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Background: 6-Mercaptopurine (6-MP) is considered the backbone of therapy in the maintenance phase of acute lymphoblastic leukemia (ALL). Gene polymorphisms involved in thiopurine degradation are predictors of toxicity in patients treated with 6-MP. We investigated the effects of nucleoside diphosphate linked moiety X (nudix) type motif 15 (NUDT15) polymorphism NUDT15c.415C>T on neutropenia incidence, dose adjustment for 6-MP, and survival rates in Thai children with ALL. Methods: Children diagnosed with ALL who received 6-MP in the maintenance phase of treatment, in 2005-2016, were retrospectively enrolled. Results: The subjects consisted of 102 patients (median age, 5.2 years; 58 boys). On genetic testing 78, 22, and two patients were normal (CC), heterozygous (CT), and homozygous (TT), respectively. The incidence of neutropenia at 3 months was significantly higher in the CT/TT than CC polymorphism groups (OR, 12; 95%CI: 3.781-38.085, P < 0.001). The mean dose of 6-MP at 3, 6, and 12 months was significantly lower in the CT/TT versus the CC group (P < 0.001). The 5 year overall survival (OS) rate for CC was 80.4%, and for CT/TT, 95.5% (P = 0.34). The 5 year event-free survival (EFS) for CC and CT/TT was 75.1% and 85.7%, respectively (P = 0.17). After adjusted risk classification, no significant differences were observed for OS or EFS between the CC and CT/TT groups. Conclusion: Patients harboring the CT/TT polymorphism of NUDT15 had a significantly higher incidence of neutropenia during the first 3 months of maintenance, resulting in significantly lower doses of 6-MP.

IntroductionThe number of pediatric COVID-19 infections is increasing; however, the data on long COVID conditions in children is still limited. Our study aimed to find the prevalence of long COVID in children during the Delta and Omicron waves, as well as associated factors.MethodsA single-center prospective cohort study was conducted. We included 802 RT-PCR-confirmed COVID-19 pediatric patients in the Delta and Omicron periods. Long COVID was defined as having symptoms for ≥3 months after infection. Parents and/or patients were interviewed by phone. Multivariable logistic regression was performed to find associated factors with long COVID.ResultsThe overall prevalence of long COVID was 30.2%. The Delta period had more prevalence than the Omicron (36.3% vs. 23.9%). Common symptoms for patients 0–3 years’ old were loss of appetite, rhinorrhea, and nasal congestion. Conversely, patients 3–18 years’ old had hair loss, dyspnea on exertion, rhinorrhea, and nasal congestion. However, there was no significant negative impact on daily life. Most symptoms improved after a 6-month follow-up. Factors associated with long COVID-19 conditions were infection during the Omicron period (adjusted OR: 0.54; 95% CI: 0.39–0.74, P &lt; 0.001), fever (adjusted OR: 1.49, 95% CI: 1.01–2.20, P = 0.04) and rhinorrhea (adjusted OR: 1.47, 95% CI: 1.06–2.02, P = 0.02).ConclusionInfection during the Omicron wave has a lower prevalence of long COVID. The prognosis is often favorable, and most symptoms gradually become less. However, pediatricians may schedule appointments to surveil long COVID in children with fever or rhinorrhea as an initial symptom.

Mediastinal germ cell tumor (MGCT), which accounts for 1% to 3% of extragonadal germ cell tumors, has unique manifestations; it is associated with several types of hematologic malignancy, particularly myeloid neoplasm. The aim of this study was to report the 10-year incidence, clinical characteristics, and outcomes of MGCT at Thailand's national pediatric tertiary referral center. This retrospective study included patients diagnosed with MGCT at the Department of Pediatrics, Siriraj Hospital during 2005 to 2014. Eight patients (all male) were diagnosed with MGCT. Five of 8 patients were found to have hematologic abnormalities. Three patients were diagnosed with acute myeloid leukemia (AML) (one patient with M1, another having M7, and the other with M0). Another patient had mixed MGCT with mediastinal myeloid sarcoma (MMS). The other patient had malignancy-associated hemophagocytic lymphohistiocytosis syndrome (M-HLH). Isochromosome 12p was detected in 3 patients (AML [2], mixed MGCT/MMS [1]). Four of 5 patients with hematologic abnormalities died of hematologic abnormalities or treatment complication (AML [3], M-HLH [1]). One patient with mixed MGCT/MMS survived with chemotherapy. All patients with AML and MMS were nonseminomatous MGCT and the onset of myeloid malignancies were within 1 year after the diagnosis of MGCT. Associated hematologic malignancies should be suspected in MGCT with abnormal blood count or hematologic symptoms. Isochromosome 12p was the most common cytogenetic finding in MGCT-associated myeloid malignancies patients. Those with nonseminomatous MGCT should have their blood count carefully monitored especially during the first year after the diagnosis of MGCT. Better treatment alternatives for MGCT with associated hematologic malignancies are warranted to ameliorate adverse outcomes.

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