Effect of drug use calendar on adherence to iron chelation therapy in young thalassemia patients.

Background: Regular blood transfusions in thalassemia patients can lead to severe complications and iron chelation therapy is required as a treatment. Thalassemia is common in Thailand and the drugs used in iron chelation therapy are deferoxamine and deferiprone. Adherence to the therapy is a key factor for treatment success. Objective: To assess the impact of a drug use calendar on deferiprone and deferoxamine adherence in young thalassemia patients. Methods: A total of 86 young thalassemia outpatients at a Thai tertiary care hospital were recruited into the study. Patients were stratified into two groups based on self-assessment of adherence using a visual analogue scale. One group (n=41) was given a calendar with the schedule of drug use in addition to counselling as standard pharmaceutical care. The second group (n=45) only received the counselling. Adherence to iron chelation therapy was assessed by deferiprone pill or deferoxamine vial counts on six visits (V1 to V6) and results were compared between visits and groups using a multilevel linear regression model. Change in serum ferritin levels after 6 visits (n = 81) were compared using a linear regression model. Results: Adherence significantly increased in both the calendar and non-calendar groups for deferiprone mono- and combination-therapy and for deferoxamine monotherapy. In the calendar groups, average adherence increased by between 2.05 and 5.66% per visit compared to increases of 0.31 to3.92% per visit in the non-calendar groups. A significant difference in the increase in adherence per visit between the calendar and non-calendar groups was only observed for deferiprone monotherapy (3.03% SEM = 0.49vs 1.42% SEM =0.49, respectively, P-value = 0.0078). The serum ferritin level decreased in the calendar group by 20.25ng/mL (SEM = 23.80) and increased in the non-calendar group by 59.63 ng/mL (SEM = 23.01, P-value = 0.0147). Conclusion: Provision of a drug use calendar improved adherence to deferoxamine and deferiprone and decreased serum ferritin levels in young Thai thalassemia patients over the improvements obtained from standard counselling.

Effect of drug use calendar on adherence to iron chelation therapy in young thalassemia patients

Background: Regular blood transfusions in thalassemia patients can lead to severe complications and iron chelation therapy is required as a treatment. Thalassemia is common in Thailand and the drugs used in iron chelation therapy are deferoxamine and deferiprone. Adherence to the therapy is a key factor for treatment success. Objective: To assess the impact of a drug use calendar on deferiprone and deferoxamine adherence in young thalassemia patients. Methods: A total of 86 young thalassemia outpatients at a Thai tertiary care hospital were recruited into the study. Patients were stratified into two groups based on self-assessment of adherence using a visual analogue scale. One group (n=41) was given a calendar with the schedule of drug use in addition to counselling as standard pharmaceutical care. The second group (n=45) only received the counselling. Adherence to iron chelation therapy was assessed by deferiprone pill or deferoxamine vial counts on six visits (V1 to V6) and results were compared between visits and groups using a multilevel linear regression model. Change in serum ferritin levels after 6 visits (n = 81) were compared using a linear regression model. Results: Adherence significantly increased in both the calendar and non-calendar groups for deferiprone mono- and combination-therapy and for deferoxamine monotherapy. In the calendar groups, average adherence increased by between 2.05 and 5.66% per visit compared to increases of 0.31 to3.92% per visit in the non-calendar groups. A significant difference in the increase in adherence per visit between the calendar and non-calendar groups was only observed for deferiprone monotherapy (3.03% SEM = 0.49vs 1.42% SEM =0.49, respectively, P-value = 0.0078). The serum ferritin level decreased in the calendar group by 20.25ng/mL (SEM = 23.80) and increased in the non-calendar group by 59.63 ng/mL (SEM = 23.01, P-value = 0.0147). (AU)

The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?

INTRODUCTION: Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. METHODS: This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. RESULTS: One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. CONCLUSIONS: The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.

A Mobile App, KhunLook, to Support Thai Parents and Caregivers With Child Health Supervision: Development, Validation, and Acceptability Study.

BACKGROUND: In Thailand, children born in government hospitals receive a maternal and child health handbook (MCHH). However, when a new MCHH edition is released, those with the previous editions do not have access to the updated information. A mobile app is an appealing platform to fill this gap. We developed a mobile app called "KhunLook" as an interactive electronic MCHH intended to assist parents in child health supervision. OBJECTIVE: This study describes the user requirements and development of the KhunLook mobile app, validity of parents' growth assessments, and parents' evaluation of feasibility and acceptability of the app. METHODS: Phase 1 was a qualitative study using individual interviews. The interview data were used to revise the prototype. In phase 2, parents were randomly assigned to assess their children's growth with the app or the MCHH. The outcomes were compared to those of the physician's assessment, and congruence was determined. In phase 3, parents evaluated the feasibility and acceptability of the app in comparison to the MCHH through a web-based survey. RESULTS: Four health care providers and 8 parents participated in phase 1. Two themes were identified: (1) the mobile app potentially counters parents' infrequent use of the MCHH with accuracy, attractiveness, convenience, and simplicity, and (2) health supervision needs to be standard, up-to-date, and understandable. KhunLook was publicly launched with a family page and 7 key features: growth and nutrition, development, immunizations, oral health, reminders for the next appointment, memories, and health advice. In phase 2, 56 parents participated in the growth parameter assessments; 34 were in the App group and 22 in the MCHH group. The outcomes of the growth parameter assessments between parents and physicians in both the App and MCHH groups were not significantly different. The congruence proportions were higher in the App group for weight and head circumference, but the differences were not statistically significant. In phase 3, 356 parents from all over Thailand participated in a web-based survey. Parents rated the app feasibility as "very easy to easy" to use at higher proportions than the MCHH in all health assessment domains (growth, development, and immunizations) and ease-of-use domains with statistical significance (P<.001). The KhunLook app received a significantly higher mean score (8.59/10) than the MCHH (7.6/10) (P<.001). Most parents (317/356, 89.0%) preferred the app over MCHH. Further, 93.5% (333/356) of the parents stated that they would continue to use the app and 96.9% (345/356) would recommend others to use it. CONCLUSIONS: KhunLook, a Thai mobile app for child health supervision, was developed, validated for growth assessments, and was well accepted for ease-of-use by parents. Further studies should be conducted with a large scale of users, and the impact of this app on health behaviors and health outcomes must be evaluated.

Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using a Novel Conditioning Regimen.

Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors.

Cellular adaptation mediated through Nrf2-induced glutamate cysteine ligase up-regulation against oxidative stress caused by iron overload in ß-thalassemia/HbE patients.

Oxidative stress caused as a result of iron overload is implicated in clinical manifestation of beta-thalassemia/haemoglobin E (ß-Thal/HbE). In this study, we investigated the cellular adaptation against oxidative stress in ß-Thal/HbE patients. Twenty-four paediatric ß-Thal/HbE patients and 22 healthy controls were recruited in the study. Blood samples from patients exhibited iron overload, elevation of lipid peroxidation, and marked diminution in the reduced glutathione (GSH) level. However, expression of glutamate-cysteine ligase catalytic (GCLC) subunit, a key enzyme in GSH biosynthesis, was up-regulated when compared with that in controls. GCLC protein levels were correlated with serum iron. There was an enhanced binding activity of the oligonucleotide probe for Nrf2-driven antioxidant response element (ARE) to nuclear protein from blood mononuclear cells of thalassemia subjects. In conclusion, ß-Thal/HbE patients exhibit elevated plasma levels of GCLC expression and Nrf2-ARE binding activity, which may account for their adaptive survival response to oxidative stress.

Presentation of Compound Heterozygous Hemoglobin Constant Spring and Hemoglobin Pakse in Neonates.

BACKGROUND: Mutations causing α thalassemia are divided into deletion and nondeletion groups. In the nondeletion group, hemoglobin constant spring (Hb CS) and hemoglobin Pakse (Hb Pakse) are both caused by a termination codon mutation leading to elongation of the α2 globin gene. In the case of Hb CS, the mutation is TAA→CAA, whereas the mutation causing Hb Pakse is TAA→TAT. Clinical hematologic phenotypes are not significantly different. It is important to identify compound heterozygotes for purposes of genetic counseling. METHODS: We report 5 neonates with compound heterozygous Hb CS/Hb Pakse mutations with respect to clinical courses, hematologic profiles, and management. RESULTS: Among 5 cases (3 male babies and 2 female babies) with mean birth weight 2982 g (range, 2660 to 3440 g), 3 were diagnosed as compound heterozygous Hb CS/Hb Pakse, 1 as homozygous Hb E with compound heterozygous Hb CS/Hb Pakse, and 1 as heterozygous Hb E with compound heterozygous Hb CS/Hb Pakse. Clinical manifestations included fetal anemia (1 case), neonatal hyperbilirubinemia (5), neonatal anemia (2), hepatosplenomegaly (1), and cholestatic jaundice (1). Three cases required a single phototherapy; 2 cases needed double phototherapy for treatment of severe hyperbilirubinemia. During the first few months of life, all cases had mild anemia, slightly low mean corpuscular volume, wide red cell distribution width, and low red cell counts. At 1 to 3 years of age, all patients still had mild microcytic hypochromic anemia with Hb levels around 10 g/dL, increased reticulocyte count, and wide red cell distribution width. CONCLUSIONS: Misdiagnosis of Hb Pakse could occur via Hb typing using Hb electrophoresis, because the band comigrates with that of Hb CS. DNA study is the definitive method for diagnosis.

Mitochondrial ferritin expression in erythroid cells from patients with alpha-thalassaemia.

BACKGROUND: Patients with thalassaemia who received regular transfusions had increased iron accumulation, leading to iron overload, which was associated with oxidative stress. Mitochondrial ferritin, encoded by the FTMT gene is an iron-storage protein in the mitochondria. The aim of this work was to investigate the expression levels of FTMT in the reticulocytes of patients with alpha-thalassaemia who were regularly transfused and rarely transfused compared with healthy controls and to evaluate the relationships of the levels of FTMT mRNA with malondialdehyde (MDA) and ferritin in these patients. METHODS: The levels of FTMT mRNA in the reticulocytes of patients (30 regularly transfused and 30 rarely transfused) and 30 healthy individuals were assessed by quantitative reverse transcription-polymerase chain reaction. The levels of ferritin and MDA were analysed by ELISA and by a thiobarbituric acid reactive substance assay, respectively. RESULTS: The levels of FTMT mRNA, ferritin and MDA in both groups of patients were significantly increased compared with those in the healthy controls. In addition, the levels of FTMT mRNA, ferritin and MDA in the regularly transfused patients were significantly higher than those in the rarely transfused patients. Furthermore, the relative expression levels of FTMT in patients correlated with those of MDA and ferritin. CONCLUSION: These results suggest that the elevation of expression levels of FTMT in the reticulocytes of patients with alpha-thalassaemia may be associated with iron loading and oxidative stress.

Clinical Course of Homozygous Hemoglobin Constant Spring in Pediatric Patients.

BACKGROUND: Hemoglobin (Hb) Constant Spring is an alpha-globin gene variant due to a mutation of the stop codon resulting in the elongation of the encoded polypeptide from 141 to 172 amino acid residues. Patients with homozygous Hb Constant Spring are usually mildly anemic. METHODS: We retrospectively describe clinical manifestations, diagnosis, laboratory investigations, treatment, and associated findings in pediatric patients with homozygous Hb Constant Spring followed-up at Srinagarind Hospital. RESULTS: Sixteen pediatric cases (5 males and 11 females) were diagnosed in utero (N=6) or postnatal (n=10). Eleven cases were diagnosed with homozygous Hb Constant Spring, 4 with homozygous Hb Constant Spring with heterozygous Hb E, and 1 with homozygous Hb Constant Spring with homozygous Hb E. Three cases were delivered preterm. Six patients had low birth weights. Clinical manifestations included fetal anemia in 6 cases, hepatomegaly in 1 case, hepatosplenomegaly in 2 cases, splenomegaly in 1 case. Twelve cases exhibited early neonatal jaundice, 9 of which required phototherapy. Six cases received red cell transfusions; 1 (3), >1 (3). After the first few months of life, almost all patients had mild microcytic hypochromic anemia and an increased reticulocyte count with a wide red cell distribution (RDW), but no longer required red cell transfusion. At 1 to 2 years of age, some patients still had mild microcytic hypochromic anemia and some had normocytic hypochromic anemia with Hb around 10 g/dL, increased reticulocyte count and wide RDW. Associated findings included hypothyroidism (2), congenital heart diseases (4), genitourinary abnormalities (3), gastrointestinal abnormalities (2), and developmental delay (1). SUMMARY: Pediatric patients with homozygous Hb Constant Spring developed severe anemia in utero and up to the age of 2 to 3 months postnatal, requiring blood transfusions. Subsequently, their anemia was mild with no evidence of hepatosplenomegaly. Their Hb level was above 9 g/dL with hypochromic microcytic blood pictures as well as wide RDW. Blood transfusions have not been necessary since then.

Effect of health education on severe thalassemia prevention and control in communities in Cambodia.

BACKGROUND: Severe thalassemia diseases are a major health problem in Southeast Asia. In Cambodia, there has never been a significant program for prevention or control of severe thalassemia. We, therefore, studied the effect of a health education program on severe thalassemia prevention and control in Phnom Penh, Cambodia. METHODS: A quasi-experimental study in several communities around Phnom Penh was done. The respective intervention and control group comprised 124 and 117 people, between 18 and 40 years of age, male and female. Pre- and post-tests using a validated and reliable questionnaire were performed in the intervention group and one test was done in the control group. A health education program was organized to give important information to the intervention group and, at the end of the process, to the control group. The outcomes were evaluations of their knowledge and attitude vis-à-vis severe thalassemia prevention and control, and participating in thalassemia screening. RESULTS: Among participants in the intervention group, 105 (84.7%) considered undergoing blood screening vs. 65 (55.6%) in the control group (p-value < 0.001). In the intervention group, the respective mean scores for knowledge and attitude to a prevention and control program for severe thalassemia before and after health education were 2.6 VS 6.5 (p-value < 0.001) and 4.6 VS 6.5 (p-value < 0.001). CONCLUSIONS: The intention to undergo screening was significantly higher in the intervention group than the control group. Knowledge and attitude towards prevention and control of severe thalassemia was significantly improved in the intervention group. Health education clearly heightens awareness and improves consideration of screening for prevention and control of severe thalassemia.

Elevations of Thrombotic Biomarkers in Hemoglobin H Disease.

BACKGROUND: Thalassemia is a group of hereditary hemoglobinopathies caused by decreased or absent synthesis of α and/or ß globin chains. Studies have shown that hypercoagulability and thrombosis are common clinical symptoms in ß-thalassemia, especially ß-thalassemia intermedia, but little is known about in α-thalassemia. This study aims to examine phosphatidylserine (PS) levels, platelet activation, and coagulation markers in splenectomized (S) and nonsplenectomy (NS) patients with hemoglobin (Hb) H disease. METHODS: The NS group comprised 20 patients (median age 15.0 years, range, 14-16.5 years), and the S group consisted of 11 patients (median age 16.4 years, range, 14-19.9 years) with Hb H disease; the control group consisted of 20 normal subjects. Hematological parameters were collected. Flow cytometry was used to measure PS exposure on red blood cells. The levels of intercellular adhesive molecule (ICAM)-1, tumor necrosis factor α (TNFα), ß-thromboglobulin (TG) and prothrombin fragment 1 + 2 (F1.2) were determined using ELISA test kits. RESULTS: Significant increases in the levels of PS, ICAM-1, TNFα, ß-TG, and F1.2 were observed in both patient groups compared to normal controls (p < 0.01). CONCLUSION: This observation indicates blood coagulation, endothelial injury, chronic low-grade inflammation, platelet activation, and thrombin generation are present in Hb H disease; these findings merit further assessment in a larger prospective cohort to establish possible links with thrombotic manifestations.

Fetal Anemia Causing Hydrops Fetalis From an Alpha-Globin Variant: Homozygous Hemoglobin Constant Spring.

BACKGROUND: Fetal anemia is often assumed to be due to red cell alloimmunization and Parvovirus infection, and can lead to hydrops fetalis and death in utero. Other causes, such as mutations of hemoglobin alpha, are less commonly considered. METHODS: We report 7 cases with fetal anemia causing hydrops fetalis. Serial Doppler ultrasound for measurement peak systolic velocity (PSV) of middle cerebral artery (MCA) was used for evaluation of fetal anemia. Fetal anemia is suggested if the MCA/PSV ratio is >1.5 multiple of median. Cordocentesis was performed subsequently to find the cause of fetal anemia and check fetal hemoglobin for consideration of intrauterine infusion. Investigations for fetal anemia include complete blood count, blood morphology, and blood group of mother and fetus, reticulocyte counts, red cell indices, screening for thalassemia, hemoglobin typing, acid elution test, parvovirus B 19 serology, and TORCH titer (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, and syphilis). Intrauterine infusion, using irradiated prestorage filtered red cell with hematocrit level of 80%, is indicated if fetal hemoglobin is <10 g/dL. RESULT: Seven cases with fetal anemia were prenatally diagnosed from gestational ages 20 to 34 weeks. Initial hematocrit in these cases varied from 9% to 17.2%. In each case, causes of anemia were determined using the investigations listed above. All cases underwent uneventfully up to 3 intrauterine transfusions. DNA study for thalassemia demonstrated homozygous Constant Spring (CS) in 5 cases, homozygous CS with heterozygous E in 1 case, and compound heterozygous CS and Pakse in 1 case. The perinatal outcomes were normal term in 5 cases, preterm in 2 cases. Low birth weight was determined in 2 cases. The screening for thalassemia major, including the osmotic fragility and dichlorophenol indophenol precipitation test (DCIP), is not helpful for detecting hemoglobin variants such as Constant Spring or Pakse. SUMMARY: This study emphasizes homozygous Constant Spring and compound heterozygous CS and Pakse as a cause of hydrops fetalis. Proper management for the fetus after diagnosis can lead to a good fetal outcome. Prevention control programs should include screening of parents for the heterozygous state.

Epidemiologic study of major complications in adolescent and adult patients with thalassemia in Northeastern Thailand: the E-SAAN study phase I.

INTRODUCTION: Thalassemia-related complications are one of the main factors that increase morbidity and mortality in aging patients with thalassemia. This study was aimed to report the prevalence and clinical risk factors for the complications in thalassemia. METHODS: A multi-center prospective cohort study was conducted in patients with thalassemia aged ≥10 years old. Thalassemia-related complications were heart failure, pulmonary hypertension, extramedullary hematopoiesis, endocrine disorders, infections, thrombosis and leg ulcers. The clinical parameters significantly associated with the complications were analyzed by logistic regression methods. RESULTS: The prevalence of thalassemia-related complications was 60.5% in patients with transfusion-dependent thalassemia (TDT) and 43% in patients with non-transfusion-dependent thalassemia (NTDT). Splenectomy was statistically associated with complications in both TDT and NTDT patients (adjusted odds ratio (AOR) = 7.4, p-value = 0.0001 and AOR = 2.6, p-value = 0.001). Age ≥50 years old (AOR = 2.9, p-value = 0.04) and female gender (AOR = 0.5, p-value = 0.03) were statistically associated with the complications in patients with NTDT. CONCLUSION: Nearly half of the patients in this cohort had disease-related complications. Splenectomy and advanced age were important factors for complication involvement. Early screening for the complications may reduce the morbidity and mortality in patients with thalassemia.

Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: A multicenter study based on real-world data.

Prevalence of cardiac and liver iron overload in patients with thalassemia in real-world practice may vary among different regions especially in the era of widely-used iron chelation therapy. The aim of this study was to determine the prevalence of cardiac and liver iron overload in and the management patterns of patients with thalassemia in real-world practice in Thailand. We established a multicenter registry for patients with thalassemia who underwent magnetic resonance imaging (MRI) as part of their clinical evaluation. All enrolled patients underwent cardiac and liver MRI for assessment of iron overload. There were a total of 405 patients enrolled in this study. The mean age of patients was 18.8±12.5years and 46.7% were male. Two hundred ninety-six (73.1%) of patients received regular blood transfusion. Prevalence of cardiac iron overload (CIO) and liver iron overload (LIO) was 5.2% and 56.8%, respectively. Independent predictors for iron overload from laboratory information were serum ferritin and transaminase for both CIO and LIO. Serum ferritin can be used as a screening tool to rule-out CIO and to diagnose LIO. Iron chelation therapy was given in 74.6%; 15.3% as a combination therapy.

A Clinical Risk Score for Predicting Paraspinal Extramedullary Hematopoiesis in Patients with Thalassemia: The KKU-EMH Score.

Background: Paraspinal extramedullary hematopoiesis (EMH) is uncommon, but it is one of major complications of increased morbidity in patients with thalassemia. Objective: To develop a clinical risk score for predicting paraspinal extramedullary hematopoiesis in patients with thalassemia. Material and Method: A retrospective study was conducted in adult patients with thalassemia at Srinagarind Hospital, Khon Kaen University (KKU) and Udonthani Hospital, Thailand. Paraspinal EMH was defined as radiologic evidence of EMH foci with or without symptoms. The clinical parameters significantly associated with EMH were entered into the logistic regression model. The risk score was derived from the final model's coefficients. A receiver-operating characteristic (ROC) curve was constructed to determine the area under the ROC curve and the cut-off point. Results: The KKU-EMH score included: 1) age greater than 25 year (2 points) and 2) thalassemic facie (3 points). Using the cut-off of 5 points, the score showed good discrimination with an area under the ROC curve of 0.83 (95% CI 0.76 to 0.90). Conclusion: Advanced age and thalassemic facie are independent risk factors for paraspinal EMH in patients with thalassemia. The KKU-EMH score is a practical score. It can be used as a screening tool for paraspinal EMH in patients with ß-thalassemia.

Trends in Survival of Childhood Cancers in a University Hospital, Northeast Thailand, 19932012.

BACKGROUND: In Thailand, a national treatment protocol for childhood leukemia and lymphoma (LL) was implemented in 2006. Access to treatment has also improved with the National Health Security system. Since these innovations, survival of childhood LL has not been fully described. MATERIALS AND METHODS: Trends and survival of children under 15 with childhood cancers diagnosed between 1993 and 2012 were investigated using the hospitalbased data from the Khon Kaen Cancer Registry, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. Childhood cancers were classified into 12 diagnostic groups, according to the ICCC based on the histology of the cancer. Survival rates were described by period, depending on the treatment protocol. For leukemias and lymphomas, survival was assessed for 3 periods (199399, 20005, 200612) while for solid tumors it was for 2 periods (before and after 2000). The impacts of sex, age, use of the national protocol, and catchment area on leukemia and lymphoma were evaluated. Overall survival was calculated using the KaplanMeier method while the Cox proportional hazard model was used for multivariate analysis. Trends were calculated using the R program. RESULTS: A total of 2,343 childhood cancer cases were included. Survival for acute lymphoblastic leukemia (ALL) from 19939, 20005, and 200612 improved significantly (43.7%, 64.6%, and 69.9%). This was to a lesser extent true for acute nonlymphoblastic leukemia (ANLL) (28.1%, 42.0%, and 42.2%). Survival of nonHodgkin lymphoma (NHL) also improved significantly (44%, 65.5%, and 86.8%) but not for Hodgkin disease (HD) (30.1%, 66.1%, and 70.6%). According to multivariate analysis, significant risk factors associated with poor survival in the ALL group were age under 1 and over 10 years, while not using the national protocol had hazard ratios (HR) of 1.6, 1.3, and 2.3 respectively. In NHL, only nonuse of national protocols was a risk factor (HR 3.9). In ANLL and HD, none of the factors influenced survival. Survival of solid tumors (liver tumors, retinoblastomas) were significantly increased compared to after and before 2000 while survival for CNS tumors, neuroblastoma and bone tumors was not changed. CONCLUSIONS: The survival of childhood cancer in Thailand has markedly improved. Since implementation of national protocols, this is particularly the case for ALL and NHL. These results may be generalizable for the whole country.

Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion-Dependent Thalassemia in Northeast Thailand.

Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular blood transfusion for survival but may encounter several complications that contribute to morbidity and mortality. We report the molecular heterogeneity and hematological features of NTDT in 312 adult patients in northeast Thailand. Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-ß-thalassemia, 1 with homozygous ß0-thalassemia and 134 with Hb H, AEBart's and EEBart's diseases. For ß-thalassemia, 12 different mutations including both ß0- and ß+-thalassemias were detected. Coinheritance of α-thalassemia as an ameliorating factor was observed in 18 of 178 cases (10.1%) with ß-thalassemia. The α-globin gene triplicated haplotype (αααanti3.7) was observed in 1 case of Hb E-ß0-thalassemia. The presence of the -158 (Cx2192;T) Gx03B3;-XmnI polymorphism (+/+) was found to be associated with increased Hb F expression, but its frequency in the studied subjects was low. Those with α-thalassemia included 17 with deletional and 51 nondeletional Hb H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological parameters of these NTDT and genotype-phenotype relationships are presented. The diverse molecular heterogeneity of NTDT underlines the importance of complete genotyping of the patient. These results should prove useful for management planning, the prediction of clinical outcome and to improve genetic counseling for NTDT patients.

Frataxin expression in reticulocytes of non-splenectomized and splenectomized patients with HbE-ß-thalassaemia.

OBJECTIVES: A previous report revealed that thalassaemic patients with transfusional iron overload developed oxidative stress. The aims of this study were to investigate the FXN mRNA levels in the reticulocytes of patients with HbE-beta-thalassaemia who were treated with regular transfusions, to compare the results with those from normal controls and to evaluate the relationships of the levels of FXN mRNA with malondialdehyde (MDA) and iron parameters in these patients. DESIGN AND METHODS: The levels of FXN mRNA in the reticulocytes of patients (30 non-splenectomized and 30 splenectomized) and 30 normal individuals were assessed by RT-PCR. The levels of MDA and the transferrin saturations (TSs) were analysed with thiobarbituric acid-reactive substance assay and spectrometry, respectively. The level of ferritin was determined by ELISA. RESULTS: The levels of FXN mRNA, MDA, ferritin, and TS in the patients were significantly higher than those in the controls. The levels of FXN mRNA, MDA, and ferritin in the non-splenectomized and splenectomized patients were significantly different, but the levels of TS in these two patient groups were comparable. The relative FXN expression in the patients was found to be correlated with the levels of MDA and ferritin but not correlated with TS. CONCLUSIONS: The elevation of FXN expression in the reticulocytes of these patients seems to be linked to oxidative stress and iron status.