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

• Published in: Bone marrow transplantation (Basingstoke) 2018-02, Vol.53 (2), p.213-218
• Main Authors: Crocchiolo, R, Ringden, O, Bay, J-O, Blaise, D, Omasic, B, Mazzi, B, Picard, C, Trinca, S, Barkholt, L, Peccatori, J, Gregori, S, Amodio, G, Fleischhauer, K, Ciceri, F, Bregni, M
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; 631/67/580; 692/700/459; Adult; Aged; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Care and treatment; Cell Biology; Cell proliferation; Clonal deletion; Confidence intervals; Correlation analysis; Diagnosis; Female; Gene deletion; Genetic polymorphisms; Graft-versus-host reaction; Hematology; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Histocompatibility antigen HLA; HLA-G Antigens - genetics; Homozygosity; Human health and pathology; Humans; Immunomodulation; Insertion; Internal Medicine; Kidney cancer; Life Sciences; Male; Malignancy; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; original-article; Polymorphism; Polymorphism, Genetic - genetics; Public Health; Renal cell carcinoma; Stem cell transplantation; Stem Cells; Survival Rate; Transplantation; Treatment Outcome; Young Adult
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/bmt.2017.243

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.