Association of donor and recipient single-nucleotide polymorphisms of interleukin-1 gene with outcomes after allogeneic hematopoietic stem cell transplantation in childhood

Purpose Complications such as graft-versus-host disease (GVHD), hepatic sinusoidal obstruction syndrome, and infections compromise the success of allogeneic hematopoietic stem cell transplantation (HSCT) as a treatment modality for malignant or genetic diseases. Identification of beneficial non-human leukocyte antigens (HLA), such as cytokines, is one approach to reduce the rate of unintended events. This study investigated the association between single-nucleotide polymorphisms (SNPs) of the gene of the proinflammatory cytokine interleukin-1 (IL-1) and treatment outcomes after allogeneic HSCT in a pediatric population. Methods In our single-center study, we retrospectively analyzed a cohort of 270 children and their respective donors. They underwent allogeneic HSCT for the first time, and their conditioning regimen was myeloablative in all cases. We employed polymerase chain reaction to genotype the SNPs of IL-1α-889 (C/T), IL-1β-511 (C/T), and IL-1β-31 (C/T). The outcome measures included overall survival (OS), event-free survival (EFS), relapse rate (RR), transplant-related mortality (TRM), and the occurrence of acute or chronic GVHD. Results The distribution of IL-1-α-889 genotypes was as follows: we observed the CC genotype in 124 of 256 recipients (48.4%) and 132 of 270 donors (48.9%). We detected the CT genotype in 115 patients (44.9%) and 114 donors (42.2%) and found the homozygous TT genotype in 17 children (8.9%) and 24 of their donors (8.9%). The incidence of moderate or severe acute GVHD was significantly decreased in recipients with the TT genotype (4% (TT) versus 25% (CC/CT); p = 0.028). We found no significant SNP IL-1α-889 (A/T) associations for chronic GVHD, RR, TRM, EFS, and OS. For the other genotypes analyzed, IL-1β- 511 (A/T) and IL-1β-31 (A/T), we also found no significant associations for acute and chronic GVHD, RR, TRM, EFS, and OS, neither in donors nor in recipients. The results of the multivariate analyses showed a marginal significance that IL-1α-889 might be an independent risk factor for acute GVHD. Conclusion Our study identified the donor IL-1α-889 CC/CT genotype as a genetic risk factor for developing moderate to severe acute GVHD (grades II-IV) in pediatric patients who underwent allogeneic HSCT. Once confirmed in further studies, these results may suggest revising prophylactic measures to reduce acute GVHD risk in children.