Utility of Holter electrocardiogram in iron-overloaded hemoglobinopathies.

Cardiac arrhythmias are among the leading causes of morbidity and mortality of transfusion-dependent, iron-overloaded beta-thalassemia patients. Routine screening with Holter electrocardiogram has been recommended; however, infrequent electrocardiographic changes limit its clinical usefulness. The purpose of this study was to determine the diagnostic yield of Holter electrocardiogram monitoring and its correlation with patient symptoms and disease status. A retrospective analysis was performed on 27 transfusion-dependent thalassemia patients who underwent cardiac questionnaire and Holter screening yearly, in addition to echocardiogram and quantitative iron-level determination. Four patients had clinically significant arrhythmias detected on Holter screening, while 2 patients developed severe cardiac complications secondary to arrhythmias within 1 year of follow-up of normal Holter screening. Early detection of cardiac events among transfusion-dependent thalassemia patients with Holter electrocardiography is not clinically effective. Other screening modalities, including the transtelephonic event recorder, should be evaluated in arrhythmia surveillance.

Treatment of hepatitis C virus infection in thalassemia.

Treatment of hepatitis C virus (HCV) in the general population has improved over the last decade. Patients treated with peginterferon alfa (PegIFN) and ribavirin (RBV) combination therapy demonstrate overall 50-55% sustained viral response (SVR) with rates as high as 80% in patients with genotypes 2 and 3. Because RBV induces hemolysis and subsequently increases blood transfusion requirements, combination therapy has been considered contraindicated for hemoglobinopathies. This report reviews the response to interferon alfa and RBV (IFN/RBV) and PegIFN/RBV combination therapies in patients treated in the Northern California Comprehensive Thalassemia Center. A total of six thalassemia major patients were treated with IFN/RBV (n = 5; age: 4-38 years) or with PegIFN/RBV (n = 1; age: 26 years). Quantitative HCV RNA polymerase chain reaction and liver iron level assessment were completed. Transfusion volumes were obtained from patients' medical records. On IFN/RBV combination, four of five patients demonstrated SVR. The one patient on PegIFN/RBV showed end-treatment viral response after 6 months of therapy (genotype 3), but subsequently relapsed. Liver iron pretreatment level ranged from 0.2 to 22 mg/g dry weight, with a mean +/- SD of 7.9 +/- 7.7. Transfusion requirement increased by a median of 43.5% (range: 32-137%). Five of the six patients had liver iron measurements within 1 year following completion of treatment, with quantitative liver iron increasing in two patients by 2.5 mg/g dry weight, decreasing in two patients by 3 and 14 mg/g dry weight, and remaining unchanged in one patient. All patients were able to complete combination therapy, although dose reductions were required. Patients with thalassemia and high iron overload can obtain SVR after combination therapy with rates similar to those in the general population and without significant complications. Although transfusion requirements increased in most patients, iron burden was not necessarily increased.

Quality of life in patients with thalassemia intermedia compared to thalassemia major.

The impact of thalassemia major and thalassemia intermedia and their associated complications on quality of life (QOL) is largely unknown. Determining the degree of health impairment as perceived by the patient is essential information needed to recommend suitable therapy. The objective of this study was to evaluate QOL in transfusion-independent patients with thalassemia (non-Tx) compared with that in transfused patients (Tx) and to identify the factors that affect QOL in thalassemia. A convenient sample of 48 thalassemia patients (29 Tx and 19 non-Tx) with mean age of 14.6 years (SD = 7.5 years) were selected during a comprehensive visit to complete a Dartmouth Primary Care Cooperative Information Chart System (COOP) questionnaire. Patients rated QOL from excellent (1) to poor (5) on five dimensions of health status. Scores of 4 or 5 represent major limitations. These results were augmented by a brief medical history and chart review. Forty-one percent of Tx patients and 47% of non-Tx patients reported severe impairments in 1-6 and 1-2 domains, respectively. The most commonly reported affected domains were feelings such as anxiety, depression, and concern of overall health status or indications of recent deterioration in health. In contrast with previous beliefs, transfusion-independent thalassemia patients also suffer serious impairment in QOL. Presented data suggest that all patients with thalassemia undergo QOL assessment so that interventions focused on affected domains can be implemented.

Outcomes of preimplantation genetic diagnosis therapy in treatment of beta-thalassemia: A retrospective analysis.

Thalassemia is one of the most common single-gene disorders that can be cured by hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)-identical sibling donor. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be used to select an unaffected, HLA-identical embryo. In brief, this procedure requires in vitro fertilization, oocyte retrieval, fertilization, and blastomere biopsy for identification of unaffected HLA-identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. The objective of this study was to determine the outcomes of families using PGD therapy for cure of beta-thalassemia and to review the limitations of PGD therapy. Families affected with beta-thalassemia who attempted PGD therapy were retrospectively identified and reviewed for indication, attempted cycles, successful pregnancy, and transplantation outcomes. Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included six cases of beta-thalassemia major and two cases of transfusion-dependent hemoglobin E-beta-thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from one to four attempts per family. Following successful identification of HLA-identical cells, two pregnancies occurred, of which one resulted in engraftment of a beta-thalassemia child. PGD therapy offers the possibility of recruiting a suitable donor for HCT, yet is limited by financial cost due to labor-intensive techniques, low probability of obtaining an HLA-matched unaffected embryo, variable implantation capacity, and significant emotional impact. Improvements in PGD therapy's efficacy and cost will make this a more viable option for affected families.

A simple model to assess and improve adherence to iron chelation therapy with deferoxamine in patients with thalassemia.

Adherence to deferoxamine (DFO) is vital for the long-term survival of patients with thalassemia; however, currently no measure exists to quantify adherence directly. In this study, 90 patients with thalassemia major underwent liver iron concentration (LIC) assessment by SQUID biosusceptometer, were asked to rate their adherence to DFO using a Numerical Likert Scale (NLS), and were educated about complications of iron overload. Of 38% (n = 28) of patients who rated themselves as very compliant, 19 had elevated LIC related to inadequate dosing of DFO and nine reported nonadherence in the past. Adherence improved after counseling and LIC decreased by 25% (7-60%) in eight previously noncompliant patients who returned for subsequent LIC over 15 months. In conclusion, the NLS seems to be a simple but reliable tool to assess patients' adherence to DFO. Education and frequent noninvasive LIC assessments can improve adherence and iron burden. Elevated LIC does not necessarily reflect concurrent noncompliance; however, it can be an indication of nonadherence in the past.