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

R Crocchiolo, O Ringden, JO Bay, D Blaise, B Omasic, B Mazzi, C Picard, S Trinca, L Barkholt, J Peccatori, S Gregori, G Amodio, K Fleischhauer, F Ciceri, M Bregni, on behalf of the STWP, CTIWP of EBMT

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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.
Original languageEnglish
Pages (from-to)213-218
Number of pages6
JournalBone Marrow Transplantation
Volume53
Issue number2
DOIs
Publication statusPublished - 2018

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    Crocchiolo, R., Ringden, O., Bay, JO., Blaise, D., Omasic, B., Mazzi, B., Picard, C., Trinca, S., Barkholt, L., Peccatori, J., Gregori, S., Amodio, G., Fleischhauer, K., Ciceri, F., Bregni, M., STWP, O. B. O. T., & EBMT, CTIWP. O. (2018). Impact of HLA-G polymorphism on the outcome of allogeneic hematopoietic stem cell transplantation for metastatic renal cell carcinoma. Bone Marrow Transplantation, 53(2), 213-218. https://doi.org/10.1038/bmt.2017.243