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Papers by PACHARAPAN Surapolchai

Research paper thumbnail of Phenotypic and genotypic analysis of patients with congenital factor VII deficiency in a multicenter study in Thailand

Pediatric Hematology Oncology Journal

Research paper thumbnail of Red blood cell alloimmunization and other transfusion‐related complications in patients with transfusion‐dependent thalassemia: A multi‐center study in Thailand

Research paper thumbnail of Pediatric primary central nervous system tumors registry in Thailand under National Health Security Office schemes

Journal of Neuro-Oncology, 2020

Background Few epidemiological studies of pediatric central nervous system (CNS) tumors have been... more Background Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. Methods Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003-2005 (before establishment of a pediatric CNS tumor protocol) and 2011-2012 (post-establishment). Results The first study period had 300 patients with an incidence of 7.5/1,000,000 person-years and the second had 168 patients with an incidence of 13.24/1,000,000 person-years. The three most common tumors were gliomas, medulloblastoma/ primitive neuroectodermal tumor (PNET), and germ cell tumors. The most common tumor site was the cerebellum, followed by the brainstem and pineal region. Five-and 10-year overall survival (OS) rates were 46.62% (95% confidence interval [CI] 40.85-52.18) and 41.78% (95% CI 36.11-47.34), respectively, for the first period. The second period had a 5-year OS of 64.75% (95% CI 56.70-71.68). OS rates for gliomas, germ cell tumors, medulloblastoma/PNET, and ependymomas were better in the second period than in the first period. Conclusions The incidence of primary childhood CNS tumors in our study is lower compared with other reports. Improvement of OS in the second study period might be because of establishment of the Thai Pediatric Oncology Group, and national protocols for childhood CNS tumors.

Research paper thumbnail of Genetic Polymorphisms of β-Cell Differentiation Confer Risk of Alterations of Glucose Metabolism in Survivors of Childhood Acute Lymphoblastic Leukemia

Blood, 2008

Purpose: Long-term survivors of acute lymphoblastic leukemia (ALL) seem to be at risk of insulin ... more Purpose: Long-term survivors of acute lymphoblastic leukemia (ALL) seem to be at risk of insulin resistance, impaired glucose tolerance and may develop typical signs of metabolic syndrome with disturbances in lipid metabolism. The aim of the present study was to study the prevalence of alterations in glucose metabolism and the predisposing factors of these disturbances in survivors of childhood ALL. Furthermore, we intended to identify the role of such genetic polymorphisms affecting β-cell function and glucose metabolism and possibly to develop them as markers for monitoring β-cell dysfunction following treatment for ALL in the future. Patients and methods: In 131 ALL survivors after cessation of therapy, an oral glucose tolerance test was performed to determine β-cell function/insulin sensitivity. Six single-nucleotide polymorphisms of PAX4 and TCF7L2 genes were genotyped in order to evaluate the association between these polymorphisms and β-cell function/insulin sensitivity. Resu...

Research paper thumbnail of Outcomes of Children with Acute Lymphoblastic Leukemia Treated with 2 Consecutive Protocols: Ramathibodi Hospital Experience

Blood, 2008

We determined the outcomes and prognostic factors of children (age, 0.8 to 14.8 years) with acute... more We determined the outcomes and prognostic factors of children (age, 0.8 to 14.8 years) with acute lymphoblastic leukemia (ALL) treated with 2 consecutive protocols between 1997 and 2008. The risk classification was followed NCI criteria. One hundred and one patients, (60 males and 41 females), were enrolled to the first protocol (modified St Jude Total XIII) (1997–2003). Ninety seven patients (96%) of these 101 patients achieved remission after induction. The event free survival (EFS) rates were 90.1 ± 3%, 85 ± 3.6%, and 83.8 ± 3.7%, and the cumulative risk of CNS relapse were 2.1 ± 1.5%, 3.2 ± 1.8%, and 3.2 ± 1.8%, at 3, 5, and 10 years, respectively. The median follow-up time for patients remaining free of adverse events was 6.8 years (4.2–10.3 years). The adverse prognostic factors included obesity (p =0.013), high risk group (p= 0.012), minimal residual leukemia (MRD) presence (> 0.01%) on day 15 of induction (p <0.001) and sepsis during treatment (p= 0.003). For the secon...

Research paper thumbnail of Long-Term Outcomes of Modified St Jude Children’s Research Hospital Total Therapy XIIIB and XV Protocols for Thai Children With Acute Lymphoblastic Leukemia

Clinical Lymphoma Myeloma and Leukemia, 2019

BACKGROUND We studied long-term outcomes and prognostic features of Thai children with acute lymp... more BACKGROUND We studied long-term outcomes and prognostic features of Thai children with acute lymphoblastic leukemia treated with modified St Jude Children's Research Hospital (SJCRH) protocols. PATIENTS AND METHODS Pediatric patients newly diagnosed with acute lymphoblastic leukemia were included. From 1997 to 2003, the first group received modified Total Therapy XIIIB (previous protocol). From 2004 to 2014, the latter had modified Total Therapy XV (current protocol). RESULTS In 250 patients, the event-free survival rates (± standard error) of the previous protocol (n = 95) were 82.8 ± 3.9%, 81.7 ± 4.0%, and 81.7 ± 4.0% at 5, 10, and 15 years, respectively; current protocol event-free survival rates (n = 155) were 84 ± 3.0%, 80.8 ± 3.4%, and 80.8 ± 3.4%, respectively. Previous protocol overall survival rates for the same years were 89.2 ± 3.2%, 84.8 ± 3.8%, and 84.8 ± 3.8%, and for the current protocol were 90 ± 2.5%, 86.9 ± 3.2%, and 83.7 ± 4.4%. Previous protocol relapses were 10.5% (10 patients), with 7 having isolated hematologic and 3 isolated/combined central nervous system relapses. Current protocol relapses were 9.7% (15 patients), with 7 having isolated hematologic, 6 isolated/combined central nervous system, and 2 extramedullary relapses. Patients with leukocyte counts over 100 × 109/L and who had disease classified as high risk had worse event-free survival using the previous protocol. However, only initial leukocyte counts of ≥ 100 × 109/L predicted adverse outcomes under the current protocol. Minimal residual disease positivity was a prognostic factor of worse overall survival only for previous protocol patients. CONCLUSION Favorable outcomes of childhood acute lymphoblastic leukemia occurred using adapted SJCRH protocols, perhaps because of multidisciplinary care teams and improved parent advocacy. Inferior outcomes might be prevented by addressing predictive factors to ameliorate monitoring and care.

Research paper thumbnail of Predictors of severe adverse outcomes in febrile neutropenia of pediatric oncology patients at a single institute in Thailand

Pediatric Hematology and Oncology, 2020

Febrile neutropenia in pediatric oncology patients may lead to severe infection, with adverse eve... more Febrile neutropenia in pediatric oncology patients may lead to severe infection, with adverse events including septic shock or death. The aim of the study was to investigate the prevalence of severe adverse outcomes and to determine the associated risk factors. This is a retrospective cohort study of pediatric oncology patients with febrile neutropenia from

Research paper thumbnail of In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency

Nature Biotechnology, 2015

Research paper thumbnail of A molecular study on the role of alpha-hemoglobin-stabilizing protein in hemoglobin H disease

Annals of hematology, Jan 23, 2017

The clinical course of hemoglobin H (HbH) disease is remarkably variable. It is not completely cl... more The clinical course of hemoglobin H (HbH) disease is remarkably variable. It is not completely clear how genetic and environmental factors interplay to modify clinical severity in affected individuals. Previous studies suggested that altered structure or function of alpha-hemoglobin-stabilizing protein (AHSP) could modify the clinical phenotypes of thalassemias. The present study attempted to explore the potential role of AHSP in the pathophysiology of HbH disease in 95 Chinese and Thai/Sino-Thai patients with deletional and non-deletional form of this disease. We identified six polymorphic sites in AHSP which were subgrouped into major haplotype clades. No association between AHSP genotypes or haplotypes and clinical phenotypes was observed. Instead, multiple linear regression analysis indicated that expression of AHSP correlated negatively with age (P < 0.001) and hemoglobin (P = 0.007), but positively with reticulocyte count (P = 0.003) and severity score (P = 0.003). Subgroup...

Research paper thumbnail of Biopsychosocial predictors of health-related quality of life in children with thalassemia in Thammasat University Hospital

Journal of the Medical Association of Thailand Chotmaihet Thangphaet, Dec 1, 2010

To determine health-related quality of life (HRQOL) in children with thalassemia in order to expl... more To determine health-related quality of life (HRQOL) in children with thalassemia in order to explore physical and psychosocial factors affecting on their QOL. A cross-sectional study was conducted at Thammasat University Hospital, Pathum Thani. Sociodemographic factors and clinical characteristics were obtained from seventy-five of transfusion-dependent and non-transfused thalassemia patients. The PedsQL 4.0 Generic Core Scales (Thai version) were administered to determine the patients and their parents&amp;amp;amp;amp;amp;amp;#39; perspectives. The mean (SD) of total HRQOL score was 78.50 (2.05) for children who were self-reporting and it was 73.41 (2.22) for parent proxy-report, that were comparable with population norms. The stepwise multiple regression analysis indicated that total HRQOL score of child self-report was negatively predicted by lower family income, early age onset of anemia before 2 years and under covered by Universal Health Coverage Scheme. The negative predictors of total HRQOL score of parent proxy-report were regular transfusion every 1-2 months, while self medical payment was positively predictive. The HRQOL in children with thalassemia was not only determined by disease severity and treatment but also by family financial impacts for caring of children. Health care interventions should be implemented to support in various domains of life.

Research paper thumbnail of Modified desensitization protocols for a pediatric patient with anaphylactic reaction to deferoxamine

Journal of the Medical Association of Thailand Chotmaihet Thangphaet, Aug 1, 2014

Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload ... more Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload due to regular blood transfusions. Deferoxamine is used as chelating agentfor treatment ofpatients with chronic iron overload worldwide. Anaphylactic reaction to deferoxamine is rare, and the mechanism ofdeferoxamine-induced anaphylaxis is not well understood. Only afewpediatric cases ofsuccessful desensitization for deferoxamine hypersensitivity have been described, and a different protocol has been used in each report. We report a case ofanaphylaxis to deferoxamine in a thirteen-years-old Thai boy with Hemoglobin E/β-thalassemia disease who underwent successful desensitization. He had been receiving blood transfusions since the age often months. At age eleven, the patient began treatment with deferoxamine. Treatment was interrupted after the occurrence ofanaphylaxis, with urticaria, wheezing and gastrointestinal symptoms. A skin prick test was positive, indicating a type 1 hypersensitivity reaction. Deferoxamine desensitization was attempted with various differentprotocols. Finally, the patient could tolerate deferoxamine therapy at the dose previously administered. We proposed this modified subcutaneous desensitization protocolforpediatric cases that develop allergic reactions to deferoxamine.

Research paper thumbnail of Curative Stem Cell Transplantation for Severe Hb H Disease Manifesting From Early Infancy: Phenotypic and Genotypic Analyses

Hemoglobin, 2015

Most people with Hb H disease live normal lives; however, a minority of cases requires lifelong r... more Most people with Hb H disease live normal lives; however, a minority of cases requires lifelong regular transfusions. An atypical form of nondeletional Hb H disease was reported in a Thai boy, characterized by severe persistent hemolytic anemia since the age of 2 months. Molecular diagnosis revealed the apparent compound heterozygosity for the Southeast Asian (- -(SEA)) and α2 polyadenylation (polyA) signal (AATAAA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;AATA- -) deletions. The proband was successfully treated with allogeneic hematopoietic stem cell transplantation (HSCT). Accurate phenotypic and genotypic diagnosis in atypically severe Hb H disease is helpful for the understanding of its pathophysiology, the institution of appropriate management, and provision of genetic counseling and prenatal diagnosis. Hematopoietic stem cell transplantation is a potentially curative treatment option for this severe α-thalassemia (α-thal) syndrome.

Research paper thumbnail of Hemophagocytic lymphohistiocytosis

Research paper thumbnail of Modified desensitization protocols for a pediatric patient with anaphylactic reaction to deferoxamine

Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2014

Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload ... more Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload due to regular blood transfusions. Deferoxamine is used as chelating agentfor treatment ofpatients with chronic iron overload worldwide. Anaphylactic reaction to deferoxamine is rare, and the mechanism ofdeferoxamine-induced anaphylaxis is not well understood. Only afewpediatric cases ofsuccessful desensitization for deferoxamine hypersensitivity have been described, and a different protocol has been used in each report. We report a case ofanaphylaxis to deferoxamine in a thirteen-years-old Thai boy with Hemoglobin E/β-thalassemia disease who underwent successful desensitization. He had been receiving blood transfusions since the age often months. At age eleven, the patient began treatment with deferoxamine. Treatment was interrupted after the occurrence ofanaphylaxis, with urticaria, wheezing and gastrointestinal symptoms. A skin prick test was positive, indicating a type 1 hypersensiti...

Research paper thumbnail of Biopsychosocial predictors of health-related quality of life in children with thalassemia in Thammasat University Hospital

Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2010

To determine health-related quality of life (HRQOL) in children with thalassemia in order to expl... more To determine health-related quality of life (HRQOL) in children with thalassemia in order to explore physical and psychosocial factors affecting on their QOL. A cross-sectional study was conducted at Thammasat University Hospital, Pathum Thani. Sociodemographic factors and clinical characteristics were obtained from seventy-five of transfusion-dependent and non-transfused thalassemia patients. The PedsQL 4.0 Generic Core Scales (Thai version) were administered to determine the patients and their parents' perspectives. The mean (SD) of total HRQOL score was 78.50 (2.05) for children who were self-reporting and it was 73.41 (2.22) for parent proxy-report, that were comparable with population norms. The stepwise multiple regression analysis indicated that total HRQOL score of child self-report was negatively predicted by lower family income, early age onset of anemia before 2 years and under covered by Universal Health Coverage Scheme. The negative predictors of total HRQOL score o...

Research paper thumbnail of Challenges in the diagnosis and treatment of juvenile myelomonocytic leukaemia in Hong Kong over the past two decades

Hong Kong Journal of Paediatrics

Research paper thumbnail of Comparative outcomes of Thai children with acute lymphoblastic leukemia treated with two consecutive protocols: 11-year experience

Leukemia & Lymphoma, 2012

The aim of this study was to determine outcomes and prognostic features of children with acute ly... more The aim of this study was to determine outcomes and prognostic features of children with acute lymphoblastic leukemia (ALL) treated with two modified St Jude Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Research Hospital protocols at Ramathibodi Hospital (1997-2008). Event-free survival rates of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;previous protocol&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were 88.3 ± 3.3% and 83.0 ± 3.9% and of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;current protocol&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were 89.9 ± 3.4% and 88.0 ± 3.8%, at 3 and 5 years, respectively. Adverse prognostic features were identified only in the previous protocol study, including obesity, presenting leukocytes &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;100 × 10(9)/L, high-risk group, persistent blasts in a day-15 marrow and sepsis. Sepsis also conferred inferior overall survival rates of patients in both protocols. Steady improvement in cure rate over the past decade has clearly demonstrated the optimal use of treatment protocols and a multidisciplinary approach to implementing pediatric cancer care in Ramathibodi Hospital. Our future challenges are refinement in risk and treatment stratification and reduction of treatment-related toxicities, prioritizing death from infections.

Research paper thumbnail of Central Diabetes Insipidus

Journal of Pediatric Hematology/Oncology, 2013

Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syn... more Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

Research paper thumbnail of Impaired Glucose Tolerance and Insulin Resistance in Heart Failure: Underrecognized and Undertreated?

Journal of Cardiac Failure, 2010

A link between diabetes mellitus (DM) and heart failure (HF) has been well-recognized for more th... more A link between diabetes mellitus (DM) and heart failure (HF) has been well-recognized for more than a century. HF is also closely linked to abnormal glucose regulation (AGR) and insulin resistance (IR) in patients without DM and, similarly, these conditions commonly coexist. In epidemiological studies, each condition appears to predict the other. The prevalence of AGR/IR in HF patients without DM is significantly underrecognized and, as yet, the optimal method for screening for these abnormalities in the outpatient setting is unclear. The purpose of this review is to overview the prevalence and prognostic impact of AGR and IR in HF patients without DM and discuss potential pathophysiological pathways that link these conditions with HF. The severity of glucose intolerance in patients with HF correlates with functional and clinical severity of HF and is an independent predictor of an adverse outcome. It is thought that changes in cardiac metabolism, including a switch from glucose metabolism toward fatty acid metabolism, may in part contribute to the pathophysiological processes associated with HF patients with AGR/IR. We discuss how pharmacological targeting of metabolic pathways in the myocardium of these patients with HF may represent novel therapeutic strategies in these at-risk patients.

Research paper thumbnail of Widening Spectrum of Liver Angiosarcoma in Children

Objectives: Liver hemangiomas are vascular tumors, which occur in the first months of life and ca... more Objectives: Liver hemangiomas are vascular tumors, which occur in the first months of life and carry risks of initial complications, but are considered to be benign histologically and to regress with time. Histologic studies suggest that a subtype, type 2 hemangioendothelioma, is akin to angiosarcoma and may have a severe long-term prognosis. We report 5 girls with type 2 hemangioendothelioma of the liver. Methods and Results: Three children initially presented with classical infantile multinodular hemangioma, including cardiac and pulmonary complications and regression of tumors at age 1 1 /2 to 2 1 /2 years. All 3 experienced tumor relapse at ages 2 1 /2 to 3, leading to death at ages 2 1 /2 to 5. Tumor histology showed type 2 hemangioendothelioma. The other 2 children presented with liver tumors at ages 2 and 3 years. In 1, initial biopsy of a single tumor showed benign type 1 hemangioendothelioma, but surgical resection was followed by relapse in the remaining liver, lung metastases, and death. Whole tumor histology showed both type 1 and 2 lesions. In the other child, tumor biopsy showed type 2 lesions. She underwent liver transplantation and is alive without tumor recurrence 3 years later. Conclusions: Careful follow-up is necessary to detect late recurrence in infants with multinodular liver hemangiomas. Vascular liver tumors occurring after infancy are likely to be malignant. The high risk of relapse in the remaining liver suggests that if no metastases are detected, liver transplantation is preferable to surgical tumor resection in both situations.

Research paper thumbnail of Phenotypic and genotypic analysis of patients with congenital factor VII deficiency in a multicenter study in Thailand

Pediatric Hematology Oncology Journal

Research paper thumbnail of Red blood cell alloimmunization and other transfusion‐related complications in patients with transfusion‐dependent thalassemia: A multi‐center study in Thailand

Research paper thumbnail of Pediatric primary central nervous system tumors registry in Thailand under National Health Security Office schemes

Journal of Neuro-Oncology, 2020

Background Few epidemiological studies of pediatric central nervous system (CNS) tumors have been... more Background Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. Methods Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003-2005 (before establishment of a pediatric CNS tumor protocol) and 2011-2012 (post-establishment). Results The first study period had 300 patients with an incidence of 7.5/1,000,000 person-years and the second had 168 patients with an incidence of 13.24/1,000,000 person-years. The three most common tumors were gliomas, medulloblastoma/ primitive neuroectodermal tumor (PNET), and germ cell tumors. The most common tumor site was the cerebellum, followed by the brainstem and pineal region. Five-and 10-year overall survival (OS) rates were 46.62% (95% confidence interval [CI] 40.85-52.18) and 41.78% (95% CI 36.11-47.34), respectively, for the first period. The second period had a 5-year OS of 64.75% (95% CI 56.70-71.68). OS rates for gliomas, germ cell tumors, medulloblastoma/PNET, and ependymomas were better in the second period than in the first period. Conclusions The incidence of primary childhood CNS tumors in our study is lower compared with other reports. Improvement of OS in the second study period might be because of establishment of the Thai Pediatric Oncology Group, and national protocols for childhood CNS tumors.

Research paper thumbnail of Genetic Polymorphisms of β-Cell Differentiation Confer Risk of Alterations of Glucose Metabolism in Survivors of Childhood Acute Lymphoblastic Leukemia

Blood, 2008

Purpose: Long-term survivors of acute lymphoblastic leukemia (ALL) seem to be at risk of insulin ... more Purpose: Long-term survivors of acute lymphoblastic leukemia (ALL) seem to be at risk of insulin resistance, impaired glucose tolerance and may develop typical signs of metabolic syndrome with disturbances in lipid metabolism. The aim of the present study was to study the prevalence of alterations in glucose metabolism and the predisposing factors of these disturbances in survivors of childhood ALL. Furthermore, we intended to identify the role of such genetic polymorphisms affecting β-cell function and glucose metabolism and possibly to develop them as markers for monitoring β-cell dysfunction following treatment for ALL in the future. Patients and methods: In 131 ALL survivors after cessation of therapy, an oral glucose tolerance test was performed to determine β-cell function/insulin sensitivity. Six single-nucleotide polymorphisms of PAX4 and TCF7L2 genes were genotyped in order to evaluate the association between these polymorphisms and β-cell function/insulin sensitivity. Resu...

Research paper thumbnail of Outcomes of Children with Acute Lymphoblastic Leukemia Treated with 2 Consecutive Protocols: Ramathibodi Hospital Experience

Blood, 2008

We determined the outcomes and prognostic factors of children (age, 0.8 to 14.8 years) with acute... more We determined the outcomes and prognostic factors of children (age, 0.8 to 14.8 years) with acute lymphoblastic leukemia (ALL) treated with 2 consecutive protocols between 1997 and 2008. The risk classification was followed NCI criteria. One hundred and one patients, (60 males and 41 females), were enrolled to the first protocol (modified St Jude Total XIII) (1997–2003). Ninety seven patients (96%) of these 101 patients achieved remission after induction. The event free survival (EFS) rates were 90.1 ± 3%, 85 ± 3.6%, and 83.8 ± 3.7%, and the cumulative risk of CNS relapse were 2.1 ± 1.5%, 3.2 ± 1.8%, and 3.2 ± 1.8%, at 3, 5, and 10 years, respectively. The median follow-up time for patients remaining free of adverse events was 6.8 years (4.2–10.3 years). The adverse prognostic factors included obesity (p =0.013), high risk group (p= 0.012), minimal residual leukemia (MRD) presence (> 0.01%) on day 15 of induction (p <0.001) and sepsis during treatment (p= 0.003). For the secon...

Research paper thumbnail of Long-Term Outcomes of Modified St Jude Children’s Research Hospital Total Therapy XIIIB and XV Protocols for Thai Children With Acute Lymphoblastic Leukemia

Clinical Lymphoma Myeloma and Leukemia, 2019

BACKGROUND We studied long-term outcomes and prognostic features of Thai children with acute lymp... more BACKGROUND We studied long-term outcomes and prognostic features of Thai children with acute lymphoblastic leukemia treated with modified St Jude Children's Research Hospital (SJCRH) protocols. PATIENTS AND METHODS Pediatric patients newly diagnosed with acute lymphoblastic leukemia were included. From 1997 to 2003, the first group received modified Total Therapy XIIIB (previous protocol). From 2004 to 2014, the latter had modified Total Therapy XV (current protocol). RESULTS In 250 patients, the event-free survival rates (± standard error) of the previous protocol (n = 95) were 82.8 ± 3.9%, 81.7 ± 4.0%, and 81.7 ± 4.0% at 5, 10, and 15 years, respectively; current protocol event-free survival rates (n = 155) were 84 ± 3.0%, 80.8 ± 3.4%, and 80.8 ± 3.4%, respectively. Previous protocol overall survival rates for the same years were 89.2 ± 3.2%, 84.8 ± 3.8%, and 84.8 ± 3.8%, and for the current protocol were 90 ± 2.5%, 86.9 ± 3.2%, and 83.7 ± 4.4%. Previous protocol relapses were 10.5% (10 patients), with 7 having isolated hematologic and 3 isolated/combined central nervous system relapses. Current protocol relapses were 9.7% (15 patients), with 7 having isolated hematologic, 6 isolated/combined central nervous system, and 2 extramedullary relapses. Patients with leukocyte counts over 100 × 109/L and who had disease classified as high risk had worse event-free survival using the previous protocol. However, only initial leukocyte counts of ≥ 100 × 109/L predicted adverse outcomes under the current protocol. Minimal residual disease positivity was a prognostic factor of worse overall survival only for previous protocol patients. CONCLUSION Favorable outcomes of childhood acute lymphoblastic leukemia occurred using adapted SJCRH protocols, perhaps because of multidisciplinary care teams and improved parent advocacy. Inferior outcomes might be prevented by addressing predictive factors to ameliorate monitoring and care.

Research paper thumbnail of Predictors of severe adverse outcomes in febrile neutropenia of pediatric oncology patients at a single institute in Thailand

Pediatric Hematology and Oncology, 2020

Febrile neutropenia in pediatric oncology patients may lead to severe infection, with adverse eve... more Febrile neutropenia in pediatric oncology patients may lead to severe infection, with adverse events including septic shock or death. The aim of the study was to investigate the prevalence of severe adverse outcomes and to determine the associated risk factors. This is a retrospective cohort study of pediatric oncology patients with febrile neutropenia from

Research paper thumbnail of In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency

Nature Biotechnology, 2015

Research paper thumbnail of A molecular study on the role of alpha-hemoglobin-stabilizing protein in hemoglobin H disease

Annals of hematology, Jan 23, 2017

The clinical course of hemoglobin H (HbH) disease is remarkably variable. It is not completely cl... more The clinical course of hemoglobin H (HbH) disease is remarkably variable. It is not completely clear how genetic and environmental factors interplay to modify clinical severity in affected individuals. Previous studies suggested that altered structure or function of alpha-hemoglobin-stabilizing protein (AHSP) could modify the clinical phenotypes of thalassemias. The present study attempted to explore the potential role of AHSP in the pathophysiology of HbH disease in 95 Chinese and Thai/Sino-Thai patients with deletional and non-deletional form of this disease. We identified six polymorphic sites in AHSP which were subgrouped into major haplotype clades. No association between AHSP genotypes or haplotypes and clinical phenotypes was observed. Instead, multiple linear regression analysis indicated that expression of AHSP correlated negatively with age (P < 0.001) and hemoglobin (P = 0.007), but positively with reticulocyte count (P = 0.003) and severity score (P = 0.003). Subgroup...

Research paper thumbnail of Biopsychosocial predictors of health-related quality of life in children with thalassemia in Thammasat University Hospital

Journal of the Medical Association of Thailand Chotmaihet Thangphaet, Dec 1, 2010

To determine health-related quality of life (HRQOL) in children with thalassemia in order to expl... more To determine health-related quality of life (HRQOL) in children with thalassemia in order to explore physical and psychosocial factors affecting on their QOL. A cross-sectional study was conducted at Thammasat University Hospital, Pathum Thani. Sociodemographic factors and clinical characteristics were obtained from seventy-five of transfusion-dependent and non-transfused thalassemia patients. The PedsQL 4.0 Generic Core Scales (Thai version) were administered to determine the patients and their parents&amp;amp;amp;amp;amp;amp;#39; perspectives. The mean (SD) of total HRQOL score was 78.50 (2.05) for children who were self-reporting and it was 73.41 (2.22) for parent proxy-report, that were comparable with population norms. The stepwise multiple regression analysis indicated that total HRQOL score of child self-report was negatively predicted by lower family income, early age onset of anemia before 2 years and under covered by Universal Health Coverage Scheme. The negative predictors of total HRQOL score of parent proxy-report were regular transfusion every 1-2 months, while self medical payment was positively predictive. The HRQOL in children with thalassemia was not only determined by disease severity and treatment but also by family financial impacts for caring of children. Health care interventions should be implemented to support in various domains of life.

Research paper thumbnail of Modified desensitization protocols for a pediatric patient with anaphylactic reaction to deferoxamine

Journal of the Medical Association of Thailand Chotmaihet Thangphaet, Aug 1, 2014

Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload ... more Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload due to regular blood transfusions. Deferoxamine is used as chelating agentfor treatment ofpatients with chronic iron overload worldwide. Anaphylactic reaction to deferoxamine is rare, and the mechanism ofdeferoxamine-induced anaphylaxis is not well understood. Only afewpediatric cases ofsuccessful desensitization for deferoxamine hypersensitivity have been described, and a different protocol has been used in each report. We report a case ofanaphylaxis to deferoxamine in a thirteen-years-old Thai boy with Hemoglobin E/β-thalassemia disease who underwent successful desensitization. He had been receiving blood transfusions since the age often months. At age eleven, the patient began treatment with deferoxamine. Treatment was interrupted after the occurrence ofanaphylaxis, with urticaria, wheezing and gastrointestinal symptoms. A skin prick test was positive, indicating a type 1 hypersensitivity reaction. Deferoxamine desensitization was attempted with various differentprotocols. Finally, the patient could tolerate deferoxamine therapy at the dose previously administered. We proposed this modified subcutaneous desensitization protocolforpediatric cases that develop allergic reactions to deferoxamine.

Research paper thumbnail of Curative Stem Cell Transplantation for Severe Hb H Disease Manifesting From Early Infancy: Phenotypic and Genotypic Analyses

Hemoglobin, 2015

Most people with Hb H disease live normal lives; however, a minority of cases requires lifelong r... more Most people with Hb H disease live normal lives; however, a minority of cases requires lifelong regular transfusions. An atypical form of nondeletional Hb H disease was reported in a Thai boy, characterized by severe persistent hemolytic anemia since the age of 2 months. Molecular diagnosis revealed the apparent compound heterozygosity for the Southeast Asian (- -(SEA)) and α2 polyadenylation (polyA) signal (AATAAA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;AATA- -) deletions. The proband was successfully treated with allogeneic hematopoietic stem cell transplantation (HSCT). Accurate phenotypic and genotypic diagnosis in atypically severe Hb H disease is helpful for the understanding of its pathophysiology, the institution of appropriate management, and provision of genetic counseling and prenatal diagnosis. Hematopoietic stem cell transplantation is a potentially curative treatment option for this severe α-thalassemia (α-thal) syndrome.

Research paper thumbnail of Hemophagocytic lymphohistiocytosis

Research paper thumbnail of Modified desensitization protocols for a pediatric patient with anaphylactic reaction to deferoxamine

Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2014

Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload ... more Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload due to regular blood transfusions. Deferoxamine is used as chelating agentfor treatment ofpatients with chronic iron overload worldwide. Anaphylactic reaction to deferoxamine is rare, and the mechanism ofdeferoxamine-induced anaphylaxis is not well understood. Only afewpediatric cases ofsuccessful desensitization for deferoxamine hypersensitivity have been described, and a different protocol has been used in each report. We report a case ofanaphylaxis to deferoxamine in a thirteen-years-old Thai boy with Hemoglobin E/β-thalassemia disease who underwent successful desensitization. He had been receiving blood transfusions since the age often months. At age eleven, the patient began treatment with deferoxamine. Treatment was interrupted after the occurrence ofanaphylaxis, with urticaria, wheezing and gastrointestinal symptoms. A skin prick test was positive, indicating a type 1 hypersensiti...

Research paper thumbnail of Biopsychosocial predictors of health-related quality of life in children with thalassemia in Thammasat University Hospital

Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2010

To determine health-related quality of life (HRQOL) in children with thalassemia in order to expl... more To determine health-related quality of life (HRQOL) in children with thalassemia in order to explore physical and psychosocial factors affecting on their QOL. A cross-sectional study was conducted at Thammasat University Hospital, Pathum Thani. Sociodemographic factors and clinical characteristics were obtained from seventy-five of transfusion-dependent and non-transfused thalassemia patients. The PedsQL 4.0 Generic Core Scales (Thai version) were administered to determine the patients and their parents' perspectives. The mean (SD) of total HRQOL score was 78.50 (2.05) for children who were self-reporting and it was 73.41 (2.22) for parent proxy-report, that were comparable with population norms. The stepwise multiple regression analysis indicated that total HRQOL score of child self-report was negatively predicted by lower family income, early age onset of anemia before 2 years and under covered by Universal Health Coverage Scheme. The negative predictors of total HRQOL score o...

Research paper thumbnail of Challenges in the diagnosis and treatment of juvenile myelomonocytic leukaemia in Hong Kong over the past two decades

Hong Kong Journal of Paediatrics

Research paper thumbnail of Comparative outcomes of Thai children with acute lymphoblastic leukemia treated with two consecutive protocols: 11-year experience

Leukemia & Lymphoma, 2012

The aim of this study was to determine outcomes and prognostic features of children with acute ly... more The aim of this study was to determine outcomes and prognostic features of children with acute lymphoblastic leukemia (ALL) treated with two modified St Jude Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Research Hospital protocols at Ramathibodi Hospital (1997-2008). Event-free survival rates of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;previous protocol&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were 88.3 ± 3.3% and 83.0 ± 3.9% and of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;current protocol&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were 89.9 ± 3.4% and 88.0 ± 3.8%, at 3 and 5 years, respectively. Adverse prognostic features were identified only in the previous protocol study, including obesity, presenting leukocytes &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;100 × 10(9)/L, high-risk group, persistent blasts in a day-15 marrow and sepsis. Sepsis also conferred inferior overall survival rates of patients in both protocols. Steady improvement in cure rate over the past decade has clearly demonstrated the optimal use of treatment protocols and a multidisciplinary approach to implementing pediatric cancer care in Ramathibodi Hospital. Our future challenges are refinement in risk and treatment stratification and reduction of treatment-related toxicities, prioritizing death from infections.

Research paper thumbnail of Central Diabetes Insipidus

Journal of Pediatric Hematology/Oncology, 2013

Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syn... more Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

Research paper thumbnail of Impaired Glucose Tolerance and Insulin Resistance in Heart Failure: Underrecognized and Undertreated?

Journal of Cardiac Failure, 2010

A link between diabetes mellitus (DM) and heart failure (HF) has been well-recognized for more th... more A link between diabetes mellitus (DM) and heart failure (HF) has been well-recognized for more than a century. HF is also closely linked to abnormal glucose regulation (AGR) and insulin resistance (IR) in patients without DM and, similarly, these conditions commonly coexist. In epidemiological studies, each condition appears to predict the other. The prevalence of AGR/IR in HF patients without DM is significantly underrecognized and, as yet, the optimal method for screening for these abnormalities in the outpatient setting is unclear. The purpose of this review is to overview the prevalence and prognostic impact of AGR and IR in HF patients without DM and discuss potential pathophysiological pathways that link these conditions with HF. The severity of glucose intolerance in patients with HF correlates with functional and clinical severity of HF and is an independent predictor of an adverse outcome. It is thought that changes in cardiac metabolism, including a switch from glucose metabolism toward fatty acid metabolism, may in part contribute to the pathophysiological processes associated with HF patients with AGR/IR. We discuss how pharmacological targeting of metabolic pathways in the myocardium of these patients with HF may represent novel therapeutic strategies in these at-risk patients.

Research paper thumbnail of Widening Spectrum of Liver Angiosarcoma in Children

Objectives: Liver hemangiomas are vascular tumors, which occur in the first months of life and ca... more Objectives: Liver hemangiomas are vascular tumors, which occur in the first months of life and carry risks of initial complications, but are considered to be benign histologically and to regress with time. Histologic studies suggest that a subtype, type 2 hemangioendothelioma, is akin to angiosarcoma and may have a severe long-term prognosis. We report 5 girls with type 2 hemangioendothelioma of the liver. Methods and Results: Three children initially presented with classical infantile multinodular hemangioma, including cardiac and pulmonary complications and regression of tumors at age 1 1 /2 to 2 1 /2 years. All 3 experienced tumor relapse at ages 2 1 /2 to 3, leading to death at ages 2 1 /2 to 5. Tumor histology showed type 2 hemangioendothelioma. The other 2 children presented with liver tumors at ages 2 and 3 years. In 1, initial biopsy of a single tumor showed benign type 1 hemangioendothelioma, but surgical resection was followed by relapse in the remaining liver, lung metastases, and death. Whole tumor histology showed both type 1 and 2 lesions. In the other child, tumor biopsy showed type 2 lesions. She underwent liver transplantation and is alive without tumor recurrence 3 years later. Conclusions: Careful follow-up is necessary to detect late recurrence in infants with multinodular liver hemangiomas. Vascular liver tumors occurring after infancy are likely to be malignant. The high risk of relapse in the remaining liver suggests that if no metastases are detected, liver transplantation is preferable to surgical tumor resection in both situations.