Predictors of hepatotoxicity and pancreatitis in children and adolescents with acute lymphoblastic leukemia treated according to contemporary regimens

Denton, Christopher; Rawlins, Yasmin; Oberley, Matthew J.; Bhojwani, Deepa; Orgel, Etan

doi:10.1002/pbc.26891

Cited by 58 publications

(77 citation statements)

References 58 publications

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“…The cumulative risk of pancreatitis in our cohort was similar to that found in previously published results in asparaginase intensive protocols . Our failure to reproduce the association between BMI and risk of pancreatitis could be attributable to type 2 error due to a limited number of patients in the overweight and obese groups, though the total cohort was four times larger than the cohort used by Denton et al …”

Section: Baseline Characteristics and Cumulative Incidences Of Pancresupporting

confidence: 77%

“…Using comprehensible inclusion criteria with prospective registration of pancreatitis in a large well‐described cohort, all following the same treatment protocol, we were unable to reproduce the association between obesity and risk of pancreatitis but were able to produce the well‐known, increased risk of pancreatitis for adolescents with ALL . The cumulative risk of pancreatitis in our cohort was similar to that found in previously published results in asparaginase intensive protocols .…”

Section: Baseline Characteristics and Cumulative Incidences Of Pancresupporting

confidence: 51%

“…Recently, Denton et al. published in this journal that obesity in children with ALL was associated with risk of pancreatitis . Since obesity is an increasing global health issue, hypertriglyceridemia is a risk factor for pancreatitis in non‐ALL adults, and obesity and triglyceride levels are correlated, an association seems plausible, although a recent study failed to demonstrate hypertriglyceridemia as a risk for pancreatitis in children with ALL .…”

Section: Baseline Characteristics and Cumulative Incidences Of Pancrementioning

confidence: 99%

See 2 more Smart Citations

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Mogensen

Wolthers

Grell

et al. 2018

Pediatric Blood & Cancer

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Section: Baseline Characteristics and Cumulative Incidences Of Pancresupporting

confidence: 77%

Section: Baseline Characteristics and Cumulative Incidences Of Pancresupporting

confidence: 51%

Section: Baseline Characteristics and Cumulative Incidences Of Pancrementioning

confidence: 99%

See 1 more Smart Citation

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Mogensen

Wolthers

Grell

et al. 2018

Pediatric Blood & Cancer

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“…Hepatotoxicity is a common treatment-related toxicity (TRT) during contemporary treatment regimens for ALL. Denton et al (10) identified 262 patients, of whom 71 (27%) developed hepatotoxicity. Approximately 25% of hepatotoxicities (18/71) occurred during induction alone.…”

Section: Discussionmentioning

confidence: 99%

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia

Zawitkowska

Lejman

Zaucha‐Prażmo

et al. 2019

In Vivo

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Background/Aim: The risk factors, clinical features and non-hematological toxicity profiles during chemotherapy in acute lymphoblastic leukemia (ALL) patients treated in pediatric hematology centres were analysed. Materials and Methods: A total of 902/1872 children were reported as having grade 3 or 4 toxicity. Results: Among the analysed toxicities, infection and gastrointestinal and liver toxicities were the most common. The median follow-up was 6.8 years. Overall survival and event-free survival rates for the analysed group were lower than those reported for the group without grade ≥3 toxicity. In univariate analysis, we identified the number of toxic episodes, the risk group and remission status that had a significant impact on the outcome. Multivariate analysis demonstrated the risk group and the number of toxic episodes ≥3 to be statistically significant for the results. Conclusion: The toxic profiles investigated in our report should be used in future efforts to decrease the burden of side effects during chemotherapy. Over the last years, there has been an improvement in the overall survival of childhood acute lymphoblastic leukemia (ALL), which is now around 80-90%. This is due to contemporary multidrug therapy regimens but, on the other hand, patients are burdened with severe complications of treatment (1, 2). Chemotherapy has a range of side-effects, such as infection, organ damage, hematological and other (malnutrition, hair loss). Most agents causing immunosuppression and myelosuppression increase the risk of bacterial, viral and fungal infections. The infection is still a major cause of death in ALL children (3, 4). Every organ may be adversely affected by anti-leukemic treatment, the most 1333 This article is freely accessible online.

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“…Obesity and metabolic dysfunction play a major role in survivors of childhood ALL leading to increased risk of morbidity and mortality throughout their life [3][4][5][6]. Altered lipid metabolism caused by intensive therapy has been addressed [7][8][9][10][11] and contradictory associations to toxicities such as thromboembolism [12][13][14][15], osteonecrosis [16,17] and pancreatitis [18][19][20][21][22][23][24] have been reported. Furthermore, abnormal lipid levels prior to ALL therapy [25][26][27][28][29] and obesity at time of ALL-diagnosis have been associated with reduced efficacy of induction therapy, impaired event-free and overall survival [30][31][32] as well as suggested as a part of the leukomogenisis [33].…”

Section: Introductionmentioning

confidence: 99%

Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

et al. 2020

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As survival of acute lymphoblastic leukemia (ALL) exceeds 90%, limiting therapy-related toxicity has become a key challenge. Cardio-metabolic dysfunction is a challenge during and after childhood ALL therapy. In a single center study, we measured triglycerides (TG), total cholesterol (TC), high (HDL) and low density lipoproteins (LDL) levels at diagnosis and assessed the association with BMI, early therapy response, on-therapy hyperlipidemia and the toxicities; thromboembolism, osteonecrosis and pancreatitis. We included 127 children (1.0-17.9 years) all treated according to the NOPHO ALL2008 protocol. Dyslipidemia was identified at ALL-diagnosis in 99% of the patients, dominated by reduced HDL levels (98%) and mild hypertriglyceridemia (61%). Hypertriglyceridemia was not associated with body mass index (P = 0.71). Five percent of patients had mild hypercholesterolemia, 14% had mild hypocholesterolemia, 13% had decreased and 1% elevated LDL-levels. Increased TG and TC levels at ALL-diagnosis were not associated with any on-therapy lipid levels. Lipid levels and BMI were not associated to MRD after induction therapy; However, BMI and hypercholesterolemia were associated with worse risk group stratification (P<0.045 for all). The cumulative incidence of thromboembolism was increased both for patients with hypo-(20.0%) and hypercholesterolemia (16.7%) compared to patients with normal TC levels (2.2%) at diagnosis (P = 0.0074). In conclusion, dyslipidemic changes were present prior to ALL-therapy in children with ALL but did not seem to affect dysmetabolic traits during therapy and were not predictive of on-therapy toxicities apart from an association between dyscholesterolemia at time of ALL-diagnosis and risk of thromboembolism. However, the latter should be interpreted with caution due to low number in the groups.

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Predictors of hepatotoxicity and pancreatitis in children and adolescents with acute lymphoblastic leukemia treated according to contemporary regimens

Abstract: Obese and/or older children are particularly at risk for hepatotoxicity and pancreatitis, and may benefit from toxicity surveillance and chemoprotective strategies to prevent or mitigate associated morbidity.

Cited by 58 publications

References 58 publications

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia

Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

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