Search

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]

Children with transfusion-dependent thalassemia experience stressful conditions related to chronic anemia, repeated blood transfusions, and iron chelation adherence. They are vulnerable to emotional and behavioral problems and psychosocial disturbances. An observational evaluation of psychosocial issues in children with TDTs aged 4–18 using Strengths and Difficulties Questionnaires (SDQ). Psychosocial part in children with TDTs often experiences difficulties in childhood under 10 years old, compared to adolescents (11–18 years) for emotional symptoms and conduct problems. Boys and girls had similar psychosocial problems regarding emotional symptoms, conduct problems, hyperactivity-inatttention, peer relationship problems, and prosocial behavior. In a quarter of cases, they had emotional symptoms, conduct, and hyperactivity-inattention issues, especially in younger children. Interestingly, younger children have more problems than adolescence in peer relations even though they are still under strict parental supervision. Difficulties in emotion, conduct, and hyperactivity would affect their relationship life. Children may try to be accepted by their social environment (prosocial) even though they realize that there are problems in their emotional life and peer relationships. Regular screening of the psychosocial aspects should be followed by counseling because regular transfusion and iron chelation are necessary for long-term management. [ABSTRACT FROM AUTHOR]

Background: Growth retardation is a long-term complication in pediatric transfusiondependent thalassemias (TDTs), presented as short-stature and upper body segment shortening. The cause of this condition was chronic hypoxia, iron overload, endocrinopathy, inadequate transfusion, and iron chelation. We analyze the relationship between ferritin level and growth status of pediatric TDTs. Methods: This was a cross-sectional study on pediatric TDTs aged 2-18 years old at Dr. Soetomo General Academic Hospital Surabaya, Indonesia conducted in 2020. They required blood transfusion every 2-4 weeks. We evaluated the ratio of upper/lower body segments, weight for age Z-score (WAZ), height for age Z-score (HAZ), and body mass index (BMI) Z-score, based on CDC growth chart as growth status parameters. Serum ferritin was checked every three months to determine iron overload and iron chelation (deferiprone, deferasirox and deferoxamine). We used Spearman correlation and Mann-Whitney U test to analyze between variables (a=0.05). Results: We enrolled 15/29 males with median age 10.5 years. Serum Ferritin had negative correlation with the ratio of upper/lower body segments (rho=-0.552; P=0.002), but not for HAZ (rho=-0.078; P=0.694), WAZ (rho=-0.186; P=0.342), BMI Z-score (rho=-0.089; P=0.653) especially if serum ferritin was above 2500 µ/L. In deferiprone group (n=8), the WAZ (P=0.034) and BMI Z-score (P=0.031) were lower; but the ratio of upper/lower body segments was greater (P=0.039) than the deferasirox group. Conclusion: Growth retardation was more visible in pediatric TDTs with high ferritin and in deferiprone group. The height and the ratio of upper/lower body segments of the body were more affected. [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]

The aim of this study was to analyze the diagnostic value of mid regional proadrenomedullin as a sepsis biomarker in pediatric patients with cancer-related chemotherapy. This cross-sectional observational study was located in General Hospital Dr. Soetomo Surabaya from September until December 2020. International Pediatric Sepsis Consensus Conference criteria was used to define sepsis term on 2 study groups. Serum mid regional proadrenomedullin has been drawn from 60 subjects (41 in-ward pediatric patients) and measured on sandwich enzyme-linked immunosorbent assay from Elabscience® Human Mid Regional Proadrenomedullin. Humareader Single Plus® was used to measure the optical density. ROC analysis was used to find out cut off value, sensitivity, specificity, positive predictive value, negative predictive value, negative likelihood ratio, positive likelihood ratio, and accuracy, respectively. Statistics declared significant if p<0.05 (95% CI). Between groups, temperature and heart rate were statistically different (p<0.001; 95% CI). The median difference of mid regional proadrenomedullin between groups was significant (p<0.05; 95% CI). Cut off value 2,88 nmol/L, sensitivity 60.0%, specificity 56.67%, positive predictive value 58.06%, negative predictive value 58.62%, positive likelihood ratio 1.38, negative likelihood ratio 0.71 and diagnostic accuracy 59.33% was obtained while area under curve was 0.707, respectively. Sepsis in children with cancer -related chemotherapy has not well diagnosed by serum mid regional proadrenomedullin. [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]

Copyright of Folia Medica Indonesiana (2355-8393) is the property of Universitas Airlangga and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Overexpression of the antiapoptotic protein Bcl-2 causes apoptosis to stop and conversely the increased expression of the proapoptotic protein Bax makes lymphoblasts easy to destroy. The Bax/Bcl-2 ratio plays a role in the balance of apoptosis, immortality, resistance, and outcome of chemotherapy. We analyzed the relationship between the Bax/BCl-2 ratio and the outcome of induction phase chemotherapy in pediatric Acute Lymphoblastic Leukemia (ALL)., Methods: This research was conducted with a prospective observational study on pediatric ALL aged 1-18 years who were newly diagnosed based on bone marrow aspiration (morphology and immunophenotyping) at Dr. Soetomo General Hospital, Surabaya on October 2020 to March 2021. Expression of Bcl-2, Bax, and Bax/Bcl-2 protein ratio was measured by the flow cytometry method from lymphoblast on bone marrow aspirate samples before and after induction phase chemotherapy according to the 2018 Childhood ALL Indonesian Protocol. The outcomes evaluated were survival and remission rate (lymphoblasts in the bone marrow less than 5%). We used the Mann-Whitney U test and Wilcoxon Signed Rank test to analyze the differences between protein expression with p<0.05 for a two-tailed test., Results: We included 17/26 pediatric ALL, consisting of 88% male, 94% LLA-L1, 76% B cell ALL and 24% T cell ALL. Mean expression of Bax, Bcl-2, and Bax/Bcl-2 protein ratio before chemotherapy among pediatric ALL who alive (N=11) and dead (N=6) were not significantly different (p>0.05). All children who completed the induction phase of chemotherapy went into remission. Bax and Bcl-2 expression before and after chemotherapy showed no difference (p>0.05). The Bax/Bcl-2 ratio increased from 1.74(SD 1.846) to 6.17(4.139) with p=0.021., Conclusion: Expression of Bax, Bcl-2, and Bax/Bcl-2 protein ratio at the beginning of diagnosis did not affect the survival of pediatric ALL after the induction phase of chemotherapy. The Bax/Bcl-2 protein ratio increased 3.5 times in pediatric ALL with remission outcomes, indicating proapoptotic dominance.