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]
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