Interferon-gamma gene polymorphism associate with mortality and graft-versus-host disease severity in HLA-matched sibling bone marrow transplantation

BERRO M; FONCUBERTA C; JAIMOVICH G; KUSMISKY G; BESTACH Y; VITRIU A; REQUEJO A; LARRIPA I; PALAU V; RIVAS M; MARTINEZ ROLON J; PADROSO K; BELLI C

Copenhague

Congreso; 21ST Congress European Hematology Association (EHA) 2016; 2016

European Hematology Association

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with sibling donors is a life-saving intervention for patients with hematological malignancies. It is recognized that numerous genetic factors in patient and donor, including polymorphic variants of cytokine encoding genes, have been reported that contribute to the outcome of the procedure. Interferon gamma (IFNy) plays a central role in innate and adaptive immunity. IFNG gene has a regulatory element in its first intron that includes a microsatellite CA repeat which CA12 variant is associated with an increased production. Up to date there are few published data on the association between this polymorphism and allo-HSCT related complications performed in small series.Aims To evaluate the presence of the microsatellite polymorphism +875 (CA)n IFNG and its relationship with response and / or complications related to allo-HSCT.Methods Two hundred and twenty two (222) patient/donor pairs who underwent a sibling donor HSCT in our centers were genotyped for the presence of +875 (CA)n IFNG (rs3138557) variants. Transplants took place between 01/2000 and 03/2015 with a median follow up of 4.4 years. Results Median age of recipients was 33 years, being 90% ≥ 16 years old and 58% male. Prevalent diagnoses were acute myeloid leukemia 29%, acute lymphoid leukemia 23%, lymphoproliferative disorders 13%, and myelodysplastic syndrome 12%; 45% were in early stage of the disease. Myeloablative conditioning regimens were used in 59% and the prevalent source for stem cells was peripheral blood in 90% of patients. Genotypes distribution was 22% CA12/CA12, 41% CA12/CAno12 and 37% CAno12/CAno12 for recipients, and 17%, 54% and 29% for donors, respectively (Chi2 test p=0.011).When patients with genotype CAno12/CAno12, associated with low expression, were compared against the rest of genotypes, we observed that these patients developed less acute graft versus host disease (aGVHD) grades II-IV (21% vs. 37%, Fischer exact test p= 0.053),grades III-IV (6% vs. 15%, p= 0.071), chronic GVHD (26% vs 41%, p= 0.029), and a later myeloid engraftment (≥15 days: 54% vs 26%, p