The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population.
The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donor-recipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P=0.019, HR=0.329), mainly in myeloid disease (P=0.003, HR=0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P=0.034, HR=0.430) and disease-free survival (DFS) (P=0.024, HR=0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P=0.003, HR=5.046), decreased OS (P=0.004, HR=3.181) and DFS (P=0.003, HR=2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.
Wu
G Q
GQ
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Zhao
Y M
YM
Lai
X Y
XY
Luo
Y
Y
Tan
Y M
YM
Shi
J M
JM
Li
L
L
Zheng
W Y
WY
Zhang
J
J
Hu
X R
XR
Jin
A Y
AY
He
J S
JS
Xie
W Z
WZ
Ye
X J
XJ
Cai
Z
Z
Lin
M F
MF
Huang
H
H
D000293:Adolescent; D000328:Adult; D002648:Child; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D007951:Leukemia, Myeloid / Q000235:genetics / Q000628:therapy*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics; D054340:Receptors, KIR / Q000819:agonists* / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors; D055815:Young Adult
D006680:HLA Antigens; C541358:KIR2DS3 protein, human; D008024:Ligands; D054340:Receptors, KIR