Discussion
hemolysis, constipation
ADVERSE EVENTS, HEMOLYSIS, IRON OVERLOAD, ADVERSE EVENT
The present study evaluated the long-term safety and efficacy of thalidomide therapy with encouraging results in a relatively large number of TDT patients. Thalidomide, compared to transfusions, is more convenient and economical because transfusions induce iron overload which can be prevented via expensive iron chelation therapy. During long-term follow-up, the efficacy of thalidomide in terms of hematological response was stable and sustained over time, and no reduction in response was observed, signifying its aided benefit to TDT patients requiring continued treatment.The efficacy of thalidomide reported in our study in terms of complete blood transfusion independence in 76.7% patients is consistent with a recently published meta-analysis reporting pooled response rate of nine studies, showing complete cessation of blood transfusion in 52% of TDT patientsA significant reduction in mean serum ferritin level and LDH level was observed during the study period. The observed reduction in serum ferritin level could be attributed to reduced transfusion requirements as well as improved erythropoiesis and increased RBC production. While, a significant decline in LDH level may be attributed to a decrease in hemolysis due to the increased life span of RBCs by thalidomideA significant decline in total bilirubin levels following treatment with thalidomide was observed at 6th month of treatment, whereas, no statistically significant difference was found at 30th month of treatment. These findings are in contrast with the findings of Ansari et al., who reported no statistically significant difference following treatment with thalidomide and HU for 6 monthsThe adverse events of thalidomide were mainly mild and tolerable, demonstrating that thalidomide could be a promising drug for TDT. Mild adverse events were reported in 9% of patients, of which constipation was the most frequent adverse event which resolved after symptomatic treatment. These findings are consistent with previous reports of thalidomideIn light of the findings of this study including attainment of transfusion independence by a large number of patients (76.7%), a significant decline in serum ferritin and LDH levels, reduction in spleen size and liver size, improvement in Hb level and no unfavorable effects of thalidomide on renal and hepatic function, we consider thalidomide, a promising drug for improving Hb levels and reduction/cessation of transfusion requirement in TDT patients. Furthermore, repositioning of thalidomide to increase HbF in β-thalassemia appears very promising based on the following considerations: first, there is a clear clinical pharmacological target, that is an increase of HbF; second, there is no doubt that an increase of HbF decreases transfusion burden; and lastly, there is robust evidence in the literature that in case of HU, in vitro response predicts in vivo response. To this end, thalidomide is particularly the most relevant drug that can be administered in TDT patients based on the proven long-term safety and efficacy observed in this study.