RESUMEN
Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long-term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX-induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX-induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM-95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX-induced neurotoxicity were identified using binary logistic regression analysis. Forty-three children were diagnosed with MTX-induced neurotoxicity with an incidence rate of 6.9%. More than two-thirds of them had high-grade MTX-induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase-Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow-up. Univariate analysis found older age (age > 5 years) (p < 0.001), T-cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate-induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re-challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX-induced neurotoxicity during ALL/LBL treatment.
RESUMEN
BACKGROUND AND OBJECTIVES: Improved survival of childhood acute lymphoblastic leukemia (ALL) has diverted attention to the long-term consequences of the treatment; metabolic abnormalities being one of the most important issues. METHODS: Children diagnosed with ALL at age 14 years and younger at Regional Cancer Centre in South India who completed treatment and who were on follow-up for >2 years were enrolled in the study between April 1, 2018 and March 31, 2019. They were prospectively evaluated for the presence of metabolic syndrome (MS) and associated risk factors. RESULTS AND DISCUSSION: A total of 277 survivors of pediatric ALL were recruited during the study period. MS was present in 8.3% (n=23) and 6% (n=13) survivors by National Cholesterol Education Programme Adult Treatment Panel III (NCEPATP III) and International Diabetes Federation (IDF) criteria, respectively. The prevalence of overweight and obesity in the survivors was 9% and 13%. The prevalence of increased waist circumference, low high-density lipoprotein cholesterol, elevated triglycerides, elevated fasting glucose, and increased blood pressure were 10.5%, 28.9%, 24.9%, 2.5%, and 9%, respectively. Overweight/obese survivors were at an increased risk for developing MS (odds ratio=17.66; 95% confidence interval=6.2-50.16, P=0.001). Survivors who received cranial radiotherapy were at an elevated risk for having low high-density lipoprotein cholesterol (P=0.001). CONCLUSIONS: In our study, the prevalence of MS was higher in childhood ALL survivors, as compared with the general population. The study points to the need for regular screening of pediatric ALL survivors for early detection of MS, along with lifestyle modification in those with metabolic abnormalities, to curb the growing incidence of coronary artery disease.
