High plasma IL-6 levels following haploidentical allogeneic hematopoietic stem cell transplantation post-transplant cyclophosphamide as predictor of early death and worse outcome.

INTRODUCTION: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) can be used as an alternative procedure in the absence of HLA-compatible donors. The use of high doses of cyclophosphamide after infusion improves the prognosis and eliminates the need for T cell depletion in vivo. Among the main complications of haplo-HSCT are acute graft-versus-host disease (a-GVHD) and cytokine release syndrome (CRS). This is a systemic inflammatory response that leads to the release of inflammatory proteins, including IL-6. This syndrome has several clinical features, with mild to severe symptoms. This study aimed to compare plasma IL-6 levels in patients submitted to different HSCT types and to associate them with the presence of acute graft versus host disease (a-GVHD), CRS and survival. METHODS: A total of 84 patients (22 haploidentical and 62 non-haploidentical) were evaluated at different times. The IL-6 levels in haplo and non-haplo-HSCT recipients were measured before transplantation and on days D7, D14, D28, D60, and D100. RESULTS: IL-6 levels were higher in haplo-HSCT recipients than in non-haplo-HSCT recipients, remaining elevated from D14 until D100 (P = 0.006) and a cut-off ≥11 pg/mL on D7, which is related to worse overall survival. In our study, we found no association with a-GVHD (P = 0.239), a common complication of this type of transplant, but we found a relationship between the increase in IL-6 and CRS (P = 0.021). CONCLUSION: IL6 can be used as a biomarker for patients submitted to haplo-HSCT, allowing clinical interference in patients having levels of IL-6 times larger than normality values, avoiding early death in this group of patients.

The effects of gene polymorphisms on susceptibility to acute GVHD and survival of allogeneic HSCT recipients: IL-10 gene polymorphisms as a more accessible target to predict prognosis.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic modality commonly used to treat hematological and immunological disorders. Among the main complications of allo-HSCT is the acute graft-versus-host disease (a-GVHD), a condition which accounts for a high incidence of mortality. Several genes encoding inflammatory mediators may present polymorphisms, which have been implicated in the risk of developing a-GVHD. In our study, we investigated the association between genotypes of cytokine-encoding genes and the incidence and severity of a-GVHD and survival of HSCT recipients. No statistically significant association was found between IL and 6-174 G/C, INF-γ + 874 T/A, TNF-α -238 A/G, -308 A/G and IL-10-819C/T, -592 A/C polymorphisms and the presence or severity of a-GVHD. A higher risk of a-GVHD was associated with the IL-10-1082 GG genotype compared to the AA + AG genotypes of recipients and donors. The IL-10-1082 genotype can be used as a prognostic determinant to predict which HSCT recipient will be more responsive to the transplant. Thus, cytokine gene assays may be useful in the individualization of prophylactic regimens and for an appropriate selection of immunosuppressants based on the HSCT recipient's responsiveness.