Impact of HLA-G polymorphism on the outcome of allogeneic hematopoietic stem cell transplantation for metastatic renal cell carcinoma - Role of intra-Clonal HEterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias Accéder directement au contenu
Article Dans Une Revue Bone Marrow Transplantation Année : 2018

Impact of HLA-G polymorphism on the outcome of allogeneic hematopoietic stem cell transplantation for metastatic renal cell carcinoma

R Crocchiolo
  • Fonction : Auteur
O Ringden
  • Fonction : Auteur
D Blaise
  • Fonction : Auteur
B Omasic
  • Fonction : Auteur
B Mazzi
  • Fonction : Auteur
C Picard
  • Fonction : Auteur
S Trinca
  • Fonction : Auteur
L Barkholt
  • Fonction : Auteur
J Peccatori
  • Fonction : Auteur
S Gregori
  • Fonction : Auteur
G Amodio
  • Fonction : Auteur
K Fleischhauer
  • Fonction : Auteur
F Ciceri
  • Fonction : Auteur
M. Bregni
  • Fonction : Auteur

Résumé

Renal cell carcinoma (RCC) is particularly sensitive to immune intervention. HLA-G, a non-classical HLA class I molecule with immunomodulatory properties, has been studied with regard to outcome after hematopoietic stem cell transplantation (HSCT), in particular the 14 bp insertion/deletion polymorphism in the 3' untranslated region. Here we analyzed n=56 patients affected by metastatic RCC who received an allogeneic HSCT between 1998 and 2006 in Milano, Marseille, Clermont-Ferrand and Stockholm. The 14 bp polymorphism was analyzed in correlation with overall survival (OS), PFS, acute and chronic GvHD. With a median follow-up of 13 years, a trend towards better outcome was observed when homozygosity for the 14bp-del allele was present: multivariate hazard ratio was 0.50 (95% confidence interval (CI): 0.23-1.13; P=0.10) and 0.57 (95% CI: 0.26-1.26; P=0.17) for OS and PFS, respectively, when 14bp-del/del was compared with 14bp-ins/X. Further exploratory analysis revealed a significant association between T/C at p3003 and improved OS (P=0.05) and PFS (P=0.006) compared with T/T. To our knowledge this is the first study on HLA-G and outcome after HSCT for a solid malignancy. After a coordinated multicenter study, we found that the more tolerogenic polymorphisms (14bp-del/del) is associated with better PFS and OS. The finding on p3003 deserves further investigation.Bone Marrow Transplantation advance online publication, 13 November 2017; doi:10.1038/bmt.2017.243.

Dates et versions

hal-01658019 , version 1 (07-12-2017)

Identifiants

Citer

R Crocchiolo, O Ringden, J.O Bay, D Blaise, B Omasic, et al.. Impact of HLA-G polymorphism on the outcome of allogeneic hematopoietic stem cell transplantation for metastatic renal cell carcinoma. Bone Marrow Transplantation, 2018, 53 (2), pp.213-218. ⟨10.1038/bmt.2017.243⟩. ⟨hal-01658019⟩
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