Optimal response to thalidomide in a patient with thalassaemia major resistant to conventional therapy.

Beta-thalassaemia major is a hereditary anaemia resulting from defects in β-globin production. The coexistence of hereditary persistence of foetal haemoglobin (HbF) during adult life in patients with β-thalassaemia reduces the severity of the disease; these patients have a mild disorder, sometimes not even requiring chronic transfusions. The clinical benefit of increased HbF, first inferred in 19761, is due to a decrease in the imbalance between β and non-β-chains and the consequent reduction of haemolysis. Many drugs have been studied as inducers of HbF for patients with β-thalassaemia and sickle cell disease. Hydroxyurea is currently used in moderate to severe forms of sickle cell disease2,3 and in some cases of thalassaemia intermedia4,5. Other inducers of HbF synthesis, such as butyrate6, 5-azacytidine7 and, more recently, decitabine, have also been shown to induce HbF in patients with sickle cell disease8. However, these HbF inducers have shown only a modest effect in the majority of β-thalassaemia patients as well as some degree of toxicity. As a result, they have not been used routinely in clinical practice. Thalidomide, a drug known for its immunomodulating and anti-angiogenic properties, has recently been demonstrated to induce γ-globin gene expression and to increase the proliferation of erythroid cells9,10. Only one patient affected by β-thalassaemia major treated successfully with thalidomide has been described so far11. We report here the case of a young girl with β-thalassaemia (β+/β°) in a very severe clinical condition who could not be given any further transfusions because of the occurrence of severe post-transfusion reactions and who showed an outstanding response to thalidomide.