Relationship between serum ferritin and growth status of pediatric transfusion dependent thalassemia.

Background: Growth retardation is a long-term complication in pediatric transfusion-dependent 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 (α=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.

Relationship between Bax and Bcl-2 Protein Expression and Outcome of Induction Phase Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

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.

Hospital acquired pneumonia risk factors in children with Acute Lymphoblastic Leukemia on chemotherapy.

BACKGROUND: Over the past 10 years, infection has remained as the main cause of illness and mortality among children with Acute Lymphoblastic Leukemia on chemotherapy. The high incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy with risk factors should be intervened earlier. METHODS: An observational case control study of children with Acute Lymphoblastic Leukemia on chemotherapy. Patient with Hospital-Acquired Pneumonia considered as case and patient without Hospital-Acquired Pneumonia as control to analyze risk factors that affect the incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy from 2016 to 2018 was performed in the pediatric ward Dr. Soetomo General Academic Hospital with a total sampling technique. Nine risk factors were analyzed: age, gender, nutritional status, length of stay, risk stratification, chemotherapy phase, anemia, neutropenia, and thrombocytopenia. Bivariate and multivariate analysis using chi-square, continuity correction, and logistic regression was used for statistical analysis. RESULTS: 120 children enrolled the study. Analyzed of risk factors showed risk stratification (p = 0.009), chemotherapy phase (p < 0.001), and neutropenia (p < 0.001) was proven to significantly affect the incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy. Age, gender, nutritional status, length of stay, anemia, and thrombocytopenia were not proven to be a risk factor that affects the incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy. CONCLUSION: The incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy is significantly affected by the risk stratification, chemotherapy phase, and neutropenia.

Risk Factors of Daunorubicine Induced Early Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia: A Retrospective Study.

BACKGROUND: Daunorubicine, a type of anthracycline, is a drug commonly used in cancer chemotherapy that increases survival rate but consequently compromises with cardiovascular outcomes in some patients. Thus, preventing the early progression of cardiotoxicity is important to improve the treatment outcome in childhood acute lymhoblastic leukemia (ALL). OBJECTIVE: The present study aimed to identify the risk factors in anthracycline-induced early cardiotoxicity in childhood ALL. METHODS: This retrospective study was conducted by observing ALL-diagnosed children from 2014 to 2019 in Dr. Soetomo General Hospital. There were 49 patients who met the inclusion criteria and were treated with chemotherapy using Indonesian Childhood ALL Protocol 2013. Echocardiography was performed by pediatric cardiologists to compare before and at any given time after anthracycline therapy. Early cardiotoxicity was defined as a decline of left ventricle ejection fraction (LVEF) greater than 10% with a final LVEF < 53% during the first year of anthracycline administration.  Risk factors such as sex, age, risk stratification group, and cumulative dose were identified by using multiple logistic regression. Diagnostic performance of cumulative anthracycline dose was evaluated by receiver operating characteristic (ROC) curve. RESULTS: Early anthracycline-induced cardiotoxicity was observed in 5 out of 49 patients. The median cumulative dose of anthracycline was 143.69±72.68 mg/m2. Thirty-three patients experienced a decreasing LVEF. The factors associated with early cardiomyopathy were age of ≥ 4 years (PR= 1.128; 95% CI: 1.015-1.254; p= 0.001), high risk group (PR= 1.135; 95% CI: 1.016-1.269; p= 0.001), and cumulative dose of ≥120 mg / m2 (CI= 1.161; 95% CI:1.019-1.332). CONCLUSION: Age of ≥ 4 years, risk group, and cumulative dose of ≥120 mg/m2 are significant risk factors for early cardiomyopathy in childhood ALL.