Asparaginase-associated pancreatitis in chemotherapy-treated pediatric patients: a five-year retrospective study.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu CX
PROVIDER: S-EPMC9233968 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Asparaginase-associated pancreatitis in chemotherapy-treated pediatric patients: a five-year retrospective study.
Liu Chen-Xi CX Zhang Yun-Yu YY Yang Qiu-Shi QS Shen Shu-Hong SH Chen Jing J Tang Yan-Jing YJ Chen Chang-Cheng CC Wang Zhuo Z Li Bi-Ru BR Qian Juan J Wang Ying Y Hu Wen-Ting WT Ning Bo-Tao BT
World journal of emergency medicine 20220101 4
Similar Datasets
Project description:IntroductionTuberculosis remains a major public health problem, primarily in low- and middle-income countries. Evaluating treatment outcomes and investigating factors associated with them are essential for the treatment and control of tuberculosis. Hence, this study aims to assess the TB treatment outcomes and associated factors in Bosaso, Puntland, Somalia.MethodsA 5-year facility-based retrospective study was conducted at Bosaso TB Hospital, from January 2018 to December 2022. A total of 2213 TB patients were included in this study. Demographic, clinical characteristics and treatment outcome data were gathered from the TB register using a structured checklist. Data were entered, cleaned, and analyzed using SPSS version 20. Descriptive statistics and binary logistic regression analysis were employed. A P-value of less than 0.05 was considered statistically significant.ResultsThe overall successful treatment rate was 88.5%. The TB treatment success rate over the last three years was comparable to the global target of the End TB strategy of ≥ 90% by 2025. Patients aged 21-40 years (AOR = 0.59, 95% Cl = 0.41-0.84, p = 0.004), 41-60 years (AOR = 0.37, 95% CI = 0.25-0.55, p < 0.001), and ≥ 61 years (AOR = 0.37, 95% CI = 0.22-0.64, p < 0.001) were less likely to achieve successful treatment outcomes. Being HIV-positive (AOR = 0.41, 95% Cl = 0.21-0.79, p = 0.008) was less likely to be associated with a successful treatment outcome.ConclusionIn this study, the TB treatment success rate over the last three years was comparable to the global target of the End-TB strategy of ≥ 90% by 2025. Therefore, we recommend strengthening the TB care system, conducting regular supportive supervision for TB facilities, implementing strategies to encourage drug adherence, strengthening mechanisms to minimize the anti-TB treatment default rate, improving counseling services, and giving more attention to the vulnerable age groups and HIV-positive patients.
| S-EPMC11761147 | biostudies-literature
Project description:ObjectiveExtranodal natural killer/T cell lymphoma (NKTCL) is an aggressive EBV-related lymphoma, originating from NK cells or T cells. Previous study demonstrated that CD56 negative NKTCL should be recognized as a distinct subtype. In this study, the value of CD56 in NKTCL is validated in the era of asparaginase, and genomic analysis was done to dissect the differences between CD56-negative and positive NKTCL.Methods443 patients with newly diagnosed NKTCL were enrolled in this retrospective study, and correlation between CD56 positivity and survival outcomes was analyzed. The gene sequencing data was downloaded (http://www.biosino.org/node/project/detail/OEP000498), and bioinformatics analysis was done to delineate the tumor microenvironment and differentially expressed genes.ResultsCD56 was expressed in 337 patients (76.1%). Within a median follow-up time of 51 months, the 5-year overall survival (OS) and progression free survival (PFS) rates were 63.8% and 51.9%, respectively. For the whole cohort, patients who were CD56-positive had superior OS (5-year OS, 86.2% vs. 51.9%, p=0.019) and PFS (5-year PFS, 55.9% vs. 40.1%, p=0.016). For patients in early stage disease, CD56 positivity was associated with superior OS and PFS (p=0.008 and 0.005, respectively). In patients who received non-asparaginase-based chemotherapy, CD56-negative was associated with shorter OS and PFS (p<0.001), and in patients who received asparaginase-based chemotherapy, CD56-negative was not related to inferior OS and PFS (p=0.093 and p=0.829, respectively). The genomic analysis demonstrated that CD56 positive NKTCL probably originated from NK cells and CD56 negative NKTCL originated from T cells. CD56 positive NKTCL had significantly higher proportion of resting NK cells, activated NK cells, and activated CD8+ and CD4+ T cells in the tumor microenvironment.ConclusionsCD56 negative NKTCL differs from CD56 positive NKTCL in both the tumor microenvironment and survival outcomes, and asparaginase-based treatment may overcome the poor prognosis brought by CD56 negativity.
| S-EPMC8968031 | biostudies-literature
Project description:The purpose of the study was to analyze the clinical characteristics and the course of diagnosis and therapy of asparaginase-associated pancreatitis (AAP) in childhood, improve the ability of diagnosis and treatment, and evaluate ULK2 gene polymorphism as a predictive factor for AAP. Data of 12 patients with childhood AAP were reviewed. Sanger sequencing of ULK2 gene was performed in AAP group (n=12) and control group (n=146). The main symptoms of AAP were abdominal pain and vomiting. Generally, the levels of amylase and lipase in the serum peaked within 72 h. Abdominal ultrasonography was performed in 11 patients; seven patients exhibited findings of pancreatic enlargement. Computed tomography was performed in 9 patients. Five patients exhibited findings of pancreatic enlargement and peri-pancreatic exudation. All patients were managed by fasting at the early stage, and seven patients underwent placement of a nasojejunal tube to receive enteral nutrition. One patient underwent endoscopic retrograde cholangiopancreatography (revealing dilation of the pancreatic duct) and endoscopic retrograde pancreatic drainage. Another patient developed signs of shock and received continuous renal replacement. There were no deaths caused by AAP. Therefore, early identification of patients at risk of AAP is of great importance. In addition, repeated elevation in the levels of pancreatic enzymes is indicative of complications. Sanger sequencing analysis of ULK2 gene showed that there was a significant difference of EXON1: -493C>T and EXON1: -308C>G between the AAP group and control group (P<0.0001). Thus, ULK2 gene polymorphism may be associated with the development of AAP. However, more validation of this finding is needed.
| S-EPMC7137003 | biostudies-literature
Project description:IntroductionTo assess the frequency of allergic reactions to asparaginase (ASP) and possible risk factors for reactions in a cohort of pediatric patients.MethodThe study was performed based on retrospective data from patients under acute lymphoid leukemia treatment in a general university hospital located in southern Brazil. Information on patients who used ASP from 2010 to 2017 was collected. Allergic reactions were identified in electronic medical records.ResultsAmong the 98 patients included in the study, 16 (16.3 %) experienced an allergic reaction to native l-asparaginase (L-ASP). Of the 22 patients (22.4 %) that received only intravenous (IV) administration of l-ASP, 10 (62.5 %) had allergic reactions, while 48 patients (49 %) received intramuscular (IM) administration and 28 (28.6 %) received IV and IM administrations. The occurrence of allergic reactions differed between the groups (p < 0.001), and IV administration was associated with allergic reactions. Association was also observed between the severity of the reaction and the route of administration, with the IM route associated with grade 2 and IV route associated with grade 3. Occurrence of allergic reactions was higher when the commercial formulation of l-ASP, Leuginase®, was used (p = 0.0009 in the analysis per patient and p = 0.0003 in the analysis per administration).ConclusionsThe IV administration and commercial Leuginase® presentation were associated with more allergic reactions in the study population, which corroborates the findings in the literature. The IV route was also associated with higher severity of reactions in the present study.
| S-EPMC7910154 | biostudies-literature
Project description:AimsL-asparaginase is an essential medicine in the treatment of pediatric acute lymphoblastic leukemia (ALL) and the quality of generic formulations is an area of concern. We compared nine generic formulations of L-asparaginase available in India with the innovator.MethodsThe quality of formulations was assessed by measuring 72-hour trough asparaginase activity in children with ALL during induction following administration of 10,000 IU/m2 of L-asparaginase. In-vitro analysis of the label claim was assessed by measuring activity of three generic formulations. Liquid chromatography-mass spectrometry (LC/MS) was used to determine the amount of host contaminant proteins (HCPs) in the formulations.ResultsBetween March 2015 to June 2018, 240 samples from 195 patients were analyzed. The number of samples analyzed ranged from 7-66 per generic brand (median: 18) and seven of the innovator. The proportion of generic formulations that failed to achieve a predefined clinical threshold activity of 50 IU/L ranged from 16.7% (2/12) to 84.9% (28/33) in the highest activity to lowest activity generic respectively. On other hand, all innovator samples had activity greater than 50 IU/L. In-vitro asparaginase activity in the three generic formulations tested ranged from 71.4-74.6% of the label claim (10,000 IU) compared to 93.5% for the innovator. LC/MS analysis of generic 5 identified 25 HCPs with a relative peptide count of 27.1% of the total peptides.ConclusionsGeneric formulations had lower asparaginase activity which raises serious clinical concerns regarding their quality. Until stringent regulatory enforcement improves the quality of these generics, dose adaptive strategies coupled with therapeutic drug monitoring need to be considered.
| S-EPMC7256116 | biostudies-literature
Project description:Asparaginase-associated pancreatitis (AAP) frequently affects children treated for acute lymphoblastic leukemia (ALL) causing severe acute and persisting complications. Known risk factors such as asparaginase dosing, older age and single nucleotide polymorphisms (SNPs) have insufficient odds ratios to allow personalized asparaginase therapy. In this study, we explored machine learning strategies for prediction of individual AAP risk. We integrated information on age, sex, and SNPs based on Illumina Omni2.5exome-8 arrays of patients with childhood ALL (N=1564, 244 with AAP 1.0 to 17.9 yo) from 10 international ALL consortia into machine learning models including regression, random forest, AdaBoost and artificial neural networks. A model with only age and sex had area under the receiver operating characteristic curve (ROC-AUC) of 0.62. Inclusion of 6 pancreatitis candidate gene SNPs or 4 validated pancreatitis SNPs boosted ROC-AUC somewhat (0.67) while 30 SNPs, identified through our AAP genome-wide association study cohort, boosted performance (0.80). Most predictive features included rs10273639 (PRSS1-PRSS2), rs10436957 (CTRC), rs13228878 (PRSS1/PRSS2), rs1505495 (GALNTL6), rs4655107 (EPHB2) and age (1 to 7 y). Second AAP following asparaginase re-exposure was predicted with ROC-AUC: 0.65. The machine learning models assist individual-level risk assessment of AAP for future prevention trials, and may legitimize asparaginase re-exposure when AAP risk is predicted to be low.
| S-EPMC8946594 | biostudies-literature
Project description:Asparaginase, an agent used in the treatment of acute lymphoblastic leukemia (ALL), is associated with the development of pancreatitis. The clinical course and long-term outcome of patients experiencing this complication has not been extensively detailed.We reviewed the clinical course for all children with ALL diagnosed with pancreatitis at the Dana-Farber Cancer Institute/Children's Hospital Boston between 1987 and 2003. The outcome of these patients was compared with that of patients with ALL who did not experience pancreatitis.Twenty-eight of 403 children (7%) were diagnosed with pancreatitis. Patients 10-18 years old at diagnosis had 2.4 times the risk of developing pancreatitis compared with younger patients. Pancreatitis typically occurred early in the course of therapy (median 4 weeks after first dose of asparaginase). Ninety-three percent of affected patients were hospitalized and 57% received parenteral nutrition. No patient developed chronic sequelae or died as a result of pancreatitis. Sixteen (57%) patients were re-treated with asparaginase, 10 of whom had another episode of pancreatitis. No significant differences in event-free survival were observed when comparing patients with and without a history of pancreatitis.Asparaginase-associated pancreatitis was more common in older children, and caused significant acute morbidity. It tended to occur after the first few doses of asparaginase, suggesting a predisposition to this complication rather than a cumulative drug effect. Re-treatment with asparaginase after an episode of pancreatitis was associated with a high risk of recurrent pancreatitis.
| S-EPMC2721691 | biostudies-literature
Project description:Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.
| S-EPMC10205044 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC.MethodA total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured.ResultsThe non-survival group had increased levels of white blood cells, neutrophils (both p<0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05].ConclusionThis study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools.
| S-EPMC11456424 | biostudies-literature
Project description:Fever in neutropenia (FN) is the most frequent potentially lethal complication of chemotherapy in patients with cancer. The temperature limit defining fever (TLDF) for FN is based on scarce evidence. This prospective, single center observational study recruited non-selected pediatric patients diagnosed with cancer between ≥1 and ≤17 years in 2012 and 2013. Of 40 patients potentially eligible, 39 participated. Data of 8896 temperature measurements and 1873 complete blood counts (CBCs) were recorded over 289 months (24.1 years) of chemotherapy exposure time. During this time 43 FN episodes were diagnosed. In 32 episodes, FN diagnosis was based on reaching the local (i.e. Bern, Switzerland) standard TLDF of 39.0 °C; another 11 episodes had been captured by clinical judgement (i.e. temperature < 39.0 °C). These data can be used to simulate the effects of various TLDFs on the rate of FN diagnosis. We assume merging these data with other data sets is feasible.
| S-EPMC6610087 | biostudies-literature