Impact of incompatible killer cell immunoglobulin-like receptor and its ligand on the outcome of haploidentical bone marrow transplantation.
The purpose of study was to investigate the impact of killer immunoglobulin-like receptor (KIR) and its ligand on haploidentical bone marrow transplantation. 74 cases were analyzed for the distribution frequencies and characteristics of KIR and its ligand as well as the impact of KIR ligand for the haploidentical bone marrow transplantation in terms of the overall survival, disease-free survival (DFS), GVHD and relapse. The results showed that among the 19 KIR genotypes currently nominated KIR2DL1, KIR2DL4 and KIR3DL2-3 could be detected in all the cases. Other high frequency genotypes included KIR3DP1 (98.6%), KIR2DP1 (98.6%), KIR3DL1 (97.3%) and KIR2DL3 (97.3%). Inhibitory receptor genotypes were 1.37-fold of activating receptor genotypes. KIR2DL1, KIR3DL2, KIR3DL3 and KIR2DL4 were found in all haplotypes and at least one genotype of KIR2DL2 and/or KIR2DL3 existed in all haplotypes. Among the 14 genotypes found in the test, the HLA-Cw7 was the most popular (37.8%) and the group 2 (HLA-Cw1, 3, 7, 8, 13, 14) recognized by KIR2DL2/2DL3 counted for 43.2%. The incompatibility of KIR for 32 cases of haploidentical BMT was 43.8%, of which 9/14 were KIR2DL incompatible, 5/14 were KIR2DL2 or KIR3DL1 incompatible. Among the 46 cases of haploidentical BMT, 29 cases were HLA-Cw matched and 14 cases were mismatched. The completed mismatch ratio of HLA-Cw was 30.4% and the match ratio was 63.4%. The survival rate was higher for the 14 cases of KIR genotype compatible group than the 13 cases of KIR genotype incompatible group (p = 0.032). The disease-free survival was significantly higher for the 17 cases of mismatched KIR ligands (HLA-Cw) group than the matched group (p = 0.024). The survival rate was higher in GVHD group than that in non-GVHD group when the KIR ligand was missing. The acute and severe GVHD was related to the existence of activating receptor of KIR2DS1/2DS2. The incompatibility group was accompanied with frequent acute and severe GVHD and less relapse and vice versa for the compatibility group. One patient died after BMT among the 14 mismatched KIR ligand group suffering from myelogenous leukemia while 4 patients out of 12 patients died in the matched group. It is concluded that the haploidentical BMT is characterized by mismatch between donor and recipient and its immunological reactions also features by the incompatibility of KIR genotype and missing ligand. The missing ligand for the donor KIR has strong effect on the outcome of BMT and it means a lot to analyze the KIR genotype and its ligand for the selection of best donor and prognostic evaluation in haploidentical BMT.
Duan
Lian-Ning
LN
Department of Hematology, General Hospital of Air Force, Beijing 100036, China. duanlianning@hotmail.com
Han
Hong-Xing
HX
Liu
Jing
J
Yan
Hong-Min
HM
Zhu
Ling
L
Xue
Mei
M
Ding
Li
L
Zhu
Pei-Yu
PY
Wang
Heng-Xiang
HX
Ji
Shu-Quan
SQ
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy*; D006648:Histocompatibility / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D015236:HLA-C Antigens; C040178:HLA-C*70 antigen; C047431:HLA-Cw1 antigen; D008024:Ligands; D054340:Receptors, KIR