Adequate Chelation Therapy Research Articles

Thalassemia intermedia: Revisited

Thalassemia intermedia encompasses a wide clinical spectrum of beta-thalassemia phenotypes. Some thalassemia intermedia patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with thalassemia intermedia are rarely seen in thalassemia major, including extramedullary hematopoiesis, leg ulcers, gallstones and thrombophilia. Prevention of these complications, possibly with blood transfusion therapy, is ideal since they may be difficult to manage. Currently, many patients with thalassemia intermedia receive only occasional or no transfusions, since they are able to maintain hemoglobin levels between 7–9 g/dl; the risk of iron overload, necessitating adequate chelation therapy, is also a contributing factor. At present, there are no clear guidelines for initiating and maintaining transfusions in thalassemia intermedia for the prevention or treatment of complications. Here, we review the major clinical complications in thalassemia intermedia and suggest some therapeutic strategies based on retrospective clinical observations.

Sideroblastic anaemias.

Sideroblastic anaemias.

Chelation treatment of neurological Wilson's disease

The results of chelation treatment of 137 patients presenting with neurological Wilson's disease are described, together with the more commonly observed toxic reactions to the various drugs employed. Fifty-seven patients made an excellent response to treatment and became symptom free. Thirty-six patients made a good recovery, but were left with some minor neurological deficit. Twenty-four patients had a poor response: although the disease process was arrested they were left more or less disabled. Twenty patients died: nine had little or no treatment, but 11 died despite apparently adequate chelation therapy. There was no obvious reason for this failure. The liver copper level was estimated in six of these patients: it was still significantly elevated in only one, but in all four in whom it was possible to make the determination, the concentration of copper in the basal ganglia was in excess of 45 micrograms/g wet weight. It was not apparent why adequate therapy failed to remove copper from the brains of these patients. There was no obvious clinical, histological or biochemical indicator of failure to respond to treatment. Initial deterioration before improvement was seen in 30 patients: the prognosis for a useful recovery was not necessarily worse than that in patients who did not show this phenomenon.

Bone marrow transplantation in adult thalassemia

Early trials of allogeneic marrow transplantation for homozygous thalassemia were disappointing in patients older than 16, with four of six patients dying early of graft-versus-host disease-related complications, one patient dying at 9 months of infection due to graft failure, and one dying at 6 years of recurrent thalassemia. Three classes of risk could be identified in analyses of results of transplantation in younger patients using the criteria of degree of hepatomegaly, the presence or absence of portal fibrosis, and a history of adequate or inadequate chelation therapy. Patients for whom all three criteria were adverse constituted a very high risk group (class 3) for marrow transplantation. On the basis of these analyses, a conditioning regimen was designed that yielded superior results for class 3 patients under 17 years of age. Most patients older than 16 years presenting for transplantation have disease characteristics that place them in class 3 and, because of the improved results with the new class 3 regimen in younger patients, a study was designed to treat patients older than 16 years using treatment regimens assigned on the basis of disease class. Twenty patients were treated using this protocol and, with a minimum follow-up of 9 months, there have been three early deaths, one patient has recurrent thalassemia, and 16 patients are alive disease-free. The actuarial probabilities of survival, disease-free survival, and rejection are 0.85, 0.80, and 0.05, respectively, with a survival plateau extending from 6 months to 3 years. Marrow transplantation is a reasonable option for adults with progressive thalassemia who have suitable donors.

Bone Marrow Transplantation in Adult Thalassemia

Early trials of allogeneic marrow transplantation for homozygous thalassemia were disappointing in patients older than 16, with four of six patients dying early of graft-versus-host disease-related complications, one patient dying at 9 months of infection due to graft failure, and one dying at 6 years of recurrent thalassemia. Three classes of risk could be identified in analyses of results of transplantation in younger patients using the criteria of degree of hepatomegaly, the presence or absence of portal fibrosis, and a history of adequate or inadequate chelation therapy. Patients for whom all three criteria were adverse constituted a very high risk group (class 3) for marrow transplantation. On the basis of these analyses, a conditioning regimen was designed that yielded superior results for class 3 patients under 17 years of age. Most patients older than 16 years presenting for transplantation have disease characteristics that place them in class 3 and, because of the improved results with the new class 3 regimen in younger patients, a study was designed to treat patients older than 16 years using treatment regimens assigned on the basis of disease class. Twenty patients were treated using this protocol and, with a minimum follow-up of 9 months, there have been three early deaths, one patient has recurrent thalassemia, and 16 patients are alive disease-free. The actuarial probabilities of survival, disease-free survival, and rejection are 0.85, 0.80, and 0.05, respectively, with a survival plateau extending from 6 months to 3 years. Marrow transplantation is a reasonable option for adults with progressive thalassemia who have suitable donors.

Chelation therapy does reverse myocardial deterioration in patients with thalassaemia major

Myocardial function was assessed in 27 patients with transfusion dependent homozygous beta-thalassaemia by multiple gated equilibrium radionuclide angiography. Before the institution of adequate chelation therapy, there was evidence of increasing deterioration in myocardial function with increasing transfusion burden. Out of eight patients with less than 160 transfusions, four cases (50%) had an abnormal cardiac function. Out of five patients with 160–199 transfusion units, four (80%) were abnormal, whilst all five children with 200 transfused units or more had abnormal cardiac function (100%). After periods varying from eight to forty-five months of continuous subcutaneous chelation therapy with desferrioxamine. the average (median) increase in % ejection fraction at rest was 5%. In most patients, deterioration in myocardial function was arrested, and in many reversed. The proportions abnormal in the three transfusion groups, after a period of chelation, were respectively 2/6 (33%). 1/5 (20%). and 6/12 (...

Deaths from acute lead poisoning.

The three fatal cases of acute lead poisoning described show the difficulty experienced in reaching an early diagnosis of lead intoxication. A rapid micromethod is now available for the determination of whole blood lead levels on small samples of blood, using atomic absorption spectrophotometry. Given an increased awareness of acute lead intoxication, the rapid confirmation of the diagnosis by the micromethod, and the early institution of adequate chelation therapy, then fatalities such as those described should not occur in the future.

PRESYMPTOMATIC WILSON'S DISEASE

Presymptomatic Wilson's disease must be diagnosed because the severe consequences of the disease may be prevented by adequate chelation therapy. Seventeen children from five families having members with Wilson's disease have been studied to detect presymptomatic subjects. Seven had clinical Wilson's disease, five were diagnosed as presymptomatic (homozygotes), and five were believed normal or heterozygotes. Kayser-Fleischer rings must be looked for with a slit lamp. They were present in symptomatic but absent in presymptomatic patients. All presymptomatic homozygotes had low serum copper and cæruloplasmin levels, but these estimations could not distinguish them with certainty from heterozygotes. A liver-copper concentration, performed on needle-biopsy samples, over 25 mg. per 100 g. dry weight, confirmed the presymptomatic state. The liver histology may be normal or abnormal, depending on the stage of the disease. Two heterozygotes