KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma Journal Article


Authors: Venstrom, J. M.; Zheng, J.; Noor, N.; Danis, K. E.; Yeh, A. W.; Cheung, I. Y.; Dupont, B.; O'Reilly, R. J.; Cheung, N. K. V.; Hsu, K. C.
Article Title: KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma
Abstract: Purpose: NK cells exhibit cytotoxicity against neuroblastoma. Gene polymorphisms governingNKcell 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 genotypemayuniquely benefit fromautologoushematopoieticstem 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. © 2009 American Association for Cancer Research.
Keywords: controlled study; treatment outcome; retrospective studies; major clinical study; overall survival; gene; progression free survival; genetic association; genotype; odds ratio; hematopoietic stem cell transplantation; medical record review; algorithms; high risk patient; risk; immunotherapy; infant; neuroblastoma; disease progression; hla antigen class 1; ligands; killer cell immunoglobulin like receptor; receptors, kir; oncogene c myb; hla antigens; autologous hematopoietic stem cell transplantation; hla gene; kir gene
Journal Title: Clinical Cancer Research
Volume: 15
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2009-12-01
Start Page: 7330
End Page: 7334
Language: English
DOI: 10.1158/1078-0432.ccr-09-1720
PUBMED: 19934297
PROVIDER: scopus
PMCID: PMC2788079
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Junting Zheng
    130 Zheng
  2. Nai-Kong Cheung
    439 Cheung
  3. Katharine C Hsu
    133 Hsu
  4. Irene Y Cheung
    73 Cheung
  5. Richard O'Reilly
    480 O'Reilly
  6. Bo Dupont
    155 Dupont
  7. Alice Yeh
    3 Yeh
  8. Nabila Noor
    1 Noor
  9. Karen E Danis
    6 Danis