RESUMEN
BACKGROUND: While Pegaspargase is an essential component of the treatment of acute lymphoid leukemia (ALL) in children, it causes adverse events (AEs) that sometimes make full use impossible. OBJECTIVE: The objective was to investigate the safety of Pegaspargase biosimilar in pediatric ALL patients undergoing treatment according to ICiCLe ALL-14 protocol. METHOD AND MATERIALS: A prospective study was carried out in a university teaching hospital located in the state of Maharashtra, India. Data on clinical factors and adverse reaction characteristics were gathered from hospital medical records. Suspected AEs were classified according to causality and severity. RESULTS: During the study period, 72 children had 52 suspicions of AEs during treatment with biosimilar Pegaspargase. The odds ratio of 1.11 (95%CI, 0.41-2.98) suggested that males and females were both equally likely to experience adverse drug events, despite the fact that the frequency of suspected AEs was higher in boys (66%) than in girls (33%). None of the patients experienced allergic reactions. The high-risk category had the highest number of suspected AEs (56%), followed by intermediate risk (20%) and standard risk (20%). These patients showed a high frequency of suspected AEs during the induction phase (43%) followed by the consolidation phase (26%). Sixty percent of the reactions were classified as grade 1 or 2. ALL cell type (p = 0.02), risk category (p = 0.04) and length of hospitalization (p = 0.003) were significantly correlated with suspected AEs. CONCLUSION: Bio-similar Pegaspargase in combination with chemotherapy was safe and tolerable in the pediatric ALL patients treated according to ICiCLe ALL-14 protocol. Suspected AEs ranged from mild to moderate and hepatic failure and hyperglycemia being severe.
RESUMEN
Methotrexate (MTX) is an extensively prescribed antimetabolite especially in the treatment of several pediatric cancers, though managing toxicities associated with methotrexate in high dose continues to be a challenge. A prospective study was carried out from April 2017 to October 2018. Children of either sex below 18 years at the time of enrolment and receiving high dose Methotrexate intravenous infusion over 24 h as a 2 g/m2, 3 g/m2 and 5 g/m2 dose was included in the study. The serum methotrexate level was estimated after the start of 48 h HDMTX infusion by using the ARCHITECT methotrexate assay. Toxicity due to HDMTX was assessed by Common Terminology Criteria for Adverse Events v.5.0. A total of 244 HDMTX infusions were delivered to 62 ALL patients. From the total of 244 cycles, serum methotrexate level in 35 cycles after the start of 48 h HDMTX infusion was found to be ≥ 1.0 µmol/L with reported toxicities among 31 cycles (88.6%). In 209 cycles MTX level was found to be less than 1.0 is statistically significant as compared to other cycles (p < 0.0001). Highest toxicities reported were in cycle I (38.8%). The toxicities such as oral mucositis, neutropenia, the elevation of liver enzymes, dermatological toxicities were found more in cycles whose methotrexate level are greater than 1.0 µmol/L. Dose reduction, increased the length of stay and treatment delay occurred in patients with severe toxicities. Severe toxicities of methotrexate can be interrelated with serum methotrexate levels at 48 h after the start of HDMTX infusion.