Quality of life assessment in hematopoietic stem cell transplantation performed on thalassemia major patients

Although successful hematopoietic stem cell transplantation (HSCT) can offer a cure in thalassemia major, there are only a few and noncomprehensive studies of its effect on the quality of life (QoL), as it is expected to increase the QoL by ending transfusion-related issues. Our objective was to compare the health-related quality of life (HRQoL) of transplanted and nontransplanted thalassemia major patients in a developing country. We have studied the QoL effect of HSCT in consecutively invited 50 nontransplanted and 49 transplanted patients who had received transplants from HLA matched related donors at least two years ago. PedsQL questionnaire was used for the patients under 18?years of age and World Health Organization's WHOQoL-BREF questionnaire for above 18?years of age. Higher QoL was determined in HSCT performed group surveyed in 5-18?years' age group. Detailed analysis marked the profound difference in 8-12 year subgroup, particularly in physical activity questionnaires. QoL scores in HSCT performed adult group are higher than the transfusion-dependent group, especially in physical activity domain. Transplanted adult patients rated their overall health significantly better than patients on conventional therapy. The patients who still have chronic graft versus host disease rated worse compared to those without it. In conclusion, thalassemia major patients who have undergone HSCT at least two years before assessment are not inferior to the transfusion-dependent group with regard to the QoL and have a better QoL than transfusion-dependent patients in some areas. The QoL score is better for school children and adolescents; therefore, we suggest HSCT before primary school. GVHD reduces the QoL significantly and it is obvious that GVHD prevention should be one of the primary goals of post-HSCT follow-up.     

Klebsiella pneumoniae meningitis in thalassemia major patients

Two thalassemia major patients received regular blood transfusion and desferrioxamine chelation, and 1 patient had a splenectomy at 9 years of age. Both patients developed Klebsiella pneumoniae meningitis at age of 27 and 15 years. They died within a short time despite appropriate antibiotic treatment. Klebsiella meningitis may be more common in transfusion-dependent thalassemia patients.     

KLEBSIELLA PNEUMONIAE MENINGITIS IN THALASSEMIA MAJOR PATIENTS

Two thalassemia major patients received regular blood transfusion and desferrioxamine chelation, and 1 patient had a splenectomy at 9 years of age. Both patients developed Klebsiella pneumoniae meningitis at age of 27 and 15 years. They died within a short time despite appropriate antibiotic treatment. Klebsiella meningitis may be more common in transfusion-dependent thalassemia patients.     

���к�ƶѪ��ǰ��ϲ����淶����

??The classification of thalassemia is mainly based on the types of the defective synthesis of the globin chains of adult hemoglobin A and clinical features??the former mainly includes α??β??γ??δ??δβ??etc.??and α or β thalassemia is the most common form of thalassemia??the latter is classified as transfusion-dependent thalassemia and non-transfuion-dependent thalassemia in terms of long-term survival depending on blood transfusion. The diagnostic techniques include screening test and genetic test??the former diagnostic method is mainly based on the morphology of red blood cells and the physical and chemical properities??including routine analysis of blood??red blood cell morphology and hemoglobin electrophoresis??etc.??and the latter is mainly based on PCR technology??including gap-PCR??real-time PCR??gene chip and DNA screening??etc. This paper reviews the classification and laboratory diagnosis techniques in thalassemia??combining comprehesive screening method with technique of genetic diagnosis??which appropriately contributes to the diagnosis of thalassemia.     

Health-Related Quality of Life in Adolescents with Thalassemia

Children and adolescents with thalassemia suffer from chronicity of the disease and its treatment, including transfusion dependence and complications of iron overload. This study aimed to assess the health-related quality of life of adolescents with thalassemia compared with healthy controls. Sixty-four adolescents with thalassemia aged 13 to18 years and their parents were enrolled in this cross-sectional study, as well as their age- and gender-matched those of the healthy controls (64 participants and their parents). The Pediatric Quality of Life Inventory 4.0 Scales (PedsQL 4.0) self-report form was administered to the adolescents in both groups. Parents were also asked to complete the PedsQL 4.0, parent proxy-report form. The self-reported total, psychosocial, and school functioning scores of the thalassemia patients were significantly lower than those of the healthy controls (p = 0.03, 0.04, and <0.001, respectively). The parent-reported psychosocial and school functioning scores of the thalassemia group were also significantly lower than those of the controls (p = 0.03 and 0.003, respectively). Among adolescents with thalassemia, the serum ferritin level and comorbidity were the only variables associated with quality of life scores. This study showed that thalassemia negatively affected quality of life. For a better quality of life, thalassemia patients should be monitored for serum ferritin levels and treated for comorbidity as part of their comprehensive health care.     

Iron overload and iron-chelating therapy in hemoglobin E-beta thalassemia

Whereas hemoglobin (Hb) E-beta thalassemia is recognized as probably the most common serious hemoglobinopathy worldwide, its natural history remains poorly defined. The interaction of hemoglobin E and beta-thalassemia result in a wide spectrum of clinical disorders, some indistinguishable from thalassemia major and some milder and not transfusion-dependent. Partially as a result of this wide range of phenotypes, clear guidelines for approaches to transfusion and to iron-chelating therapy for patients with Hb E-beta thalassemia have not been developed. By contrast, data that have accumulated during the past 10 years in patients with beta-thalassemia permit a quantitative approach to the management of iron overload and provide guidelines for the control of body iron burden in individual patients treated with iron-chelating therapy. These guidelines may be applicable to patients with Hb E-beta thalassemia. Preliminary evidence from our studies of iron loading in affected patients with Hb E-beta thalassemia in Sri Lanka suggest that this disorder may be associated with variable, but accelerated, gastrointestinal iron absorption, and that the iron loading associated with chronic transfusions in patients with Hb E-beta thalassemia is similar to that observed in patients with beta-thalassemia. These data, in the only cohort of patients with Hb E-beta thalassemia to have undergone quantitative assessment of body iron burden, suggest that the principles that guide assessment of iron loading and initiation of chelating therapy in patients with beta-thalassemia may be generally applicable to those with Hb E-beta thalassemia. Further quantitative studies in both nontransfused and transfused patients will be necessary to permit firm conclusions.     

���к�ƶѪ���Ƽ��ۺϹ���

??Thalassemia is a hereditary hemolytic anemia caused by globin peptide gene deficiency. β- thalassemia and α- thalassemia are the most common clinical disorders of β- and α- peptide chain synthesis. Both thalassemia intermedia and major may significantly effect on patient’s growth develop-ment and quality of life??especially in patients with thalassemia major. If not receiving hematopoietic stem cell transplanta-tion??they need rely on life-long blood transfusion and chelation therapy. That leads a high medical costs and a great burden on families??society and the country. Therefore??it is essencial in how to strengthen the management of thalassemic population standardize thalassemic patient’s blood transfusion and iron chelation treatment??effectively to improve the quality life of thalassemic patients and to monitor the population of thalassemia gene carrier??health education and birth intervention.     

Endothelial Dysfunction and Oxidant Status in Pediatric Patients with Hemoglobin E-β Thalassemia

Thalassemia major is characterized by anemia, iron overload, and oxidant damage to major organs, especially the cardiovascular system. Oxidative stress is ultimately involved in endothelial dysfunction, a condition which is evident in adults suffering from various cardiovascular diseases including thalassemia. We investigated endothelial function in pediatric patients with hemoglobin E-β thalassemia (HbE-β thalassemia), who have been exposed to excessive iron and oxidative stress for much shorter period than adults with thalassemia. We recruited 22 blood transfusion-dependent HbE-β thalassemia patients aged 11.8 ± 2.9 years and 20 healthy controls aged 12.1 ± 1.7 years. Oxidant status was determined, and endothelial function was assessed by a forearm blood flow technique. Oxidative stress was increased in the thalassemic patients, as blood glutathione (GSH) and ratios of reduced GSH to GSH disulfide were markedly reduced, and superoxide anion released from blood cells was highly elevated. Oxidative stress response, assessed by γ-glutamylcysteine ligase activity, was increased approximately twofold in thalassemia patients. Basal forearm blood flow was significantly increased in patients compared with controls (7.3 ± 1.8 vs 6.0 ± 1.8 ml/100 ml tissue/min, respectively), whereas forearm vasodilatory response to reactive hyperemia was depressed by 50% in patients compared with controls. Endothelial function is impaired in young thalassemia patients, and impaired endothelial function is associated with oxidant stress.     

Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia

PURPOSE: To determine the prevalence of hypoparathyroidism in transfusion-dependent patients with beta-thalassemia. PATIENTS AND METHODS: A total of 28 transfusion-dependent patients with beta-thalassemia were interviewed, and their serum calcium, phosphate, magnesium, and intact parathyroid hormone levels were checked. Serum ferritin levels were measured to monitor the effect of chelation therapy. Blood urea nitrogen, creatinine, total protein, and albumin were measured in patients with undetectable or low intact parathyroid hormone levels. RESULTS: The prevalence of hypoparathyroidism was 10.7% (3/28). Mean age at diagnosis was 18 years. The serum ferritin levels of patients with hypoparathyroidism were 1,032, 2,102, and 7,680 microg/L. Only one patient had clinical symptoms of hypocalcemia. All three of the patients with hypoparathyroidism had hypogonadism, and 66.7% (2/3) of the patients had insulin-dependent diabetes mellitus. CONCLUSIONS: Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia seems to be accompanied by other endocrinopathies. Serum ferritin may not have been a reliable indicator of iron overload in the three patients with hypoparathyroidism. Severe iron overload would easily explain these multiple endocrinopathies. This pattern is commonly seen in iron-overloaded patients with thalassemia elsewhere.     

Combined therapy with desferrioxamine and deferiprone: a new protocol for iron chelation in thalassemia

Deferiprone (DFO) at the standard daily dose of 75 mg/kg was given to 13 transfusion-dependent patients with thalassemia in whom conventional desferrioxamine (DFX) therapy had proven ineffective and caused adverse side effects. In six patients, serum ferritin and alanine aminotransferase levels decreased significantly and urinary iron excretion increased. In seven patients in whom DFO administration alone was ineffectual, DFX was added at a daily dose of 40 to 50 mg/kg given subcutaneously for 7 to 10 days following transfusion. All patients exhibited a significant decrease in serum ferritin levels and an increase in urinary iron excretion, with alanine aminotransferase levels decreased in four patients. The combined DFX and DFO therapy could represent an effective alternative to conventional DFX therapy not only in nonresponding patients with thalassemia but also, by lowering to less than 25% the DFX dosage, in patients who exhibit important DFX-related side effects.     

Abnormal glucose tolerance in Egyptian beta-thalassemic patients: possible association with genotyping

BACKGROUND: Type 1 diabetes mellitus (DM) is a frequent complication in patients with beta-thalassemia. It is believed to be due to the damage inflicted by iron overload of the pancreatic beta cells. Liver disorders and genetic influences seem to be additional predisposing factors. OBJECTIVE: To study the prevalence of diabetes and impaired glucose tolerance (IGT) in transfusion-dependent Egyptian beta-thalassemic patients and to evaluate the possible role of genotyping in the pathogenesis of diabetes associated with beta-thalassemia. RESEARCH DESIGN and METHODS: A total of 56 transfusion-dependent beta-thalassemic patients aged 10-31 (mean age=15.9 +/- 5.7 yr), 32 males and 24 females, including 48 thalassemia major and eight thalassemia intermedia; compared to 15 age- and sex-matched controls. All were subjected to history and examination, laboratory investigations: complete blood count (CBC), serum ferritin, liver function tests, hepatitis B and C markers, fasting blood glucose, oral glucose tolerance test (OGTT) and fasting C-peptide. Genotyping for 16 mutations was assessed in thalassemic patients with abnormal glucose tolerance. RESULTS: The prevalence of diabetes was 10.4% (5 of 48) and IGT was 14.6% (7 of 48) among thalassemia major, whereas, none of thalassemia intermedia had abnormal glucose tolerance. Fasting C-peptide was lower in beta-thalassemic patients compared to controls (p <0.001); the level was significantly higher in patients complicated by diabetes or IGT compared with other thalassemic patients (p <0.001). Chronic hepatitis C was detected in all patients (100%) with abnormal glucose tolerance. Genotyping showed that IVS II nt 745 was detected in 77.7% of cases with abnormal glucose tolerance. CONCLUSIONS: Abnormal glucose tolerance is common in multiply transfused beta-thalassemia major patients, which could be attributed to progressive and early loss of beta-cell mass, along with persistent insulin resistance. Chronic hepatitis C may play a role in the development of abnormal glucose tolerance. An association between diabetes and genotyping IVS II nt 745 was found. Patients with this particular genotype are advised to check their blood glucose every 6 months to detect early occurrence of diabetes.     

地中海贫血患儿和家长的精神心理及管理

采用艾森克人格问卷、Achenbach儿童行为量表、SF-36的生活质量问卷、Cochrane数据库分析等方法研究发现,重型地中海贫血（地贫）患儿存在社会能力差、焦虑、抑郁、社交退缩和多动等心理行为问题。患儿家长经历震惊、否认、悲伤和愤怒、适应和认知心理变化5个阶段,然后逐渐适应。可通过患者教育、认知疗法、行为疗法、心理弹性培养、聚焦解决模式进行干预治疗地贫患儿及家长的心理行为问题,帮助地贫患儿更好地应对日常生活,履行社会的角色,取得更好的生活质量。     

���к�ƶѪ�����ͼҳ��ľ�����������

??Previous study using Eysenck personality questionnaire??Achenbach children’s behavior checklist??SF-36 quality of life questionnaire??Cochrane Database of Systematic Reviews and other methods found that the children with thalassemia major had psychological behavior problems??such as poor social competence??anxiety??depression??social withdrawal??hyperactivity. Their parents experienced shock??denial??sadness and anger??adaptation and cognitive psychological changes??then gradually adapted over time. Patients education, cognitive therapy??behavioral therapy??mental resilience training??focused coping model of intervention in the treatment of children with thalassemia and their parents’psychological behavior problems can help them better cope with daily life??fulfill the role of society??and achieve better quality of life.     

地中海贫血临床诊治中存在的问题

在中国地中海贫血(地贫)是一种最常见的遗传性溶血性疾病.建立一个在政府主导下的规范严密的地贫预防筛查体系,减少漏诊和误诊的发生,进一步降低和减少重型地贫患者的出生,做好婚前及产前检查极为关键.在现有医疗体制的框架下,建立一个合理完善的医疗保障体系和规范的地贫治疗队伍,提高重型地贫患者的生存质量,是当今面临的重要任务.     

Tolerance induction to deferasirox in a child with transfusion-dependent beta thalassemia

Beta thalassemias are autosomal recessive hemoglobin disorders related to a defect in the beta-globin chain production. Most of the major forms of beta-thalassemia are transfusion dependent leading to iron overload. Today, three iron chelators are available in France. We report the case of a patient suffering from β⁺ major transfusion-dependent thalassemia who presented with severe skin reactions to deferoxamine and deferasirox as well as with agranulocytosis after deferiprone administration. The patient benefited from successful tolerance induction to deferasirox. With the increasing number of children suffering from iron overload, we believe that our protocol can be useful to pediatric hematology teams confronted with multiple iron chelator reactions.     

Blackfan-Diamond disease and malignancy: cause effect relationships?]

The authors report on a 24-year old patient with Blackfan-Diamond syndrome who developed a Hodgkin's disease. This patient became transfusion-dependent at the age of 10, after an initial period of corticosensitivity, and after failure of androgens. He developed hemochromatosis despite from parenteral chelation therapy. He died of infectious complications 4 months after the diagnosis of Hodgkin's lymphoma. A review of the literature shows an increased incidence of malignancies in Blackfan-Diamond syndrome (three cases of leukemia), and in similar disease (thalassemia and sickle cell disease), but not in other patients with hemosiderosis (primitive hemochromatosis, end-stage renal failure under dialysis). Etiopathogenic hypotheses are discussed.     

Successful unmanipulated peripheral blood progenitor cell transplantation from an HLA haploidentical 2-locus-mismatched mother in a thalassemic patient with primary graft failure after transplantation of bone marrow and cord blood from unrelated donors

Abstract:  We report on a boy with β-thalassemia major who developed early graft failure after double-unit unrelated cord blood transplantation, who subsequently received a myeloablative preconditioning regimen using non-T-cell-depleted PBSCT from his HLA-haploidentical 2-loci-mismatched mother. Neutrophil recovery with full donor chimerism was observed at post-transplantation day +11. Furthermore, GVHD was easy to control. The patient was transfusion-independent with complete donor chimerism eight months post-transplant. The result indicated that fetomaternal microchimerism may be an important attribute of a successful transplant. We suggested that a third allo-HSCT may be taken into consideration for patients with transfusion-dependent thalassemia who experience graft failure, even after two previous transplants.     

Use of hydroxyurea and recombinant erythropoietin in management of homozygous beta0 thalassemia

This report describes the sustained response of an Iranian girl with homozygous beta(0) thalassemia (IVS-II-1G-->A) to hydroxyurea (HU) and recombinant erythropoietin (rEPO). Since the start of this regimen 7 years ago, she has been transfusion-independent and her hemoglobin is maintained between 9.5-11.0 gm/dL. She is maintaining consistent growth around the 10th percentile for age and enjoys a good quality of life. She has not had any therapy-related adverse effects. This experience suggests that therapy with HU and rEPO may be useful long-term in some patients with beta thalassemia.     

Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia

OBJECTIVE: To determine the prevalence and risk factors of hypogonadotropic hypogonadism in transfusion-dependent patients with thalassemia. PATIENTS AND METHODS: The authors examined 29 patients with thalassemia major aged 15 years or older. Luteinizing hormone-releasing hormone tests were performed and beta-thalassemia mutations were analyzed by direct sequencing. RESULTS: The prevalence of hypogonadotropic hypogonadism was 72%. Failure of puberty was observed in 5 of 11 (45%) boys and 7 of 18 (39%) girls. Arrested puberty was noted in two boys (18%) and five girls (28%). Ten girls (56%) did not menstruate, two (11%) had regular menstrual cycles, one (6%) had irregular menstrual cycles, and five (28%) developed secondary amenorrhea. Twenty-one and eight patients had the beta 0/beta 0 and beta 0/beta+ hematologic phenotypes, respectively. beta 0-thalassemia mutation alleles involved IVS II-654 (C-T), codons 41/42 (-TCTT), codons 27/28 (+C), and codons 17 (A-T). beta+-thalassemia mutations alleles were -28 (A-G) and HbE (codons 26(GAG-AAG)). Hematologic phenotype (odds ratio, 28.50; P = 0.002) was the only risk factor identified in the logistic regression analysis. CONCLUSIONS: In patients with thalassemia major, genetic differences may influence their susceptibility to hypogonadotropic hypogonadism, possibly as a result of differences in the amounts of blood transfused and/or their vulnerability to free radical damage. The hematologic phenotype is a main determinant of the severity of thalassemia major; hence, it may influence the need for and frequency of blood transfusion and the patient's iron-overload status.