Sociedad Argentina de Hematología

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Revista Argentina de Hematología


Volumen:    22    # Number : 1

Publication Date :    Enero - Abril    Year:    2018


Contribution of polymorphisms in IFNG and TNF to complications of the allogeneic hematopoietic stem cell transplantation with sibling donors

Authors: Palau V, Berro M, Bestach Y, Rivas MM, Foncuberta C, Vitriu A, Remaggi G, Martínez Rolón J, Jaimovich G, Requejo A, Padros K, Rodríguez MB, Kusminsky G, Larripa I, Belli C.

Abstract: Complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) include variable engraftment times, acute (aGVHD) and chronic (cGVHD) graft-versus-host diseases, bacterial infections and reactivation of cytomegalovirus (CMV), among others. The existence of polymorphisms in non-HLA genes that encode pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF) and interferon gamma (IFNG) would condition the appearance of these complications. The impact of polymorphic variants +1349 CAn of INFG gene and -308 G/A of TNF was evaluated on the engraftment and GVHD in 148 allo-HSCT recipients with sibling donors. In the multivariate analysis, the genotype CAno12/no12 (low production) of INFG (OR 3.9, p=0.003), bone marrow (BM) as source of progenitor cells (OR 4.6, p=0.013) and bacteremia (OR 3.0, p=0.033) maintained their predictive power with respect to late engraftment (≥15 days). Genotype of low IFNG production (OR 0.1, p=0.008), bacteremia (OR 3.3, p=0.048) and presence of CMV (OR 3.3, p=0.046) showed a significant association with aGVHD 3-4. And with respect to cGVHD, the genotype -308 GG (low production) of TNF (OR 3.3, p=0.038), PB as source (OR 5.0, p=0.028), myeloablative conditioning (OR 3.3, p=0.014) and previous aGVHD 2-4 (OR 2.6, p=0.029). Although it is necessary to confirm these findings, the genotype of lower IFNG production was associated with a later engraftment and less severe aGVHD and genotypes of lower TNF production was related to a higher incidence of cGVHD contributing to the development of complications in allo-HSCT.

Key words: hematopoietic stem cell transplantation, IFNG, TNF, polymorphisms.

Pages : 28-33

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