Background Thalidomide has been reported as a promising treatment for reducing transfusion volume in adults with β-thalassemia. However, the evidence about the safety and efficacy of thalidomide on children with transfusion dependent β-thalassemia (TDT) is scarce. Methods Seventy-seven children with TDT treated with thalidomide at least for 6 months were included and retrospectively analyzed. Oral dose was started at 2.5 mg•kg-1•d-1 Blood volume for maintenance of hemoglobin above 90 g•L-1 compared with pre-treatment volume is the evaluation index for response. Results After the sixth month treatment, 51/77 (66.2%) maintained Hb over 90 g•L-1 without transfusion. Adverse events were reported in 48 (63.2%) patients.Age, sex, genotype category, dosage and transfusion interval before thalidomide treatment were not correlated to treatment response. The AUC was 0.806 for the HbFat the third month of treatment in predicting probability of major responders at the sixth month treatment. Based on Youden’s index algorithm in the ROC curve, 47.298 g•L-1 was the optimal cut-off value of the HbFat the third month of treatment in predicting major responders at the sixth month treatment, with sensitivity of 67.5%, specificity of 93.3%. Conclusions The dose of thalidomide between 2.5 mg•kg-1•d-1to 3.6 mg•kg-1•d-1 is effective in TDT children. Severe side effects are uncommon. HbF concentration of 47.298 g•L-1 at the third month is recommended as the predictor for further major responders.

Objective: Cytokine storms are central to the development of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Previous studies showed that single nucleotide polymorphisms (SNPs) of cytokine genes may be associated with the development of EBV-HLH in children. We investigated the associations between SNPs and haplotypes of interleukin-2 receptor subunit alpha (IL2RA), interleukin-10 (IL-10), interferon gamma (IFN-γ), IFN regulatory factor 5 (IRF5), and C-C chemokine receptor 2 (CCR2) and susceptibility to EBV-HLH in children. Methods: 66 children with EBV-HLH and 58 healthy EBV-seropositive controls were enrolled in the study. SNPs of IL2RA rs2104286, rs12722489, and rs11594656, IL-10 rs1800896, rs1800871, and rs1800872, IFN-γ rs2430561, IRF5 rs2004640, and CCR2 rs1799864 were assayed and genotyped using the SNaPshot technique. Results: The frequencies of the AA genotype and A allele of IL2RA rs2104286 and IL-10 rs1800896, and the CC genotype and C allele of IL-10 rs1800872 were significantly higher in the EBV-HLH group compared with those in the control group, respectively. The frequencies of genotypes and alleles of IL2RA rs2104286, IL-10 rs1800871, IFN-γ rs2430561, IRF5 rs2004640, and CCR2 rs1799864 were similar in both groups. In addition, the IL2RA AGT (rs2104286-rs12722489-rs11594656) and IL-10 ACC (rs1800896-rs1800871-rs1800872) haplotypes were also significantly more frequent in the EBV-HLH group. Conclusions: The SNPs of IL2RA rs2104286, IL-10 rs1800896 and rs1800872 and the haplotypes of IL2RA AGT and IL-10 ACC are highly associated with susceptibility to EBV-HLH in children.