Survival in medically treated patients with homozygous beta-thalassemia.
01 Sep 1994-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 331, Iss: 9, pp 574-578
TL;DR: Univariate analysis demonstrated that factors affecting cardiac disease-free survival were age at the start of chelation therapy and life-table analysis to estimate freedom from cardiac disease over time.
Abstract: Background The prognosis of patients with homozygous β-thalassemia (thalassemia major) has been improved by transfusion and iron-chelation therapy. We analyzed outcome and prognostic factors among patients receiving transfusions and chelation therapy who had reached the age at which iron-induced cardiac disease, the most common cause of death, usually occurs. Methods Using the duration of life without the need for either inotropic or antiarrhythmic drugs as a measure of survival without cardiac disease, we studied 97 patients born before 1976 who were treated with regular transfusions and chelation therapy. We used Cox proportional-hazards analysis to assess the effect of prognostic factors and life-table analysis to estimate freedom from cardiac disease over time. Results Of the 97 patients, 59 (61 percent) had no cardiac disease; 36 (37 percent) had cardiac disease, and 18 of them had died. Univariate analysis demonstrated that factors affecting cardiac disease-free survival were age at the start of che...
Citations
More filters
TL;DR: Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment, and early intensification of iron chelation therapy should reduce mortality from this reversible cardiomyopathy.
Abstract: Aims To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops.Methods and Results We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0(.)93, P <0(.)0001). Inter-study cardiac reproducibility was 5(.)0%. As myocardial iron increased. there was a progressive decline in ejection fraction (r=0(.)61, P <0(.)001). All patients with ventricular dysfunction had a myocardial T2* of < 20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0(.)79, P <0(.)002).Conclusions Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique. should reduce mortality from this reversible cardiomyopathy. (C) 2001 The European Society of Cardiology.
1,497 citations
Cites background from "Survival in medically treated patie..."
...Cardiac failure secondary to transfusional iron overload remains the commonest cause of death in patients with thalassaemia major[1, 2 ]....
[...]
TL;DR: It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency.
Abstract: Despite major advances in our understanding of the molecular pathology, pathophysiology, and control and management of the inherited disorders of haemoglobin, thousands of infants and children with these diseases are dying through lack of appropriate medical care. This problem will undoubtedly increase over the next 20 years because, as the result of a reduction in childhood mortality due to infection and malnutrition, more babies with haemoglobin disorders will survive to present for treatment. Although WHO and various voluntary agencies have tried to disseminate information about these diseases, they are rarely mentioned as being sufficiently important to be included in setting health care priorities for the future. It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency.
1,121 citations
Cites background from "Survival in medically treated patie..."
...With adequate transfusion and the administration of the chelating agent, desferrioxamine, children may grow and develop well and survive into adult life (11, 12 )....
[...]
TL;DR: Survival and complication-free survival of patients with thalassemia major continue to improve, especially for female patients born shortly before or after the availability of iron chelation.
Abstract: BACKGROUND AND OBJECTIVES: Seven Italian centers reported data on survival, causes of death and appearance of complications in patients with thalassemia major. The interactions between gender, birth cohort, complications, and ferritin on survival and complications were analyzed. DESIGN AND METHODS: Survival after the first decade was studied for 977 patients born since 1960 whereas survival since birth and complication appearance was studied for the 720 patients born after 1970. Better survival was demonstrated for patients born in more recent years (p<0.00005) and for females (p=0.0003); 68% of the patients are alive at the age of 35 years. In the entire population 67% of the deaths were due to heart disease. RESULTS: There was a significant association between birth cohort and complication-free survival (p<0.0005). The prevalence of complications was: heart failure 6.8%, arrhythmia 5.7%, hypogonadism 54.7%, hypothyroidism 10.8%, diabetes 6.4%, HIV infection 1.7%, and thrombosis 1.1%. Lower ferritin levels were associated with a lower probability of heart failure (hazard ratio =3.35, p<0.005) and with prolonged survival (hazard ratio = 2.45, p<0.005), using a cut-off as low as 1,000 ng/mL. INTERPRETATION AND CONCLUSIONS: Survival and complication-free survival of patients with thalassemia major continue to improve, especially for female patients born shortly before or after the availability of iron chelation.
1,064 citations
Cites background from "Survival in medically treated patie..."
...demonstrated a better prognosis for survival without cardiac disease in transfused patients whose ferritin concentrations remained below 2,500 ng/mL.(27) In our population, a lower ferritin concentration predicted longer survival, and reduced risk of cardiac complications and of hypogonadism, both using the ferritin values directly, and when grouped to, below or above a threshold as low as 1,000...
[...]
TL;DR: The toxicity of this agent mandates a careful evaluation of the balance between risk and benefit of deferiprone in patients with thalassemia, in most of whom long-term deferoxamine is safe and efficacious therapy.
1,050 citations
TL;DR: A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older, and found it to be a promising once-daily oral therapy for the treatment of transfusional iron overload.
660 citations
References
More filters
TL;DR: Overall survival from birth for patients born in 1970-74 was 97.4% at 10 years, and 94.8% at 15 years, while the most common cause of death was heart disease, followed by infection, liver disease, and malignancy.
621 citations
TL;DR: It is concluded that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.
Abstract: We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.
587 citations
TL;DR: Brahms discusses the legal aspects of confidentiality and disclosure of HIV status to various third parties, and the legal liability and legal claims of HIV infected persons.
551 citations
TL;DR: An immunoradiometric assay for human ferritin has been developed and it is thought that the serum Ferritin concentration may reflect the iron stores of the body.
Abstract: An immunoradiometric assay for human ferritin has been developed. Concentrations of ferritin in the serum of male and female controls and patients with iron deficiency and iron overload were measured.Male controls were found to have a significantly higher mean concentration of serum ferritin than females. Patients with iron deficiency had significantly lower levels than normals of either sex and patients with iron overload had greatly elevated serum ferritin concentrations. It is thought that the serum ferritin concentration may reflect the iron stores of the body.
546 citations
TL;DR: Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond-Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both, and detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more.
Abstract: Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond-Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both. Detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more. Four patients with visual loss had optic neuropathy, with a marked decrease in acuity, loss of color vision, and delayed visual evoked potentials. Five asymptomatic patients had changes in the pigment of the retinal epithelium. The hearing loss was characterized by a high-frequency sensorineural deficit, which necessitated hearing aids in six patients. When deferoxamine was stopped, recovery of vision was complete in 2 patients and partial in 2, and in 22 patients with abnormal audiograms, reversal of the hearing deficit was complete in 4 and partial in 1. An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight. Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P less than 0.001, less than 0.006, and less than 0.04, respectively). The data implicate high-dose deferoxamine as a central factor in the pathogenesis of the neurotoxicity. We strongly recommend careful regulation of the deferoxamine dosage and serial audiovisual monitoring in all patients receiving the drug.
393 citations