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Background: Methotrexate-induced toxicities often occur in pediatric ALL undergoing chemotherapy. Methotrexate is inhibiting folate metabolism so no DNA synthesis occurs. Folate deficiency can occur before and after administration of methotrexate high dose (MTX-HD). This also may affect the outcome of chemotherapy. However, there has been limited research on folate levels in blood during MTX-HD therapy and its correlation to toxicity. Objective: To analyze the correlation between folate levels and toxicity following high-dose methotrexate (MTX-HD) administration in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: This prospective observational study included 31 pediatric ALL patients aged 1-18 years undergoing consolidation phase chemotherapy. Serum folate levels were measured before and after MTX-HD using CalSet Folate, and MTX-induced toxicities were observed within 48 hours postadministration. Data were analyzed using the Wilcoxon Signed Rank test and Spearman Correlation Test, with p<0.05 considered significant. Results: Thirty-one subjects were included, with a median age of 4 years. Median folate levels increased significantly from 23.5 ng/mL before to 40 ng/mL after MTX-HD (p<0.05). Common toxicities included mucositis (100%), neutropenia (45.2%), DILI (35.5%), and AKI (6.4%). No significant correlation was found between folate levels and these toxicities (p>0.05). Conclusion: Significant differences in folate levels were observed before and after MTX-HD. Despite high folate levels, MTX-induced toxicities still occurred, suggesting other factors may contribute to toxicity. [ABSTRACT FROM AUTHOR]

Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Emergency complications such as hyperleukocytosis can arise as the disease develops. Exchange transfusion is one of many cytoreductive modalities to resolve the condition. Objective To analyze the clinical and laboratory effects of exchange transfusion in childhood acute lymphoblastic leukemia patients with hyperleukocytosis. Methods This analytical retrospective cohort study with a preand post-test design used secondary medical record data. The obtained characteristics were the incidences of dyspnea, tachypnea, headache, intracranial bleeding, hepatomegaly, splenomegaly, lymphadenopathy, abdominal pain, fever, pallor, nausea/vomiting, and skin or mucosal bleeding; hemoglobin, white blood cell, and platelet counts; and serum potassium, sodium, calcium, phosphate, blood urea nitrogen, and creatinine levels. Results A total of 16 patients underwent exchange transfusion; they had significant reductions of the incidence of dyspnea, tachypnea, hepatomegaly, and pallor and significant improvement in the form of elevation of hemoglobin level and decrease in white blood cell counts (P<0.05 for all) compared to pre-treatment. The remainder of the variables were not significantly different between pre- and post-treatment, but a general decrease in all clinical manifestations except intracranial bleeding was observed. Conclusion Exchange transfusion has the beneficial effect of resolving hyperleukocytosis and its manifestations, although correction in laboratory outcomes that remained abnormal are still needed. [ABSTRACT FROM AUTHOR]

Introduction: Caspase-3 is a crucial mediator of the extrinsic apoptosis pathway. The role of caspase-3 for extrinsic apoptosis signalling is still a challenge and should be exploited in childhood ALL. This study aimed to compare the caspase-3 expression in the patient's bone marrow before and after the induction phase of chemotherapy in childhood ALL. It will also to correlate the mean difference in caspase-3 expression between ALL standard-risk and ALL high-risk patients. Methods: Seventeen newly diagnosed ALL subjects were enrolled in this study. Caspase-3 expression in bone marrow was assessed using flow cytometry and monoclonal antibodies. A T-test and a paired T-test were used to compare between groups. The correlation coefficient between ALL groups was evaluated using Spearman's test and linear regression with a significant p-value of 0.05. Results: The caspase-3 expression is higher after induction therapy. However, it showed an insignificant difference (16.56+12.91% vs 27.71+12.33%; p = 0.08, p > 0.05). The mean difference of caspase-3 in ALL high-risk groups was significantly higher than in ALL standard-risk groups with a positive correlation (p = 0.007, r = 0.756). Conclusion: The caspase-3 expression after induction phase chemotherapy was increased in all standard-risk and high-risk patients; other lymphoblast apoptosis markers need to be confirmed alongside caspase-3. [ABSTRACT FROM AUTHOR]

Introduction: L-asparaginase chemotherapy often causes hepatotoxicity and affects complete remission in pediatric acute lymphoblastic leukemia (ALL). This study aims to investigate the risk factors that affect the incidence of hepatotoxicity caused by L-asparaginase chemotherapy in ALL children. Methods: An observational study with prospective sampling was conducted at Dr. Soetomo Hospital, Surabaya. The inclusion criteria included ALL children aged 1-18 years, undergoing ALL Induction phase chemotherapy based on the 2018 Indonesian Children's ALL protocol as evidenced by bone marrow aspiration, receiving L-asparaginase chemotherapy, and obtaining written consent from parents or guardians. Each child had 3 ml of blood drawn from a peripheral vein to assess their complete blood count, alanine transaminase (ALT) levels, and albumin level. Results: Thirty-two children with ALL were collected. Two of them were excluded due to allergic reaction and enable to continue the L-asparaginase chemotherapy. Thirty of them were eligible participants. Approximately 53.3% of ALL children aged ≤ seven years. Fourteen (47%) children with ALL were included in the standard-risk group and 16 (53%) of them included high-risk group. There were significant differences in ALT levels between the four stages of observation (p=<0.001). Twenty-two ALL children had hepatotoxicity (73.3%), while 8 had non-hepatotoxicity (26.7%). Two risk factors had a significant influence on the occurrence of hepatotoxicity due to L-asparaginase chemotherapy including age and hypoalbuminemia (p=0.045, p=0.028). Conclusion: Age and hypoalbuminemia were the risk factors that might affect the incidents of hepatotoxicity. Clinical monitoring before and after treatment needs to be done to prevent poor outcomes. [ABSTRACT FROM AUTHOR]

Background: Mortality due to Infection associated therapy in acute lymphoblastic leukemia (ALL) children remains high, although therapeutic success and survival rate are substantially improving. Methods: This study used a pre and post-test group design for children aged less than 18 years with ALL newly diagnosed and receiving chemotherapy in pediatric patient of Dr. Soetomo hospital Surabaya. Results: The study involved 25 subjects, 10 subjects were male, average age ranged from 3 to 9 years. The high risk-ALL subjects were 15 (60%), hyperleukocytosis 4 (16%) subjects and 7 (28%) subjects with leukopenia. Statistical analysis showed a significant difference in decreasing cortisol levels in week-4 compared to week-0 (p <0.001) and an increased in cortisol levels between week-12 compared to week-10. The incidence of infection during induction phase is higher than the consolidation phase (40vs15). The relationship between the mean cortisol levels and the incidence of infection in general showed a significant difference in the induction phase of week-0 (p=0.029), week-4 (p=0.041), and week-6 (p=0.005). Conclusion: In the induction phase, there is an association between mean cortisol levels and the risk of infection, but there is no such association in the consolidation phase. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia is a recognized side effect of the corticosteroids and asparaginase given during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). The ALL is the malignant tumor with the highest incidence in the childhood. The aim of this study is to investigate the impact of hyperglycemia during induction chemoteraphy in childhood ALL. Methods: This prospective study was done in Dr. Soetomo hospital from January to April 2018. The subject was newly diagnosed as ALL under the age of 18 years, treated with Indonesian childhood ALL 2013 protocol (Standard Risk (SR) group and High Risk (HR) group). Hyperglycemia was defined as at least two separate random plasma glucose levels > 200 mg/dL, which was evaluated before and during induction chemotherapy. Statistical analysis using Paired T-test for parametric and Wilcoxon Test for nonparametric. Results: Thirty-three children were enrolled, 18/33 boys with mean age 5.8 (SD 3.78) years, compromised as ALL-L1 30/33. They were treated with ALL-HR 19/33 and ALL-SR 14/33. In overall groups, the mean random blood glucose level significantly increased from 108 (SD 21.3) mg/dL to 147 (SD 48.1) mg/dL, (mean difference 38.67 mg/dL; 95% CI 18.08 to 59.26 mg/dL, P=0.008). In SR group, there was a significant increased of mean random blood glucose level from 102 (SD 13.5) mg/dL to 133 (SD 37.3) mg/dL, (mean difference 31.8 mg/dL; 95% CI 8.78 to 54.8 mg/dL; P=0.01). In HR group, the mean random blood glucose level increased from 113 (SD 51.9) mg/dL to 165 (SD 25.4) mg/dL, (mean difference 51.9 mg/dL; 95% CI 18.6 to 85.2 mg/dL, P=0.004). Conclusion: Blood glucose level is significantly increase during induction chemotherapy in both SR and HR Indonesian childhood ALL 2013 protocol. [ABSTRACT FROM AUTHOR]