地拉罗司对铁质积聚有多大疗效？

There are currently three iron chelating drugs approved to reduce iron burden, including ferroxamine, ferroferrione and ferriproxine. Deferrioxamine (DFO) can combine with iron in ferritin or hemosiderin, convert it into ferrioxamine molecules and be excreted by the kidneys. The production of ferrioxamine can prevent the chemical reaction of iron, thereby reducing the formation of reactive oxygen species. Desferrioxamine can be injected subcutaneously or intravenously, and the dosage is 20~60mg/kg. Since the half-life is only 20 minutes, it requires continuous administration for a long time, which is more inconvenient. Both ferriprone and deferasirox can chelate intracellular iron and more directly remove iron that generates ROS than ferroxamine. Ordroferrione is an oral drug with a half-life of 2 to 3 hours. The dose is 50 to 100 mg/kg per day, taken orally in 3 times. It has many gastrointestinal side effects. The daily dosage of deferasirox dispersible tablets is 20~30 mg/kg, once a day, and has good clinical compliance, but it is expensive. In addition to chelating intracellular iron, deferasirox is also related to the increase in hepcidin, which can reduce iron absorption in intestinal cells, so the iron removal effect is better.  

According to a retrospective study in Italy, 42.7% of patients achieved a hematological response and reduced the need for blood transfusions after receiving DFO or deferasirox chelation therapy. There may be a dynamic, bidirectional regulatory mechanism between erythropoiesis and iron overload. On the one hand, ineffective erythropoiesis can lead to increased intestinal iron absorption through reduced hepcidin secretion by the liver. On the other hand, chelation treatment of iron overload can improve erythropoiesis, increase hemoglobin levels, and reduce clinical blood transfusions.

  In addition to reducing blood transfusions, iron chelation therapy has additional effects against tumor proliferation. The researchers added the culture medium to the bone marrow cells of patients with myelodysplastic syndrome (MDS) and found that the viability of MDS-derived progenitor cells was significantly reduced, and their cloning ability was also significantly inhibited. A study of 158 patients with serum ferritin >1000 ng/mL after hematopoietic stem cell transplantation found that 23 patients who received iron chelation therapy had a higher 5-year overall survival rate (59% vs. 34%, P = 0.008) and a lower risk of recurrence (18% vs. 41%, P = 0.012) than those who did not receive chelation therapy. It can be seen that iron chelating drugs can not only provide clinical benefits through iron removal, but also provide anti-tumor proliferation effects on certain myeloid leukemias.