Abstract
Several pretransplant factors, including CRP (C-reactive protein) levels, reflect the risk of complications after allogeneic stem cell transplantation. IL-6 induces CRP increase, and we therefore investigated the effects of pretransplant IL-6, soluble IL-6 receptors, IL-6 family cytokines and CRP serum levels on outcome for 100 consecutive allotransplant recipients. All patients had related donors, none had active infections and 99 patients were in complete remission before conditioning. The incidence of acute graft versus host disease (aGVHD) requiring treatment was 40%, survival at Day +100 82%, and overall survival 48%. Despite a significant correlation between pretransplant CRP and IL-6 levels, only CRP levels significantly influenced transplant-related mortality (TRM). However, CRP did not influence overall survival (OS). Pretransplant IL-31 influenced late TRM. Finally, there was a significant association between pretransplant IL-6 and early postconditioning weight gain (i.e., fluid retention), and this fluid retention was a risk factor for aGVHD, TRM and OS. To conclude, pretransplant CRP, IL-31 and early posttransplant fluid retention were independent risk factors for TRM and survival after allotransplantation.
Highlights
Graft versus host disease (GVHD) and severe infections are the most important causes of non-relapse mortality after allogeneic stem cell transplantation (ASCT) [1,2]
Taken together with our previous studies our present observations suggest that the preconditioning CRP levels function as a risk factor that integrates the pro-inflammatory effects of several pretransplant characteristics, including serum IL-6 levels that showed significant associations in univariate analyses, correlated with CRP levels and even may serve as a therapeutic target in acute graft versus host disease (aGVHD) [52]
This study confirms that elevated CRP level above baseline increases the risk of early but not late death due to transplant related mortality, but it is not associated with an increased risk of GVHD
Summary
Graft versus host disease (GVHD) and severe infections are the most important causes of non-relapse mortality after allogeneic stem cell transplantation (ASCT) [1,2]. The risk of GVHD is influenced by pre-existing patient-, donor- and disease-specific factors as well as the pretransplant conditioning treatment and GVHD prophylaxis. Several studies suggest that specific single nucleotide polymorphisms (SNP) in Interleukin-6 (IL-6) genes influence the risk and severity of acute GVHD [4]. The IL-6 cytokine family includes IL-6 together with IL-11, IL-27, IL-31, Leukemia inhibitory factor (LIF), Oncostatin M (OSM), Ciliary neutrophilic factor (CNTF), Cardiotrophin-1, Cardiotrophin-like-cytokine and Neuropoietin [12]. All these cytokines bind to receptors utilizing gp130 for signal transduction and are involved in immunoregulation [13,14,15]. Cross-reactivity between other IL-6 family cytokine receptors is possible [15,17]
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