5388 Christopher Lowrey/Arthur Nienhuis: Brief report: Treatment with azacitidine of patients with end-stage beta-thalassemia.
New England J. Med. 329 (1993), 845-848.
[Patients with beta-thalassemia major have a short life expectation. It is unusual for a patient with the most severe form of the disease to survive into adulthood. Most patients have such severe anemia that they are dependent upon transfusion. The chronic administration of large amounts of blood along with an inappropriate increase in iron absorption from the gastrointestinal tract inevitably leads to clinically significant hemosiderosis. As a result of iron overload, these patients develop abnormalities in hepatic, endocrine, and cardiac function. (Harrison)]
Regular erythrocyte transfusions form the cornerstone of treatment for patients with severe beta-thalassemia. Despite the use of iron-chelation therapy, fatal iron overload develops in many patients, even when they are under supervision and taking part in studies designed to test the effectiveness of intense chelation. Another potential consequence of long-term transfusions is the development of antierythrocyte antibodies, making effective transfusion difficult or, in rare cases, impossible.
A potential alternative to transfusion is the use of the nucleoside analogue azacitidine to stimulate transcription of the fetal globin genes by pharmacologic means and thus lead to more effective erythropoiesis. Although the mechanism of this effect is not well understood, it is believed to be related in part to the ability of the drug to inhibit methylation of newly synthesized DNA within regions that regulate the expression of globin genes. In this article the authors describe the effect of azacitidine treatment in three patients with end-stage beta-thalassemia for whom continued transfusion therapy was no longer beneficial. Treatment freed all three patients from need for transfusions. Two patients have thus far been treated for 30 months, with improvement in their clinical status and quality of life.

5387 Guido Lucarelli a.o.: Marrow transplantation in patients with thalassemia responsive to chelation therapy.
New England J. Med. 329 (1993), 840-844.
[Those] patients with homozygous beta-thalassemia, who have a good prognosis during treatment with conventional therapy, appear to have an especially high probability of hematologic cure with bone marrow transplantation, although the morbidity and mortality associated with such treatment are not established. In this study the records of all patients with thalassemia who received bone marrow transplants from HLA-identical donors in Pesaro were examined from October 1982 through May 1992. Thy authors conclude that patients with class 1 thalassemia who have HLA-identical donors available should be treated by bone marrow transplantation. This was however not a controlled trial, so one cannot directly compare the outcome with that of conventional treatment.

5394 D. Weatherall: The treatment of thalassemia - slow progress and new dilemmas. New England J. Med. 329 (1993), 877-878.
The thalassemias pose an important public health problem in many countries. In recent years there has been a great progress in determining the molecular pathology of the different forms of thalassemia and in understanding the basis for their remarkable clinical heterogeneity. This knowledge has been applied in the clinic for the detection of carriers and the prenatal diagnosis of the more severe forms, particularly beta-thalassemia. The results has been a major reduction in the number of new cases of thalassemia, notably in Greece, Italy, and the Mediterranean Islands. In the treatment the mainstays have been regular blood transfusions, the judicious use of splenectomy, and the removal of iron chelating agents. There is no doubt that the introduction of adequate transfusion regimens together with intensive iron chelation with continuous subcutaneous administration of deferoxamine has dramatically improved the outlook for children with thalassemia. There are, however, many problems with this treatment. The results from the Pesaro group suggest that bone marrow transplantation is now a genuine option for the management of severe forms of beta-thalassemia. A comment to the articles by Lucarelli a.o. and by Lowrey/Nienhuis in the same issue of the NEJM.

D. Weatherall: Thalassemia. In G. Stammatoyannopoulos/A. Nienhuis/P. Majerus/H. Varmus (ed.): The molecular basis of blood diseases. Saunders 1993.