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

Bone Marrow Transplantation volume 53, pages 213–218 (2018)Cite this article

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Abstract

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.

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Acknowledgements

We are grateful to the Solid Tumor Working Party of the EBMT for financial support to the study.

Author information

Author notes

  1. F Ciceri and M Bregni: These authors contributed equally to this work.

Authors and Affiliations

  1. San Raffaele Hospital, Milano, Italy

    R Crocchiolo, B Mazzi, S Trinca, J Peccatori, K Fleischhauer, F Ciceri & M Bregni

  2. Karolinska University Hospital, Stockholm, Sweden

    O Ringden, B Omasic & L Barkholt

  3. CHU Clermont Ferrand, Clermont Ferrand, France

    J-O Bay

  4. Institut Paoli-Calmettes, Aix-Marseille University, CNRS, INSERM, CRCM, Marseille, France

    D Blaise

  5. Aix Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins",, Marseille, France

    C Picard

  6. San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milano, Italy

    S Gregori & G Amodio

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  1. R Crocchiolo
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on behalf of the STWP and CTIWP of EBMT

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Correspondence to R Crocchiolo.

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RC is employee of MolMed S.p.A. at the time of submission. The remaining authors declare no conflict of interest

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Crocchiolo, R., Ringden, O., Bay, JO. et al. Impact of HLA-G polymorphism on the outcome of allogeneic hematopoietic stem cell transplantation for metastatic renal cell carcinoma. Bone Marrow Transplant 53, 213–218 (2018). https://doi.org/10.1038/bmt.2017.243

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