Prognosis after unmanipulated HLA-haploidentical blood and marrow transplantation is correlated to the numbers of KIR ligands in recipients.
OBJECTIVE
The goal of this study was to explore the role of NK cell alloreaction in predicting prognosis under unmanipulated HLA-haploidentical blood and marrow transplantation and examine whether the presence of any individual donor-activating KIR gene had an influence on the clinical outcome.


METHODS
We studied the HLA and KIR genotype of 64 donor-recipient pairs, who underwent transplantation.


RESULTS
In contrast to Perugia's KIR ligand-ligand mismatch model or Handgretinger's KIR receptor-ligand mismatch model or Bignon's KIR gene-gene mismatch model between donor-recipient pairs, we found that the cumulative incidence of 3-yr disease-free survival (DFS), overall survival (OS), and transplantation-related mortality (TRM) were best predicted by the number of KIR ligands carried by patients (HR 0.355, 95% CI 0.186-0.678, P = 0.002 for DFS; HR 0.445, 95% CI 0.233-0.848, P = 0.014 for OS; HR 0.450, 95% CI 0.219-0.926, P = 0.030 for TRM). Moreover, an analysis of KIR ligand numbers was found to be correlative in patients with lymphoid malignancy. The KIR ligand-ligand mismatch model is a good predictor of acute graft vs. host disease (aGVHD; HR 3.812, 95% CI 1.667-8.720, P = 0.002). Meanwhile, the presence of donor-activating KIR2DS3 also contributed significantly to acute (HR 2.967, 95% CI 1.265-6.958, P = 0.012) and chronic GVHD (HR 2.541, 95% CI 1.127-5.730, P = 0.025).


CONCLUSIONS
These data indicate that prognosis after transplantation is associated with the numbers of KIR ligands in recipients and T-cell alloreaction may play a predominant role in this model.
Zhao
Xiang-Yu
XY
Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China.
Huang
Xiao-Jun
XJ
Liu
Kai-Yan
KY
Xu
Lan-Ping
LP
Liu
Dai-Hong
DH
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D054340:Receptors, KIR; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D006680:HLA Antigens; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR