
M
Pohlman
B
B
Andresen
S
S
Theil
K S
KS
Dean
R
R
Bolwell
B J
BJ
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D005260:Female; D020544:Graft vs Leukemia Effect; D015236:HLA-C Antigens / Q000096:biosynthesis*; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
D015236:HLA-C Antigens