PMID- 19934297
OWN - NLM
STAT- MEDLINE
DCOM- 20100308
LR  - 20211020
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 23
DP  - 2009 Dec 1
TI  - KIR and HLA genotypes are associated with disease progression and survival 
      following autologous hematopoietic stem cell transplantation for high-risk 
      neuroblastoma.
PG  - 7330-4
LID - 10.1158/1078-0432.CCR-09-1720 [doi]
AB  - PURPOSE: NK cells exhibit cytotoxicity against neuroblastoma. Gene polymorphisms 
      governing NK cell function, therefore, may influence prognosis. Two highly 
      polymorphic genetic loci instrumental in determining NK cell responses encode the 
      NK cell killer immunoglobulin-like receptors (KIR) and their class I human 
      leukocyte antigen (HLA) ligands. We hypothesized that patients with a "missing 
      ligand" KIR-HLA compound genotype may uniquely benefit from autologous 
      hematopoietic stem cell transplantation (HSCT). EXPERIMENTAL DESIGN: One hundred 
      sixty-nine patients treated with autologous HSCT for stage IV neuroblastoma 
      underwent KIR and HLA genotyping. Patients were segregated according to the 
      presence or absence of HLA ligands for autologous inhibitory KIR. Univariate and 
      multivariate analyses were done for overall and progression-free survival. 
      RESULTS: Sixty-four percent of patients lacked one or more HLA ligands for 
      inhibitory KIR. Patients lacking a HLA ligand had a 46% lower risk of death 
      [hazard ratio, 0.54; 95% confidence interval (95% CI), 0.35-0.85; P = 0.007] and 
      a 34% lower risk of progression (hazard ratio, 0.66; 95% CI, 0.44-1.0; P = 0.047) 
      at 3 years compared with patients who possessed all ligands for his/her 
      inhibitory KIR. Among all KIR-HLA combinations, 16 patients lacking the HLA-C1 
      ligand for KIR2DL2/KIR2DL3 experienced the highest 3-year survival rate of 81% 
      (95% CI, 64-100). Survival was more strongly associated with "missing ligand" 
      than with tumor MYCN gene amplification. CONCLUSION: KIR-HLA immunogenetics 
      represents a novel prognostic marker for patients undergoing autologous HSCT for 
      high-risk neuroblastoma.
FAU - Venstrom, Jeffrey M
AU  - Venstrom JM
AD  - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New 
      York 10065, USA.
FAU - Zheng, Junting
AU  - Zheng J
FAU - Noor, Nabila
AU  - Noor N
FAU - Danis, Karen E
AU  - Danis KE
FAU - Yeh, Alice W
AU  - Yeh AW
FAU - Cheung, Irene Y
AU  - Cheung IY
FAU - Dupont, Bo
AU  - Dupont B
FAU - O'Reilly, Richard J
AU  - O'Reilly RJ
FAU - Cheung, Nai-Kong V
AU  - Cheung NK
FAU - Hsu, Katharine C
AU  - Hsu KC
LA  - eng
GR  - UL1RR024996/RR/NCRR NIH HHS/United States
GR  - R01 HL088134-01A1/HL/NHLBI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 HL088134/HL/NHLBI NIH HHS/United States
GR  - UL1 RR024996/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091124
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (HLA Antigens)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Algorithms
MH  - Child, Preschool
MH  - Disease Progression
MH  - *Genotype
MH  - HLA Antigens/*genetics
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Immunotherapy/methods
MH  - Infant
MH  - Ligands
MH  - Neuroblastoma/*genetics/mortality/*therapy
MH  - Odds Ratio
MH  - Receptors, KIR/*genetics
MH  - Retrospective Studies
MH  - Risk
MH  - Treatment Outcome
PMC - PMC2788079
MID - NIHMS147321
COIS- Disclosure of Potential Conflicts of Interest There are no relevant conflicts of 
      interest to disclose.
EDAT- 2009/11/26 06:00
MHDA- 2010/03/10 06:00
PMCR- 2010/12/01
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 1078-0432.CCR-09-1720 [pii]
AID - 10.1158/1078-0432.CCR-09-1720 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Dec 1;15(23):7330-4. doi: 10.1158/1078-0432.CCR-09-1720. 
      Epub 2009 Nov 24.