Discussion:
The intracellular aspartic acid is removed by L-asparaginase through hydrolysis, and tumor cells cannot synthesize aspartic acid, thus preventing protein synthesis and inducing apoptosis. Asparaginase is a crucial drug used in chemotherapy for ALL. It may have many side effects, among which pancreatitis is one of the most serious one. Pancreatitis may affect the tolerance of chemotherapy and the prognosis of ALL. Understanding the risk factors and predicting the occurrence of acute pancreatitis is essential for improving clinical management.
The risk factors for pancreatitis in children with ALL undergoing chemotherapy remain unclear. Some reports suggest that the dosage of asparaginase is an independent risk factor. [12] However, no significant association has been reported between asparaginase use and the development of pancreatitis.[13] The incidence of pancreatitis in our study did not differ significantly between genders, consistent with prior findings.[14, 15] The results of univariate analysis in this study suggest that the pancreatitis group used less asparaginase than the control group, which may be related to discontinuing asparaginase application after pancreatitis. In the pancreatitis group, the proportion of abnormal pancreatic morphology was higher, but the results of multivariate analysis showed that it was not an independent risk factor.
This study developed a model to predict acute pancreatitis risk in ALL patients undergoing chemotherapy, using baseline and pre-treatment data. Independent risk factors included increased total bilirubin, direct bilirubin, and induction phase. These data are easy to obtain before chemotherapy, increasing the feasibility of its clinical application, and all patients are uniformly treated with CCLG-ALL regimen, which can reduce confounding interference. The model also proved to have good predictive power in external validation. Consistent with prior research, the high rate of pancreatitis observed during induction therapy, often following the first few doses of asparaginase, suggests a potential predisposing factor or genetic susceptibility for pancreatitis.[16] The elevated level of bilirubin may be related to hepatopancreatic ampullary edema and bile excretion disorder, suggesting that pancreatitis after asparaginase administration may be related to obstruction of biliary tract.[17] Oxidative stress is implicated in pancreatitis, and given bilirubin’s antioxidant capacity, low total bilirubin levels could be associated with severe pancreatitis.[18] Further studies may be required to determine the relationship between the severity of post-chemotherapy pancreatitis and bilirubin levels and whether pancreatitis is associated with obstruction of biliary tract.
Patients with definite diagnosis of acute pancreatitis were included in this study. During data collection, some patients exhibited mild pancreatic abnormalities and slightly elevated pancreatic enzyme levels before starting chemotherapy. These patients did not develop pancreatitis after chemotherapy, but also may affect the clinician’s decision to use asparaginase, so it is necessary to evaluate the risk of pancreatitis of these patients in the future. Genetic factors, including variations in genes like PRSS1, PRSS2, SPINK1, CFTR, CTRC, CASR, CLDN2, CPA1, and HLA-DRB1*07:01, have been associated with an increased risk of pancreatitis. Future studies should include relevant genes as possible risk factors to assess their impact on the development of pancreatitis.[19-21] The small sample size, a consequence of the low incidence of pancreatitis, limits the generalizability of the study’s findings. Larger studies are needed to validate these results.
Asparaginase is an essential component of chemotherapy treatment for patients with acute lymphoblastic leukemia. However, the occurrence of pancreatitis will affect the application of this drug, affecting the overall chemotherapy tolerance and disease prognosis. The construction of prediction model related to pancreatitis is beneficial to avoid treatment-related pancreatitis, improve treatment tolerance, and improve disease prognosis. Studies should also be conducted to compare the side effects and long-term outcomes of reuse versus discontinuation of asparaginase so that clinicians can weigh the pros and cons.[22]
Reference:
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