Diagnostic and treatment strategies for pediatric acute lymphoblastic leukemia in low- and middle-income countries.

The survival rate of children and adolescents with acute lymphoblastic leukemia (ALL), the most common pediatric cancer, has improved significantly in high-income countries (HICs), serving as an excellent example of how humans can overcome catastrophic diseases. However, the outcomes in children with ALL in low- and middle-income countries (LMICs), where approximately 80% of the global population live, are suboptimal because of limited access to diagnostic procedures, chemotherapeutic agents, supportive care, and financial assistance. Although the implementation of therapeutic strategies in resource-limited countries could theoretically follow the same path of improvement as modeled in HICs, intensification of chemotherapy may simply result in increased toxicities. With the advent of genetic diagnosis, molecular targeted therapy, and immunotherapy, the management of ALL is changing dramatically in HICs. Multidisciplinary collaborations between institutions in LMICs and HICs will provide access to strategies that are suitable for institutions in LMICs, enabling them to minimize toxicities while improving outcomes. This article summarizes important aspects of the diagnosis and treatment of pediatric ALL that were mostly developed in HICs but that can be realistically implemented by institutions in countries with limited resources through resource-adapted multidisciplinary collaborations.

Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis.

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.

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.

Clinical Outcomes and Diagnostic Consistency of Serum and CSF Tumor Markers in Pediatric Intracranial Germ Cell Tumors in Thailand: A Multicenter Study.

The diagnostic and treatment outcomes of intracranial germ cell tumors (ICGCTs) among low and middle income countries are limited. A total of 63 ICGCTs patients with a median age of 11.6 years were studied. A 30 (47.6%) and 33 (52.4%) patients were classified as pure germinomas and nongerminomatous germ cell tumors (NGGCTs), respectively. The concordances between serum and cerebrospinal fluid (CSF) alpha-fetoprotein (84.3%) and beta-human chorionic gonadotropin (68.4%) were addressed. The 5-year overall survival (OS) and event-free survival (EFS) rates of pure germinomas versus NGGCTs were 83.9 versus 69.1% and 74.6 versus 57.7%, respectively. Patients undergoing radiation had higher 5-year OS and EFS than those without radiation treatment with P < .001. Chemotherapy combined with radiation is a cornerstone treatment to achieve outcomes. Adverse prognostic factors included age <8 years, surgery, and nonradiation treatment. Either serum or CSF tumor markers were adequately required as a diagnostic test among patients with ICGCTs.

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.

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.

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.

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.

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 outcomes and screening for organ involvement in pediatric Langerhans cell histiocytosis in Thailand: multicenter study on behalf of the Thai Pediatric Oncology Group.

Langerhans cell histiocytosis (LCH) is a rare disease across all age groups and is characterized by various degrees of severity and organ system involvement. A multi-institutional retrospective study of pediatric patients with LCH treated between 1999 and 2018 at five pediatric oncology centers was conducted to describe the clinical characteristics, prognostic factors, and outcomes of LCH and to validate screening tools for organ system involvement in pediatric LCH in Thailand. A total of 127 patients with a median age of 2.7 years were studied. The single-to-multisystem (MS) LCH ratio was 1:1. Forty-seven patients (71%) with MS-LCH had risk-organ involvement (RO +), whereas 19 (29%) patients had no risk-organ involvement (RO -). The 5-year overall and event-free survival rates were 91.3% and 73.6%, respectively, which were comparable to those in developed countries. Prognostic factors included age < 2 years, RO + MS-LCH, and number of RO + . Abnormal complete blood count was a highly sensitive indicator of bone marrow involvement. Plain radiography is an appropriate screening tool to detect bone involvement.

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.

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.

HBV Seroprotection and Anamnestic Response to Booster Vaccination in Pediatric Cancer Survivors.

Hepatitis B is a major global health concern and can be prevented in the era of vaccination. Impaired immunological memory to primary immunization is a common chemotherapy-related complication among cancer survivors. The study aimed to determine protective immunity against hepatitis B virus (HBV) and anamnestic response to booster vaccination. In all, 107 pediatric cancer survivors previously immunized with primary hepatitis B vaccination were enrolled. A hepatitis B booster dose was administered to those with suboptimal seroprotection (anti-HBs < 10 mIU/mL) and 2 additional doses were subsequently administered at 1 and 6 months to those whose anti-HBs remained low. Clinical and serologic parameters were analyzed. Sero-protective rate against HBV (anti-HBs ≥ 10 mIU/mL) among survivors was 20.6% with geometric mean titer (GMT) of 95.7 ± 265.6 mIU/mL. Anamnestic response was 61% after a booster vaccine among those with suboptimal seroprotection and 100% after 2 additional booster doses among those whose anti-HBs remained low. GMTs among those survivors after the First and third booster vaccines were 320.0 ± 412.4 mIU/mL and 826.5 ± 343.8 mIU/mL, respectively. Age at diagnosis was a significant independent risk factor for adequate seroprotection (adjusted OR = 0.84, 95%CI: 0.71-0.99) with a P-value of .034. No associated risk factors to predict optimal anamnestic response to booster vaccination were identified. Loss of immunological memory to primary hepatitis B immunization is an inevitable complication among most pediatric cancer survivors; therefore, assessing adequate seroprotection is essentially required. For those with limited accessibility to serologic tests, completion of full 3-booster-dose series is alternative and highly recommended.

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.

Serum Lactate: A Predictor of Septic Shock in Childhood Cancers with Febrile Neutropenia.

Early recognition and management are the key elements to prevent febrile neutropenia associated mortality. The prospective observational study aimed to investigate prognostic accuracy of serum lactate to predict septic shock within 48 hours among hemodynamically stable children with febrile neutropenia. In all, 99 pediatric oncology patients who developed febrile neutropenia were enrolled in the study. Clinical information during 48 hours and serum lactate at the time of enrollment were analyzed. Among 99 participating patients, 10 developed septic shock and 4 of those expired. No significant difference was found of patients' baseline characteristics and basic laboratory parameters between patients with and without septic shock. Serum lactate was significantly elevated among patients developing septic shock (P-value < .001) and those who expired (P-value .002). Receiver operating characteristic (ROC) curve was created to identify the best cutoff value for initial serum lactate associated with the development of septic shock within 48 hours. Baseline serum lactate more than 2.5 mmol/L showed the largest area under the ROC curve to predict the septic shock development within 48 hours (ROC area, 0.90; 95% confidence interval [CI], 0.81-0.98), with sensitivity, specificity, negative predictive value, and accuracy of 80.0%, 92.1%, 97.6%, and 90.9%, respectively. Serum lactate level determined early at the time of febrile neutropenia was an effective surrogate marker for developing septic shock within 48 hours among hemodynamically stable, pediatric oncology patients. The level more than 2.5 mmol/L was the best threshold to start preemptive aggressive hemodynamic monitoring and prompt treatment to ensure adequate tissue perfusion.

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 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 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.

Pediatric primary central nervous system tumors registry in Thailand under National Health Security Office schemes.

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.

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.