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.

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.

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.

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.

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.

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.

Outcomes of thalassemia patients undergoing hematopoietic stem cell transplantation by using a standard myeloablative versus a novel reduced-toxicity conditioning regimen according to a new risk stratification.

Improving outcomes among class 3 thalassemia patients receiving allogeneic hematopoietic stem cell transplantations (HSCT) remains a challenge. Before HSCT, patients who were ≥ 7 years old and had a liver size ≥ 5 cm constitute what the Center for International Blood and Marrow Transplant Research defined as a very high-risk subset of a conventional high-risk class 3 group (here referred to as class 3 HR). We performed HSCT in 98 patients with related and unrelated donor stem cells. Seventy-six of the patients with age < 10 years received the more conventional myeloablative conditioning (MAC) regimen (cyclophosphamide, busulfan, ± fludarabine); the remaining 22 patients with age ≥ 10 years and hepatomegaly (class 3 HR), and in several instances additional comorbidity problems, underwent HSCT with a novel reduced-toxicity conditioning (RTC) regimen (fludarabine and busulfan). We then compared the outcomes between these 2 groups (MAC versus RTC). Event-free survival (86% versus 90%) and overall survival (95% versus 90%) were not significantly different between the respective groups; however, there was a higher incidence of serious treatment-related complications in the MAC group, and although we experienced 6 graft failures in the MAC group (8%), there were none in the RTC group. Based on these results, we suggest that (1) class 3 HR thalassemia patients can safely receive HSCT with our novel RTC regimen and achieve the same excellent outcome as low/standard-risk thalassemia patients who received the standard MAC regimen, and further, (2) that this novel RTC approach should be tested in the low/standard-risk patient population.

Effect of genotype on pulmonary hypertension risk in patients with thalassemia.

INTRODUCTION: Pulmonary hypertension is one of the major complications in patients with non-transfusion-dependent thalassemia (NTDT). Patients with NTDT have distinct genetic subgroups. Therefore, the effects of different genotype groups on pulmonary hypertension risk in patients with NTDT were assessed. METHODS: A cross-sectional study was conducted in patients with NTDT aged ≥ 10 yr old at Srinagarind University Hospital and Udonthani Hospital, Thailand. Pulmonary hypertension risk was defined as peak tricuspid regurgitation velocity > 2.9 m/s by trans-thoracic echocardiography. Clinical characteristics and laboratory data that literature has indicated as risk factors for pulmonary hypertension were collected. The effect of genotype group on pulmonary hypertension risk was evaluated by using multivariate logistic regression analysis. RESULTS: Of 219 patients, pulmonary hypertension risk was found in 24 patients (10.96%). All patients were categorized into two groups according to genetic data that included: (i) ß-thalassemia (139, 63.5%), (ii) α-thalassemia and combined α and ß-thalassemia (80, 36.5%). Genotype groups were statistically and significantly associated with pulmonary hypertension risk based on the adjusted odds ratios after adjustment for other factors. Patients with ß-thalassemia had a statistically significant higher risk for pulmonary hypertension risk (odds ratio = 9.47, P = 0.036) compared to patients with α-thalassemia and patients with combined α and ß-thalassemia. CONCLUSION: The genotype group is an independent risk factor for pulmonary hypertension in patients with NTDT. Echocardiography should be routinely recommended for all patients with ß-thalassemia. Routine screening in patients with α-thalassemia and combined α and ß-thalassemia, however, may not be necessary or should focus on the older population.

IMPAIRED ENDOTHELIAL FUNCTION IN PEDIATRIC HEMOGLOBIN E/ß-THALASSEMIA PATIENTS WITH IRON OVERLOAD.

Hemoglobin E/ß-thalassemia (HbE/ß-thalassemia) is the most important type of thalassemia in northeastern Thailand. Serious complications of the disease are associated with iron overload and the consequences of oxidative damage to various organs, especially the cardiovascular system. Endothelial dysfunction is an important predictor for the long-term outcome of the disease. In this study, 19 patients with HbE/ß-thalassemia (aged 12.9 ± 2.8 years) and 18 healthy controls (aged 11.8 ± 1.6 years) were enrolled and their oxidant and antioxidant status was determined. Their vascular endothelial function was assessed by ultrasonographic measurement of flow-mediated dilation (FMD) of the brachial artery. The thalassemia patients were found to have higher levels of oxidative stress (based on plasma levels of malondialdehyde and protein carbonyls) and significantly reduced antioxidant levels [based on levels of glutathione (GSH) in whole blood (p < 0.001)]. Thalassemia patients showed endothelial dysfunction as shown by their FMD response during reactive hyperemia (p < 0.001). The degree of impaired FMD response was correlated with the age, hemoglobin levels and serum free iron levels of subjects (p < 0.05). In conclusion, the FMD response was reduced in children with HbE/ß-thalassemia and the degree of this reduction was correlated with the severity of anemia. FMD can be used for clinical evaluation of endothelial dysfunction, which could be an independent predictor of the cardiovascular events of thalassemia patients.

Pretransplant immunosuppression followed by reduced-toxicity conditioning and stem cell transplantation in high-risk thalassemia: a safe approach to disease control.

Patients with class 3 thalassemia with high-risk features for adverse events after high-dose chemotherapy with hematopoietic stem cell transplantation (HSCT) are difficult to treat, tending to either suffer serious toxicity or fail to establish stable graft function. We performed HSCT in 18 such patients age ≥7 years and hepatomegaly using a novel approach with pretransplant immunosuppression followed by a myeloablative reduced-toxicity conditioning regimen (fludarabine and i.v. busulfan [Flu-IV Bu]) and then HSCT. The median patient age was 14 years (range, 10 to 18 years). Before the Flu-IV Bu + antithymocyte globulin conditioning regimen, all patients received 1 to 2 cycles of pretransplant immunosuppression with fludarabine and dexamethasone. Thirteen patients received a related donor graft, and 5 received an unrelated donor graft. An initial prompt engraftment of donor cells with full donor chimerism was observed in all 18 patients, but 2 patients developed secondary mixed chimerism that necessitated withdrawal of immunosuppression to achieve full donor chimerism. Two patients (11%) had acute grade III-IV graft-versus-host disease, and 5 patients had limited chronic graft-versus-host disease. The only treatment-related mortality was from infection, and with a median follow-up of 42 months (range, 4 to 75), the 5-year overall survival and thalassemia-free survival were 89%. We conclude that this novel sequential immunoablative pretransplantation conditioning program is safe and effective for patients with high-risk class 3 thalassemia exhibiting additional comorbidities.

Association of Hb Thailand [α56(E5)Lys→Thr] and Hb Phnom Penh [α117(GH5)-Ile-α118(H1)] with α(0)-thalassemia: molecular and hematological features and differential diagnosis.

We report the molecular and hematological characteristics of two rare hemoglobin (Hb) variants found in associations with a common α(0)-thalassemia (α(0)-thal) in Thai patients. The first case (P1) was a generally healthy 27-year-old man discovered during our ongoing thalassemia screening program. Hemoglobin and DNA analyses identified a previously undescribed condition of compound heterozygosity for Hb Thailand [α56(E5)Lys→Thr] and α(0)-thal (SEA deletion). The second case (P2) was a 4-year-old boy with hypochromic microcytic anemia. Hemoglobin and DNA analyses also identified a compound heterozygosity for Hb Phnom Penh [α117(GH5)-Ile-α118(H1)] in association with α(0)-thal (SEA deletion). Although Hb H (ß(4)) inclusion bodies were observed in both cases, Hb analysis using both high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) did not show Hb H. While the two Hb variants could be recognized on Hb HPLC analysis, their corresponding Hb A(2) derivatives: the Hb A(2)-Thailand and Hb A(2)-Phnom Penh, were clearly observed on CE. Apparently, combination of these two Hb variants with α(0)-thal are not expressed as Hb H disease. The two Hb variants could be confirmed by polymerase chain restriction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR assays.

Comparison of hematocrit/hemoglobin ratios in subjects with alpha-thalassemia, with subjects having chronic kidney disease and normal subjects.

The ratio of hematocrit (Hct) to hemoglobin (Hb) in the people with normal red blood cell (RBC) morphology is generally three to one. We studied Hct/Hb ratios among patients with alpha-thalassemias (Hb H, H-CS, AEBart, AEBart-CS, EFBart and EFBart-CS diseases) diagnosed by high performance liquid chromatography, and compared them with normal subjects and with patients having anemia due to chronic kidney disease (CKD). The Hct and Hb levels were derived by automated analyzer. The means +/- SD of the Hct/Hb ratios were 3.5 +/- 0.2 (range 3.3 - 4.1), 3.0 +/- 0.1 (range 2.9 - 3.2) and 3.0 +/- 0.1 (range 2.8 - 3.2) in the alpha-thalassemia, normal and CKD groups, respectively. The mean Hct/Hb ratio in subjects with alpha-thalassemia was higher than the mean in normal subjects and in those with CKD. The Hct/Hb ratios for each genotype of the alpha-thalassemia were not different from each other. The underlying mechanisms for the higher Hct/Hb ratio among those with alpha-thalassemia are theorized to be less density and/or more hydration of a-thalassemia RBCs, more entrapment of plasma in the spun RBC, the high percent of nucleated RBC and WBC interference. A ratio of 3.5 +/- 0.2 may be helpful in cases of moderate anemia when typing only shows Hb A and E, to consider investigation for alpha-thalassemia, or in cases of alpha-thalassemia with acute blood loss, if the Hct is less than 35%, in the decision to transfuse.

Altered vascular function, arterial stiffness, and antioxidant gene responses in pediatric thalassemia patients.

Patients with thalassemia major are susceptible to cardiovascular complications by mechanisms not fully understood. Although overt cardiovascular complications usually occur after puberty, their underlying pathogenesis may begin much earlier. This study investigated whether there were early changes in vascular endothelial function and arterial stiffness in young patients with beta-thalassemia and hemoglobin E, and whether these changes were associated with oxidative stress and expression of antioxidant genes. The study recruited 30 pediatric patients and 30 age-matched control subjects. Compared with the control subjects, the patients had increased levels of oxidant biomarkers including malondialdehyde, protein carbonyl, and non-transferrin-bound iron and a decreased glutathione redox ratio. There were clear signs of vascular endothelial dysfunction and increased arterial stiffness, as shown by marked suppression of forearm blood flow after reactive hyperemia and increased pulse-wave velocity in the trunk and legs. The changes in FBF were associated with oxidative stress markers and free iron. An adaptive antioxidant gene response was activated in blood mononuclear cells, as shown by upregulation of GCLC and Bach-1 mRNA but downregulation of heme oxygenase-1 and thioredoxin mRNA. The results highlight the vascular changes seen even in young patients during treatment. These changes were associated with oxidative stress and suggest an adaptive response that serves to protect host cells from further oxidative damage.

Childhood neoplasms: analysis of Thai children 2010.

BACKGROUND: Between 1990 and 2010, many national and international factors converged to both beneficially and antagonistically affect people's health as well as the Thai healthcare system. Among these were: a falling birth rate in Thailand and a gradual decline in poverty-related diseases. Cancer becomes the most common cause of death. OBJECTIVE: To analyze Thailand's childhood neoplasm issues for baseline information for changing medical education, services and research. MATERIAL AND METHOD: Information on the illnesses of in-patients, out-patients and casualties was based on hospital withdrawals nationwide from the three health insurance schemes in the fiscal year 2010. The data, which included 96% of the population, were analyzed by age groups and burden of neoplasm disease. RESULTS: The children with neoplasms were treated 127,597 times at outpatient departments (OPD) and 19,159 times at inpatient departments (IPD) at community hospitals (4.3%), provincial hospitals (8.50%), regional or university hospitals (86.1%) and private hospitals (1.1%). Malignant neoplasms of lymphoid hematopoietic and related tissues were the most common in both IPD and OPD settings, which resulted in the highest cost of treatment. Tumors of the central nervous system were associated with the highest cost. The mean length of stay for all patients with neoplasm was 7.85 days. CONCLUSION: Sufficient budget should be allocated to the more heavily frequented treatment center Specific and better care, national treatment protocols for each type of childhood cancer (including palliative care) should be developed to improve the treatment outcomes and/or the quality of life. Medical schools and health service systems need to be recalibrated to respond proactively to these changes being experienced by the healthcare system.

Health situation analysis of Thai children aged 1-5 years in 2010: implications for health education and health service reform.

BACKGROUND: To make the world fit for children is a task necessarily involves all organizations working with children. The real health situation will be useful for strategic planning for them. OBJECTIVE: To emphasize Thailand's health burdens of children between 1 and 5 years in 2010. MATERIAL AND METHOD: The authors analyzed the fiscal 2010 data from the three health insurance schemes from hospitals nationwide for information on: out-patient and in-patient visits, common illnesses of Thai children between 1 and 5 years, lengths of stay, hospital charges and deaths. Most (96%) of the population was represented in this data. RESULTS: Respiratory infection was the most common admission (225,183 times) while intestinal infection was the second (83,293 times). Respiratory infection was the second most common for an out-patient visit (7, 387,132 times = 23.6%) after other factors influencing health (17,384,963 times = 55.5%). The most common causes of death were injury and poisoning (178 patients) and respiratory infection (175 patients). Pneumonia required the most budget and resulted in the longest stays. Among accidents, accidental drowning and submersion caused the most deaths. CONCLUSION: Respiratory infection, pneumonia, intestinal infection, injuries, poisoning and accidental drowning were the most common health burdens among children between 1 and 5 years of age.

Unintentional injury among Thai children and adolescents in 2010.

BACKGROUND: Unintentional injury has been identified as a public health problem in Thailand as it is the leading cause of death among both children and adolescents. OBJECTIVE: To explore the number of admissions by unintentional injury and cause(s) among Thai children and adolescents in 2010. MATERIAL AND METHOD: Data on the number of admissions by unintentional injury in the fiscal year, 2010, were derived from hospitals nationwide as well as the three health insurance schemes. Data on Thai children and adolescents (0-18 years) was collected between October 1, 2009 and September 30, 2010. The coding for underlying cause(s) of unintentional injuries and death were done using the International Classification of Diseases, 10th edition. RESULTS: A total of 118,323 unintentional injuries were reported. The majority of patients were male and falls were the major cause of unintentional injuries (27,139 admissions; 22.94%) followed by motorcycle injuries (20,499 admissions; 17.32%). Accidental drowning and submersion was the major cause of death in the present study, followed by lightning strikes and accidental threats to breathing (i.e., choking and suffocation). CONCLUSION: The current study revealed that falls were the major cause of unintentional injury and accidental drowning and submersion the major cause of death.

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.

Hemoglobin Lepore EF Bart's disease: a molecular, hematological, and diagnostic aspects.

We report the molecular basis and hematological phenotype associated with a hitherto undescribed interaction of hemoglobin (Hb) Lepore-Hollandia, Hb E and a deletion of three α-globin genes found in a 3-year-old Thai girl. She had mild anemia with Hb 10.9 g/dl and Hct 35.9% and had never received blood transfusion. Hb analysis revealed Hb E (22.1%) with a normal level of Hb A(2) (1.9%), unusually elevated Hb F (65.9%), Hb Lepore (4.0%), and 5.4% Hb Bart's. Globin gene analyses demonstrated that she carried the Hb Lepore-Hollandia mutation in trans to the Hb E and a compound heterozygosity for α(0)-thalassemia (SEA deletion) and α(+)-thalassemia (3.7 kb deletion), leading to the Hb Lepore EF Bart's disease. Hematological data and diagnostics using combined Hb-HPLC, capillary electrophoresis, and PCR analysis of this condition were presented and compared with those of the patients with other forms of EF Bart's disease and EE Bart's disease in our series.