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.

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.

Impaired glucose tolerance and insulin resistance in survivors of childhood acute lymphoblastic leukemia: prevalence and risk factors.

AIM/PURPOSE: Survivors of acute lymphoblastic leukemia (ALL) are at increased risks of impaired glucose metabolism, insulin resistance, and metabolic syndrome. The aim of our study was to determine the prevalence of alterations in glucose metabolism and the predisposing factors of these disturbances in survivors of childhood ALL. PATIENTS AND METHODS: In 131 ALL survivors, an oral glucose tolerance test was conducted to determine beta-cell function/insulin sensitivity. The particular risk factors were analyzed and 6 single nucleotide polymorphisms of diabetic predisposing genes: PAX4 and TCF7L2 were genotyped to evaluate the association between these factors and beta-cell function/insulin sensitivity. RESULTS: Ten out of 131 survivors (7.6%) had impaired glucose tolerance (IGT) whereas 40 out of 131 (30.5%) had insulin resistance (IR) and showed characteristics of the metabolic syndrome (hyperinsulinemia, hypertriglyceridemia, and low HDL-C). In the logistic regression analysis, the most important factor predicting IGT and IR was older age of survivors (P=0.014 and P<0.001, respectively) whereas the PAX4 R192H mutation (rs2233580) was significantly associated with IGT after adjustment for age (P=0.043) (adjusted OR 5.28, 95% CI 1.06-26.40). CONCLUSIONS: Existing evidence suggests that older age is an independent risk factor for developing IGT and IR in childhood ALL survivors, emphasizing the need for life-long metabolic screening. The PAX4 variant might impact individual susceptibility against IGT and diabetes. However, an identification of underlying risk(s) is the rational for future studies.

Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial.

OBJECTIVE: To investigate the effect of Helicobacter pylori eradication on platelet recovery in childhood chronic idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: A multi-center randomized controlled trial was conducted. Patients aged 4-18 years, diagnosed with chronic ITP, defined by platelet count below 100 x 10(9)/L lasting more than 6 months without identified causes, were enrolled and underwent (13)C-urea breath test for diagnosis of H. pylori infection. Patients who received prednisolone more than 0.5 mg/kg per day or received other platelet-enhancing therapy were excluded. Patients with H. pylori infection were randomized into two groups: treatment and control groups. Treatment group received a standard protocol for H. pylori eradication and repeated (13)C-UBT at 4-6 weeks to confirm successful therapy while the control group received no specific treatment. Monthly platelet count was monitored for 6 months in both groups. Primary outcome was platelet recovery, defined by platelet count over 100 x 10(9)/L for at least 3 months. RESULTS: Of the 55 ITP children, 16 (29.1%) had H. pylori infection. There were no differences in age, sex, duration of disease, platelet count, and the dose of prednisolone between the treatment group (n = 7) and control group (n = 9). One patient in control group was withdrawn due to massive gastrointestinal bleeding requiring a high dose prednisolone. At 6 months, platelet recovery was demonstrated in one patient in the treatment group as well as one in the control group. CONCLUSION: No beneficial effect of H. pylori eradication on platelet recovery in childhood chronic ITP was identified.