Health-related quality of life and its determinant factors in Thai children with cancer: parents vs. children perspectives.

BACKGROUND: Health-related quality of life (HRQOL) is a vital assessment to demonstrate the achievement in pediatric cancer care parallels that of medical treatment. The Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module in the Thai Version has become a standard tool to access the HRQOL among Thai children with cancer and their families. This study aimed to explore the HRQOL and factors related to HRQOL among pediatric oncology patients using the PedsQL 3.0 Cancer Module. METHODS: In 2018-2019, a single-institution, cross-sectional study was conducted among children with cancer and their families in Bangkok, Thailand. A paired-sample t-test was performed to evaluate the differences between the HRQOL scores of the child and parents' reports. Linear regression was used to evaluate factors associated with HRQOL and which particular domains of the PedsQL 3.0 Cancer Module were influenced. RESULTS: Eighty-five children with cancer and their families were enrolled. The patients' mean age was 10.82 ± 5.48 years. The most common cancer types included acute lymphoblastic leukemia (n = 32, 67%), central nervous system tumors (n = 13, 15%), osteosarcoma (n = 10, 27%) and neuroblastoma (n = 9, 24%), in rank. The mean HRQOL scores in child and parent reports were 74.37 ± 15.7 and 70.42 ± 17.15, respectively (p = 0.034). Factors negatively correlated to HRQOL in parent reports were the number of outpatient visits (p = 0.019) and hospital admissions (p = 0.002). The number of hospitalizations was the only independent factor that affected HRQOL (p = 0.044). The number of outpatient visits and/or hospital admissions was influenced by pain and hurt, nausea, procedural anxiety and communication domains (p < 0.05). Only the number of hospitalizations was an independent factor influencing the procedural anxiety domain in HRQOL (p = 0.005). CONCLUSION: HRQOL among Thai children with cancer was desirable from both children's and parent's perspectives. Differences between child and parent HRQOL scores were observed. The number of outpatient visits and hospital admissions affected HRQOL, particularly in the procedural anxiety aspect. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR) Number: TCTR20200904001 (04/09/2020),  https://www.thaiclinicaltrials.org/ .

Improving comprehension, recall and attention using multimedia-informed assent among pediatric oncology patients: A comparative randomized controlled trial.

BACKGROUND: Assent should be obtained in all children involved in research in keeping with their level of maturity. Traditional assent forms contain too much information and are difficult to read. The study aimed to identify an effective tool to enhance children's comprehension during the assent process and focused on those with cancer who are likely more engaged in research involving greater than minimal risk. METHODS: In all, 116 children with cancer were randomized to receive either a paper-based assent document or a multimedia-based assent document. Open-ended and multiple-choice questions were used to assess comprehension and recall. Time spent on the documents and children's behavior during the assent process was recorded to determine their attention and satisfaction. RESULTS: Children randomized to a multimedia-based assent document achieved significant higher comprehension and recall assessment scores (p-values <.001). The high score achievement significantly correlated with the child's age with adjusted odds ratio (OR) of 1.90 (p-value <.001; 95% confidence interval [CI]: 1.35-2.66) for comprehension assessment and 1.59 (p-value .001; 95% CI: 1.20-2.12) for recall assessment. Children randomized to a multimedia-based assent document had significant longer time spent on the document (p-value .001) with less numbers of inattention (p-value <.001) and expressed more signs of enjoyment during the assent process (p-values <.001). CONCLUSION: Multimedia-based assent document successfully enhanced comprehension, recall, and attention with more satisfaction compared with a traditional paper-based document among children with cancer. This approach may be considered as an alternative format for children engaging in research involving greater than minimal risk.

Treatment outcomes among high-risk neuroblastoma patients receiving non-immunotherapy regimen: Multicenter study on behalf of the Thai Pediatric Oncology Group.

BACKGROUND: Neuroblastoma is the most common extracranial malignant solid tumor during childhood. Despite intensified treatment, patients with high-risk neuroblastoma (HR-NBL) still carry a dismal prognosis. The Thai Pediatric Oncology Group (ThaiPOG) proposed the use of a multimodality treatment to improve outcomes of HR-NBL in non-immunotherapy settings. METHODS: Patients with HR-NBL undergoing ThaiPOG protocols (ThaiPOG-NB-13HR or -18HR) between 2013 and 2019 were retrospectively reviewed. Patient demographic data, treatment modalities, outcomes, and prognostic factors were evaluated and analyzed. RESULTS: A total of 183 patients with HR-NBL undergoing a topotecan containing induction regimen were enrolled in this study. During the consolidation phase (n = 169), 116 patients (68.6%) received conventional chemotherapy, while 53 patients (31.4%) underwent hematopoietic stem cell transplantation (HSCT). The 5-year overall survival (OS) and event-free survival (EFS) were 41.2% and 22.8%, respectively. Patients who underwent HSCT had more superior 5-year EFS (36%) than those who received chemotherapy (17.1%) (p = .041), although they both performed similarly in 5-year OS (48.7% vs. 39.8%, p = .17). The variation of survival outcomes was observed depending on the number of treatment modalities. HSCT combined with metaiodobenzylguanidine (MIBG) treatment and maintenance with 13-cis-retinoic acid (cis-RA) demonstrated a desirable 5-year OS and EFS of 65.6% and 58.3%, respectively. Poorly or undifferentiated tumor histology and cis-RA administration were independent factors associated with relapse and survival outcomes, respectively (p < .05). CONCLUSION: A combination of HSCT and cis-RA successfully improved the outcomes of patients with HR-NBL in immunotherapy inaccessible settings.

Impact of treatment refusal and abandonment on survival outcomes in pediatric osteosarcoma in Southeast Asia: A multicenter study.

BACKGROUND: Treatment refusal and abandonment (TxRA) are major barriers to improving outcomes among children with sarcomas of the extremities as curative treatment options bearing on amputation or disfiguring surgery, particularly in countries with limited resources. A multi-institutional retrospective study was conducted to determine the predictive factors for TxRA among patients with osteosarcoma associated with survival outcomes across Southeast Asia (SEA). METHODS: Pediatric patients with osteosarcoma treated between January 1998 and December 2017 in four SEA pediatric oncology centers from three countries were studied. Nelson-Aalen estimates, Kaplan-Meier method, and Cox's proportion hazard model were applied to address the cumulative incidence, survival outcomes, and to identify prognostic factors associated with TxRA. RESULTS: From a total of 208 patients with osteosarcoma enrolled; 18 (8.7%) patients refused and 41 (19.7%) patients abandoned treatment. Income classification of countries, age at diagnosis, tumor size, disease extent, chemotherapy protocols, and types of surgery were associated with TxRA. Tumor size more than 15 cm was an independent risk factor associated with TxRA. The 5-year overall and relapse-free survivals were 49.4% and 50.4%, respectively. However, these rates declined further to 37.9% and 35.8%, respectively, when TxRA were considered as events. Tumor size larger than 15 cm and metastatic disease were independent risk factors associated with TxRA-sensitive outcomes. CONCLUSION: The prevalence of TxRA was high in SEA, particularly in lower middle-income countries. Factors associated with TxRA related to tumor burden. Treatment outcomes could be substantially improved by lowering the refusal and abandonment rates.

The efficacy and safety of midazolam with fentanyl versus midazolam with ketamine for bedside invasive procedural sedation in pediatric oncology patients: A randomized, double-blinded, crossover trial.

Children with cancer often require sedation before undergoing invasive procedures. Fentanyl, ketamine, and midazolam are effective drugs widely used for procedural sedation. This study aimed to investigate the efficacy and safety of midazolam-fentanyl (M-F) compared with midazolam-ketamine (M-K) for bedside procedural sedation among pediatric oncology patients. A randomized, double-blinded, crossover trial was conducted among children with cancer requiring procedural sedation for invasive procedures. Patients were randomly assigned either intravenous M-F or M-K and subsequently received the alternate regimens following the crossover design of the study. The efficacy and safety of the sedations including sedation time intervals, nausea score, vomiting episodes, pain score, adverse effects, and parent's satisfaction were evaluated. In all, 58 patients with 116 procedural sedations were enrolled. M-K provided a shorter induction time (0:58 vs. 1:23 min) (p = 0.005), but longer sedation (9:02 vs. 5:50 min) (p = 0.019) and emergence time (4:26 vs. 0:56 min) (p = 0.011) compared with M-F. Sedation routes affected the sedation time intervals. Patients had higher rates of vomiting (0, range 0-8 vs. 0, range 0-2) (p = 0.033) but experienced less pain (0 vs. 2) (p = 0.008) in the M-K group. Overall satisfaction and other adverse effects were comparable among both sedation regimens. Combined sedative drugs are recommended to improve the effectiveness of bedside procedural sedation. M-K provided shorter induction, but longer sedation and emergence time compared with M-F. These findings correlated with sedative routes. Patients receiving M-K experienced a higher rate of vomiting, but less painfulness compared with M-F. Overall satisfaction and tolerable side effects were comparable among both sedative regimens.

Single daily dosing versus divided dosing intravenous ondansetron to prevent chemotherapy-induced nausea and vomiting among children: A comparative randomized double-blind controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common complication in cancer treatment. Ondansetron is an effective antiemetic drug widely used to prevent CINV; however, the effective administrative dosing strategies among pediatrics remain unclear. The study aimed to investigate clinical effectiveness of single daily dosing versus divided dosing ondansetron. METHODS: In all, 194 children undergoing chemotherapy were randomized to receive either single daily dosing (0.3 mg/kg/dose) or divided dosing (0.15 mg/kg/dose every 8 hours) intravenous ondansetron for 24 hours. Clinical parameters including number of emesis episodes, nausea scores, appetite levels, parent's satisfaction, and adverse effects within 24 hours were analyzed. RESULTS: No significant differences were found between the two dosing strategies concerning number of emesis episodes and parent's satisfaction. However, nonleukemic hematologic malignancies and concurrent administration of intrathecal methotrexate-hydrocortisone-cytarabine (IT-MHA) were associated with increased risk of acute-phase vomiting. Interestingly, none of the patients aged under 7 years, receiving divided dosing ondansetron, presented nausea symptoms compared with those receiving single daily dosing (p-value .034). No significant differences regarding headache were observed between the two dosing strategies and none of the patients experienced QTc prolongation. CONCLUSION: Ondansetron administered as divided dosing should be considered among children aged under 7 years to prevent chemotherapy-induced nausea and among patients receiving low emetogenic chemotherapy to maintain their appetite. Both administrative dosing strategies were well tolerated with no significant adverse effects.

Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study.

BACKGROUND: Neuroblastoma is the most common extra-cranial solid tumor among children. Despite intensive treatment, patients with advanced disease mostly experience dismal outcomes. Here, we proposed the use of topotecan and cyclophosphamide containing induction regimen as an upfront therapy to high risk neuroblastoma patients. METHODS: Patients with high risk neuroblastoma undergoing ThaiPOG high risk neuroblastoma protocol from 2016 to 2017 were studied. All patients received 6 cycles of induction regimen consisting of 2 cycles topotecan (1.2 mg/m2/day) and cyclophosphamide (400 mg/m2/day) for 5 days followed by cisplatin (50 mg/m2/day) for 4 days combined with etoposide (200 mg/m2/day) for 3 days on the third and fifth cycles and cyclophosphamide (2100 mg/m2/day) for 2 days combined with doxorubicin (25 mg/m2/day) and vincristine (0.67 mg/m2/day) for 3 days on the fourth and sixth cycles. Treatment response after the 5th cycle before surgery and treatment-related toxicities after each topotecan containing induction cycle were evaluated. Relevant prognostic factors were analyzed to measure the treatment response among those patients. RESULTS: In all, 107 high risk neuroblastoma patients were enrolled in the study. After the 5th cycle of induction regimen, the patients achieved complete response (N = 2), very good partial response (N = 40), partial response (N = 46) and mixed response (N = 19). None of the patients experienced stable disease or disease progression. The most significant prognostic factor was type of healthcare system. The most common adverse effect was febrile neutropenia followed by mucositis, diarrhea and elevated renal function. CONCLUSION: The topotecan and cyclophosphamide containing induction regimen effectively provides favorable treatment response. The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.

Molecular Characterization of Hb H and AEBart's Diseases in Thai Children: Phramongkutklao Hospital Experiences.

Background: Alpha-thalassemia is a common genetic disorder in Thailand and is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes Hb H disease and interaction of Hb H disease with heterozygous Hb E results in AEBart's disease. Objective: The present study aimed to characterize the genotype of α-globin gene in 81 pediatric patients with Hb H and AEBart's diseases in Phramongkutklao Hospital, a tertiary care center for thalassemic patients in central Thailand. Material and Method: Eighty one unrelated pediatric patients including 60 patients with Hb H disease and 21 patients with AEBart's disease were enrolled in our study. Mutation analysis was performed by multiplex gap-PCR, multiplex-ARMS and direct DNA sequencing of both HBA1 and HBA2 genes, respectively. Results: A total of 81 pediatric patients with Hb H and AEBart's diseases who mainly lived in central Thailand were included in the present study. Eight different α-thalassemia mutations interacting to produce seven genotypes of α-globin gene in both Hb H and AEBart's diseases were identified. The number of patients in the non-deletional form was higher than in the deletional form for both Hb H (51.6% VS 48.4%) and AEBart's diseases (52.4% VS 47.6%). The SEA deletion (--SEA) was the most common (98.8%) α-thalassemia 1 mutation. While 3.7-kb deletion (-α3.7) was the most common (90%) α-thalassemia 2 deletion, Hb CS was the most common (90%) non-deletional a-thalassemia 2. Uncommon non-deletional α-thalassemia 2 mutation identified in our study were Hb QS, Hb PS and initiation codon mutation, respectively. Conclusion: All of the α-thalassemia mutation in our pediatric patients with Hb H and AEBart's diseases have been characterized by the combination of molecular techniques including multiplex gap-PCR, multiplex-ARMS and DNA sequencing of HBA1 and HBA2 genes.

Pediatric hemophagocytic lymphohistiocytosis in a tropical country: Results of a multicenter study in Thailand.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition caused by genetic mutation or various triggers disturbing the immune system. METHODS: A multicenter retrospective study of pediatric patients with HLH receiving a diagnosis between January 2005 and December 2019 from three pediatric oncology centers was conducted to explore the clinical characteristics and determine prognostic factors associated with outcomes among Thai children. RESULTS: In all, 78 patients with HLH with a median age at diagnosis of 3.17 (range, .08-17.83) years were enrolled. The male to female ratio was 1.2:1. The most common type of HLH was infection-associated hemophagocytic syndrome (IAHS) (n = 59, 75%) of which Epstein-Barr virus was the most common pathogen. Thrombocytopenia, hyperbilirubinemia, and treatment response at weeks 2 and 8 after initiating treatment were associated with mortality. Platelet count <50,000 cells/mm3 was the only independent prognostic factor to define survival outcome (p-value .035). Two-year overall survival rate was 71.3% (95% confidence interval, 59.2%-80.3%). Survival rates between IAHS, malignant associated HLH, macrophage activation syndrome, and unspecific HLH did not significantly differ (p-value .571). CONCLUSION: IAHS was the most common cause among pediatric HLH in Thailand. The outcomes of Thai children with HLH were comparable to those of developed countries. Platelet count <50,000 cells/mm3 was the only independent prognostic factor to define survival outcome.

The Reliability of the Thai version of Health-Related Quality of Life Questionnaire: PedsQL 3.0 Cancer Module.

Assessing the health-related quality of life (HRQOL) is highly recommended as a standard of care for children with cancer in conjunction with medical treatment. The Pediatric Quality of Life Inventory (PedsQL) Cancer Module is a standard tool designed to assess the HRQOL among pediatric oncology patients. This study aimed to evaluate the reliability and correlation of the PedsQL 3.0 Cancer Module in Thai version between child and parent reports. A cross-sectional study was conducted on 85 Thai children with cancer and their families. Excellent internal consistency of the PedsQL 3.0 Cancer Module of the Thai version was addressed among child and parent reports (0.92 and 0.94, respectively). Overall positive correlations were also found between child and parent reports (r = 0.61, P < .001). However, the statistically significant differences of HRQOL scores between child and parent reports were determined on procedural anxiety (70.05 ± 26.67 vs 60.03 ± 25.6, P = .003), treatment anxiety (88.15 ± 17.37 vs 76.82 ± 26.7, P = .001), worry (66.67 ± 25.59 vs 55.34 ± 30.37, P = .003) and the total score (74.37 ± 15.7 vs 70.42 ± 17.15, P = .034). This study demonstrated desirable internal reliability with positive correlations between child and parent reports of the PedsQL 3.0 Cancer Module in Thai version, although possible differences between child and parent HRQOL scores should be considered.

Predictors and Treatment Outcomes of Pediatric Osteosarcoma in Diverse Socioeconomic Backgrounds in Southeast Asia: A Retrospective Multicenter Study.

BACKGROUND: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA. METHODS: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan-Meier method and Cox's Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors. RESULTS: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome.  Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.

Clinical characteristics and outcomes of Langerhans cell histiocytosis at a single institution in Thailand: a 20-year retrospective study.

Background: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the various systems involved and clinical manifestations with a wide range of symptoms. Objectives: To describe clinical characteristics, imaging, treatment, and outcomes of pediatric LCH at Phramongkutklao Hospital, Bangkok, Thailand. Methods: We conducted a 20-year retrospective review of the medical records of patients diagnosed with LCH from birth to 21 years old from January 1, 1997, to December 31, 2016. Results: In all, 14 patients with median age of 2.5 years were studied. Six (43%) patients had single-system (SS) LCH. Five patients (63%) with multisystem (MS) LCH (n = 8. 57%) had risk-organ involvement (RO+). All patients had plain X-ray imaging of their skull with 11 (79%) showing abnormal findings. Tc-99m bone imaging and fluorodeoxyglucose F18 (FDG) positron emission tomography (PET)-computed tomography (CT) demonstrated abnormal findings in 8 (89%) and 4 (29%) patients, respectively. The 5-year event-free survival (EFS) for patients with RO+ MS-LCH was less than that for those without risk-organ involvement (RO-) MS-LCH and SS-LCH (20% vs. 100%, P = 0.005). Hematological dysfunction, hypoalbuminemia, and conjugated hyperbilirubinemia may be worse prognostic factors for RO+ MS-LCH. Conclusion: FDG-PET-CT might have a greater accuracy to detect LCH disease than conventional plain X-ray and Tc-99m bone imaging. RO+ MS-LCH has been encountered with relapse and poor outcomes. Hematopoietic involvement, hypoalbuminemia, and conjugated hyperbilirubinemia may be worse prognostic factors for RO+ MS-LCH.

Clinical Characteristics and Predictive Factors of Invasive Fungal Disease in Pediatric Oncology Patients with Febrile Neutropenia in a Country with Limited Resources.

BACKGROUND: The most common complication among pediatric oncology patients is febrile neutropenia (FN). Invasive fungal disease (IFD) is suspected when fever persists >4-7 days after empirical antibiotics. Its clinical characteristics and predictive factors associated with IFD among pediatric oncology patients with FN were thus explored. METHODS: Pediatric oncology patients with FN between January 1, 2012 and December 31, 2016 were enrolled in this study. Clinical characteristics, including laboratory investigations, treatment modalities, and final outcomes of IFD were retrospectively reviewed and analyzed. RESULTS: In all, 73 patients with 180 episodes of confirmed diagnosis of FN were studied. Median age at diagnosis was 6.2 years, with equal sex distribution. The most common diagnosis was acute lymphoblastic leukemia (n=91, 51%), followed by acute myeloid leukemia (n=47, 26%), Burkitt's lymphoma (n=7, 4%) and neuroblastoma (n=7, 4%). Median absolute neutrophil count at FN diagnosis was 0 (0-806) cells/mm3. IFD was diagnosed for 25 (14%) episodes. Mortality rates for FN and IFD were 4% and 20%, respectively. Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results, and prolonged broad-spectrum antibiotic administration were factors associated with IFD (P<0.05). Prolonged duration between initiation of fever and antifungal administration for nearly 10 days was an independent factor in prediction of IFD occurrence (P=0.014). CONCLUSION: Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results and prolonged broad-spectrum antibiotic administration were factors associated with IFD. Duration between initiation of fever and antifungal administration of nearly 10 days were considered a risk factors of IFD among patients with FN. IRB REFERENCE NUMBER: IRBRTA 825/2560.

ITPA:c.94C>A and NUDT15:c.415C>T Polymorphisms and Their Relation to Mercaptopurine-Related Myelotoxicity in Childhood Leukemia in Thailand.

BACKGROUND: Mercaptopurine is a key agent in childhood leukemia treatment. Genetic polymorphism in the genes involving thiopurine metabolisms is related to 6-MP related toxicity. OBJECTIVE: This study aimed to determine the prevalence of ITPA:c.94C>A and NUDT15:c.415C>T polymorphisms among Thai children diagnosed with leukemia and their association with mercaptopurine-related myelotoxicity. METHODS: Patients and survivors with a diagnosis of leukemia treated with mercaptopurine-containing chemotherapy regimens were enrolled. Clinical data and laboratory parameters during treatment as well as ITPA:c.94C>A and NUDT15:c.415C>T genotypes were analyzed. RESULTS: In all, 99 patients with acute leukemia or survivors were enrolled in the study. The prevalences of ITPA:c.94C>A, NUDT15:c.415C>T, and co-occurrence of ITPA:c.94C>A and NUDT15:c.415C>T polymorphisms were 34, 17, and 4%, respectively. Numbers of absolute neutrophil count (ANC) and platelet count significantly decreased among patients carrying NUDT15:c.415C>T compared with NUDT15 wild type patients with p-values<0.001 and 0.019, respectively. The differences were not observed among patients carrying ITPA:c.94C>A compared with ITPA wild type patients. According to multivariate GEE, NUDT15:c.415C>T and co-occurrence of ITPA:c.94C>A and NUDT15:c.415C>T had a significant negative effect on ANC during treatment (coefficient: -463.81; CI: -778.53, -149.09; p-value=0.004 and coefficient: -527.56; CI: -1045.65, -9.48; p-value=0.046). No significant effect of ITPA:c.94C>A on ANC during treatment was observed. CONCLUSION: ITPA:c.94C>A and NUDT15:c.415C>T polymorphisms are common among Thai children with leukemia. A strong association with mercaptopurine-related myelotoxicity was observed among patients carrying either NUDT15:c.415C>T alone or combined with ITPA:c.94C>A.

Clinical Characteristics and Prognostic Factors in Pediatric Vascular Tumors.

BACKGROUND: The most common type of vascular tumors reported among children is hemangioma. The determinant factors to predict clinical outcomes among those patients were not well studied. OBJECTIVE: The study aimed to explore clinical characteristics and treatment approaches as well as associated prognostic factors of vascular tumors specifically in a pediatric population. METHODS: Pediatric patients with a confirmed diagnosis of vascular tumors between January 1, 2005 and December 31, 2017 were enrolled in this study. Clinical data includes initial clinical manifestations with associated complications, and diagnostic studies were used. To establish a diagnosis, the treatment modalities provided and final outcomes were retrospectively reviewed and analyzed. RESULTS: In all, 50 patients with a confirmed diagnosis of vascular tumors were enrolled. The median age at diagnosis was 11.5 years with equal gender distribution. The most common type of vascular tumor was hemangioma (n=41, 82%), followed by pyogenic granuloma (n=4, 8%), kapasiform hemangioendothelioma with Kasabach-Merritt phenomenon (n=2, 4%), infantile hepatic hemangioma (n=2, 4%), and juvenile nasal angiofibroma (n=1, 2%). The median age at diagnosis among patients with cutaneous vascular tumors (12.4 years) was significantly older than the age of those with visceral vascular tumors (1.3 years) witha P-value of 0.009. The mean size among patients with visceral tumors (7.46±4.84 cm) was significantly greater than the size among patients with cutaneous tumors (3.21±3.7 cm) with a P-value of 0.023. The size of the tumor was the only independent risk factor associated with clinical outcomes. CONCLUSION: Age at diagnosis in cutaneous vascular tumors was significantly older than in visceral vascular tumors. Clinical outcomes are favorable among most patients and the size of the tumors is an independent risk factor associated with outcomes.

Clinical Usefulness of Furosemide to Prevent Volume Overload Among Children and Young Adults with Transfusion-Dependent Thalassemia: A Randomized, Open-Label, Crossover Study.

PURPOSE: Red blood cell transfusion is a key element of treatment among patients with transfusion-dependent thalassemia (TDT). Volume overload and HCC syndrome (hypertension, convulsion, and intracranial hemorrhage) are fatal complications related to transfusion. Furosemide has been widely used to prevent hypertension secondary to volume overload with unclear supportive evidence. This study aimed to evaluate the efficacy of furosemide to prevent volume overload among children and young adults diagnosed with TDT. METHODS: Patients diagnosed with TDT were enrolled and randomized to receive either furosemide pretransfusion or no furosemide pretransfusion. After 3 weeks to 4 months of wash-out periods, those patients underwent the alternate regimens as per crossover design of the study. Clinical and laboratory parameters including blood pressure and NT-proBNP levels were measured before and after each transfusion. The difference of those parameters between two randomized groups and their potential associated factors were analyzed. RESULTS: In all, 30 patients undergoing 60 red blood cell transfusions were enrolled in the study. All were randomized and crossover was designed as receiving and not receiving furosemide pretransfusion. No transfusion reactions, symptoms of volume overload and HCC syndrome were observed. No statistically significant correlation was found between pretransfusion furosemide and the difference between pre- and posttransfusion systolic blood pressure (2 mmHg systolic blood pressure difference in pretransfusion furosemide and 1.5 mmHg in no pretransfusion furosemide; p-value = 0.721), as well as between pretransfusion furosemide and the difference between pre- and posttransfusion NT-proBNP levels (-3.8 pg/mL NT-proBNP level difference in pretransfusion furosemide and -2.4 pg/mL in no pretransfusion furosemide; p-value = 0.490). No significant correlation was also observed even in selected patients with high NT-proBNP levels (p-value = 0.262). Associated factors affecting the difference between pre- and posttransfusion NT-proBNP levels were analyzed, and none of those were affected concerning the difference in the levels. CONCLUSION: Furosemide has been included in standard transfusion guidelines in many institutions. Our study provided important evidence of the unnecessary use of the drug in preventing volume overload particularly in pediatric and young adult patients with TDT. THAI CLINICAL TRIALS REGISTRY TCTR NUMBER: TCTR20180209001. Registered 6 February 2018, https://www.clinicaltrials.in.th/.

Clinical and molecular genetic features of Hb H and AE Bart's diseases in central Thai children.

BACKGROUND: α-Thalassemia, one of the major thalassemia types in Thailand, is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes hemoglobin H (Hb H) disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb E) results in AE Bart's disease. OBJECTIVE: This study aimed to characterize the clinical and hematological manifestations of 76 pediatric patients with Hb H and AE Bart's diseases treated at Phramongkutklao Hospital, a tertiary care center for thalassemia patients in central Thailand. PATIENTS AND METHODS: Seventy-six unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with AE Bart's disease, were enrolled in this study. Their clinical presentations, transfusion requirement, laboratory findings, and mutation analysis were retrospectively reviewed and analyzed. RESULTS: A total of 76 pediatric patients with Hb H and AE Bart's diseases who mainly lived in central Thailand were included in this study. The clinical severities of patients with non-deletional mutations were more severe than those with deletional mutations. Eighty-six percent of patients with non-deletional AE Bart's disease required more blood transfusion compared to 12.5% of patients with deletional AE Bart's disease. Non-deletional AE Bart's disease also had a history of urgent blood transfusion with the average of 6±0.9 times compared to 1±0.3 times in patients with deletional Hb H disease. The difference was statistically significant. CONCLUSION: This study revealed the differences in clinical spectrum between patients with Hb H disease and those with AE Bart's disease in central Thailand. The differentiation of α-thalassemia is essential for appropriate management of patients. The molecular diagnosis is useful for diagnostic confirmation and genotype-phenotype correlation.