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.

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.

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.

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.

Unusual Case of Concurrent Retroperitoneal Congenital Infantile Fibrosarcoma and Cellular Type Congenital Mesoblastic Nephroma.

BACKGROUND: Although congenital infantile fibrosarcoma (cIFS) is a rare soft tissue sarcoma among children, it constitutes one of the most common soft tissue sarcomas during the first year of life. Congenital mesoblastic nephroma (CMN) is the most common benign renal tumor usually developing during the first 3 months of life. cIFS and cellular type CMN (cCMN) share not only similar histopathologic features but identical molecular genetic abnormality including the ETV6/NTRK3 fusion gene. Here, we report an unusual case of cIFS occurring with cCMN. CASE PRESENTATION: An 18-month-old girl presented with a 1-month history of abdominal distension and a few days' history of a palpable abdominal mass. A large heterogenous mass sized 9.0×11.2×11.6 cm on the right side of the abdomen and an isolated heterogenous lesion sized 4×4.5 cm within the right kidney were noted from the imaging study. Pathologic findings were consistent with cIFS and cCMN of the right kidney. In addition, both pathologic specimens contained the ETV6/NTRK3 fusion gene. CONCLUSION: Although cIFS and cCMN share similar histopathologic features and molecular genetic abnormality, simultaneous occurrence of these 2 types of tumor is exceedingly rare. To our knowledge, this is the first unusual case report of concurrent cIFS and cCMN.

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.

Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and CD56+ T cells in human blood.

Killer cell Ig-like receptors (KIRs) on NK cells have been linked to a wide spectrum of health conditions such as chronic infections, autoimmune diseases, pregnancy complications, cancers, and transplant failures. A small subset of effector memory T cells also expresses KIRs. In this study, we use modern analytic tools including genome-wide and multiplex molecular, phenotypic, and functional assays to characterize the KIR(+) T cells in human blood. We find that KIR(+) T cells primarily reside in the CD56(+) T population that is distinctively DNAM-1(high) with a genome-wide quiescent transcriptome, short telomere, and limited TCR excision circles. During CMV reactivation in bone marrow transplant recipients, KIR(+)CD56(+) T cells rapidly expanded in real-time but not KIR(+)CD56(-) T cells or KIR(+) NK cells. In CMV(+) asymptomatic donors, as much as 50% of CD56(+) T cells are KIR(+), and most are distinguishably KIR2DL2/3(+)NKG2C(+)CD57(+). Functionally, the KIR(+)CD56(+) T cell subset lyses cancer cells and CMVpp65-pulsed target cells in a dual KIR-dependent and TCR-dependent manner. Analysis of metabolic transcriptome confirms the immunological memory status of KIR(+)CD56(+) T cells in contrast to KIR(-)CD56(+) T cells that are more active in energy metabolism and effector differentiation. KIR(-)CD56(+) T cells have >25-fold higher level of expression of RORC than the KIR(+) counterpart and are a previously unknown producer of IL-13 rather than IL-17 in multiplex cytokine arrays. Our data provide fundamental insights into KIR(+) T cells biologically and clinically.

The clinical effect of fentanyl in comparison with ketamine in analgesic effect for oncology procedures in children: a randomized, double-blinded, crossover trial.

BACKGROUND: Children often require relief of pain and anxiety when undergoing painful procedures. OBJECTIVE: To determine the differences by comparing fentanyl and ketamine used in cancer-diagnosed children undergoing painful procedures. MATERIAL AND METHOD: A randomized, double-blinded, crossover trial was conducted with 55 children undergoing painful procedures (intrathecal chemotherapy and/or bone marrow aspiration/biopsy). Patients were randomly assigned in a double-blinded fashion to receive either intravenous fentanyl or ketamine at 1 mcg/kg/dose and 1 mg/kg/dose, respectively. The result in effectiveness of the drug was measured using three parameters, 1) satisfaction score ranging from 0 to 10, 2) perception of procedural pain using FLACC scale, Wong-Baker FACES Pain Rating Scale and Visual Analog Scale, and 3) the frequency of vomiting nausea score. RESULTS: The satisfaction amongpatients receiving fentanyl was significantly greater than ketamine (p = 0.007). In addition, both painful and nausea/vomiting were significantly decreased in the patients receiving fentanyl (p = 0.002 and p < 0.001, respectively). No serious complications were observed CONCLUSION: This study demonstrated that intravenous fentanyl generated a superior clinical effect in satisfaction, decreased pain and nausea/vomiting, and showed no significant side-effects over ketamine. Fentanyl may also be recommended as a reasonable option before undergoing oncology procedures in children with cancer.

Isolated Ocular Relapse in Childhood Acute Lymphoblastic Leukemia during Second Interim Maintenance Phase of Chemotherapy: Case Report.

More than 80% of acute lymphoblastic leukemia (ALL) in pediatric population is curable by using combinations of chemotherapy. However, 20% of the cases still suffer from disease relapse. The most common site of relapse is bone marrow. Relapse of childhood ALL involving the eyeball is rare. However, it occurs in 2.2% of relapsing children. The authors described a 10-year-old Thai boy with underlying ALL on therapy, presented with a one-month history of progressive visual loss of his right eye. The clinical and imaging studies strongly suggested the diagnosis of isolated ocular relapse. In this report, the authors presented the findings from successfully specific treatment consisting of systemic chemotherapy and radiation therapy on the affected eye. From other studies, the outcome was more favorable in cases of ocular relapse off therapy. In our study, one case of isolated ocular relapse ALL was reported.

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

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

Pediatric acute leukemia: the effect of prognostic factors on clinical outcomes at Phramongkutklao Hospital, Bangkok, Thailand.

BACKGROUND: Leukemia is the most common malignancy in children. Multiple prognostic factors have been used in order to assist the clinician to decide appropriate risk-adjusted treatment for each patient; the current clinical outcomes of those patients have been significantly improved over the past decades. OBJECTIVE: The purpose of this study was to examine survival outcome in children who were diagnosed with acute leukemia and treated in the Department of Pediatrics, Phramongkutklao Hospital during January 1, 2000 and July 31, 2013. MATERIAL AND METHOD: The authors retrospectively reviewed the patients who were diagnosed with acute leukemia and treated at Phramongkutklao Hospital. Their clinical data were collected and analyzed based on clinicalfeatures inchluding age, initial WBC count at diagnosis, sex, immnunophenotype and cytogenetic abnormalities. RESULTS: Total 152 patients with acute leukemia, 123 patients were diagnosed with acute lymnphoblastic leukemia (ALL) and 29 patients were diagnosed with acute myeloid leukemia (AML). The 5-year survival rates of ALL and AML patients were 72.63% and 30.30%, respectively. In addition, we found a correlation between the ALL patients' clinical outcomes and several prognostic factors including initial white blood cell count, CNS status at diagnosis and ploidy. However, there was no correlation between those factors and clinical outcomes in AML patients. CONCLUSION: Our treatment outcomes on patients with acute leukemia were similar to the reports from other countries. The several prognostic factors especially initial WBC at diagnosis can assist the clinician to select appropriate treatment option for each patient.

The factors of ketamine that affect sedation in children with oncology procedures: parent satisfaction perspective.

BACKGROUND: The pain and its complication during sedation with ketamine remain a significant problem for children with hematologic malignancy. OBJECTIVE: The purpose of the present study was to evaluate further the parental satisfaction for procedural sedation and analgesia during pediatric hematology/oncology procedures perfonned by pediatrician in the Department of Pediatrics, Phramongkutklao Hospital. MATERIAL AND METHOD: The authors prospectively evaluated our experience using intravenous ketamine 1 mg/kg for oncology patients undergoing procedures at Department ofPediatrics, Phramongkutklao Hospital. The procedure was assessed by way ofaphysician-completed form and by evaluation of questionnaires given to parents to estimate levels of pain by using a 0 to 10 mm visual analog scale (VAS) at 2 hours after procedures and results in any adverse events with respect to age, gende, procedures performed, ketamine dosage and recovery time. RESULTS: Total of46 children aged 6 months to 15 years with 46procedures were observed at pediatric unit post-procedure. The indicationsfor procedural sedation and analgesia included lumbar puncture and intrathecal chemotherapy (50%), bone marrow aspiration or biopsy (21.7%), and both plrocedures (28.3%). The median VAS scale during oncology procedures was 3, which were expressed by all the parents/guardians of the children treated. Adverse effects were observed in all children including nausea (30.4%), hypersalivation (26.1%), vomiting (21.7%), hallucinlation (4.2%). No child required admission to hospital and there were no serious complications. CONCLUSION: hntravenous ketamine 1 mg/kg is effective for invasive procedures in children with malignancy. The use of intravenous ketamine may produce psychedelic effects in children. These adverse effects may alter the child's comfort and parental satisfaction especially in the young children.

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.

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

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

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.